DNA

Functions

DNA contains the instructions needed for an organism to develop, survive and reproduce.

The order of nucleotide subunits contained in the linear sequence or primary structure of the polymers of DNA represents all of the genetic information carried by a cell.

The segment of a bases that to make a protein is known as a gene.

DNA codes for the assembly of proteins by way of a ribonucleic acid (RNA) intermediate, the messenger RNA (mRNA). But it is the interactions among the resulting proteins, other RNAs like microRNAs, and their feedback influences on the genome that will determine how cells, tissues, organs, and the body as a whole will take on its form and function.

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It is transcribed as the strands unwind and replicate.

The size of a gene may vary greatly, ranging from about 1,000 bases to 1 million bases in humans.

Genes only make up about 1 percent of the DNA sequence.

DNA sequences outside this 1 percent are involved in regulating when, how and how much of a protein is made.

[To carry out these functions, DNA sequences must be converted into messages that can be used to produce proteins, which are the complex molecules that do most of the work in our bodies.]

This is accomplished through transcription, etc etc

[The DNA of eukaryotic organisms (such as animals, plants and fungi) is stored in two cellular compartments: in the nucleus and in organelles called mitochondria, which transform nutrients into energy to allow the cell to function. The nucleus harbours most of our genes, tightly packaged into 46 chromosomes, of which half are inherited from our mother’s egg and half from our father’s sperm. By contrast, mitochondrial DNA (mtDNA) was thought to derive exclusively from maternal egg cells, with no paternal contribution1. Writing in Proceedings of the National Academy of Sciences, Luo et al.2 challenge the dogma of strict maternal mtDNA inheritance in humans, and provide compelling evidence that, in rare cases, the father might pass on his mtDNA to the offspring, after all.]

DNA

DNA accomplishes gene expression by:

1. Synthesis of a functional gene product
2. Replication

The order of the nucleotides in the DNA sequence forms the genetic code that directs the expression of genes. The specificity of the hydrogen bonding is the molecular basis of the accurate copying of the DNA sequence that is required for gene expression. Segments of strands of DNA function for gene expression. Genes correspond to regions within DNA.

These gene products are often proteins

In non-protein coding genes such as ribosomal RNA (rRNA), transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA.

Each strand can act as a template for creating a new partner strand. This is the physical method for making copies of genes that can be inherited.

Several steps in the gene expression process are regulated and modulated. These are:

Tanscription

Epigenetics

RNA splicing

Translation

Post-Translational Modification

Transciption

The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription which specifies the sequence of the amino acids within proteins.

a. Transcription

The first step that occurs is a process known as transcription. DNA is read by the (who does this) messengers that break it open into single stranded polynucleotide chains and is copied into RNA. RNA acts as a messenger to carry the information to other parts of the cell.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

There are many different types of proteins that include structural proteins, messenger proteins, enzymes and hormones. These perform various functions from forming the organs, skin and bones and the body to performing actions and functions via messengers, enzymes and hormones.

How is DNA linked to proteins?

DNA carries the codes for proteins. However, the actual protein differs a lot from the codes present on the DNA. The basic steps include:

Transcription

The first step that occurs is a process known as transcription. Here the information on the DNA is written down onto a different molecule called the RNA. This molecule acts as a messenger to carry the information to other parts of the cell.

Translation

The next step is called translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Each amino acid is formed by combining three bases on the RNA.

Modification and folding

The third step is modification and folding and structuring of the final protein and sending it to the required areas in the body.

Coding for proteins

DNA is read by the messengers that break it open into single stranded polynucleotide chains and is copied into RNA.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

Excellent Referene:http://learn.genetics.utah.edu/

Regulation of the expression of gene activity without alteration of genetic structure.1.

1. Maureen Barlow Pugh et. al., ed. 2006. Stedman's Medical Dictionary - 28th Ed. Baltimore, MD. Lippincott Williams & Wilkins. ISBN 0-7817-3390-9, ISBN 978-0-7817-3390-8. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?fxId=8&docId=13356. 4/15/2014 2:51:28 PM CDT (UTC -05:00).

Content 3

The next step is translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Proteins are created by ribosomes translating mRNA into polypeptide chains. Each amino acid is formed by combining three bases on the RNA.

c. Posttranslational modification (PTM)

This is the third step before sending it to the required areas in the body. These polypeptide chains undergo PTM, (such as folding, cutting and structuring), before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges).

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins is detected by mass spectrometry or Eastern blotting.

Glycoprotein Synthesis

The production of a secretory protein starts like any other protein. The mRNA is produced and transported to the cytosol where it interacts with a free cytosolic ribosome. The part that is produced first, the N-terminal, contains a signal sequence consisting of 6 to 12 amino acids with hydrophobic side chains. This sequence is recognised by a cytosolic protein, SRP (Signal Recognition Particle), which stops the translation and aids in the transport of the mRNA-ribosome complex to an SRP receptor found in the membrane of the endoplasmic reticulum. When it arrives at the ER, the signal sequence is transferred to the translocon, a protein-conducting channel in the membrane that allows the newlysynthesized polypeptide to be translocated to the ER lumen. The dissociation of SRP from the ribosome restores the translation of the secretory protein. The signal sequence is removed and the translation continues while the produced chain moves through the translocon (cotranslational translocation).

Implication: The excitement at this time is the emergence of genuinely viable strategies of direct relevance to novel probes of biological mechanism. These include approaches that now seem likely to yield synthetic proteins as clinical biopharmaceuticals in the near future.

DNA packs in all the genetic information and passes it on to the next generation. DNA holds the instructions for an organism's or each cell’s development and reproduction and ultimately death. Within cells DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.

In this process the DNA strands, that are tightly wound with each other, unwind and literally unzip to leave several bases without their partners on the other strand and remain along the backbone of the molecule.

The bases are very specific about which base they will attach to and the adenine only pairs with thymine and guanine will only pair with cytosine. Unpaired bases come and attach to these free bases and a new strand is formed that is complementary to the original sequence.

The end result is a strand that is a perfect match to the original one prior to it unzipping. This result in two new pairs of strands and two coiled DNA. Each of the new DNA contains one strand from the mother pair and a new one.

This is used in in reproduction, maintenance and growth of cells, tissues and body systems.

DNA replication is the process of producing two identical replicas from one original DNA molecule. It is the basis for biological inheritance. DNA is made up of two strands and each strand of the original DNA molecule serves as template for the production of the complementary strand, a process referred to as semiconservative replication. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication.

DNA replication begins at specific locations. Unwinding of DNA at the origin and synthesis of new strands results in replication forks growing bidirectionally from the origin. A number of proteins are associated with the replication fork which helps in terms of the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new DNA by adding complementary nucleotides to the template strand.

DNA replication can also be performed in vitro (artificially, outside a cell). DNA polymerases isolated from cells and artificial DNA primers can be used to initiate DNA synthesis at known sequences in a template DNA molecule. The polymerase chain reaction (PCR), a common laboratory technique, cyclically applies such artificial synthesis to amplify a specific target DNA fragment from a pool of DNA.

The pairing of complementary bases in DNA through hydrogen bonding means that the information contained within each strand is redundant. The nucleotides on a single strand can be used to reconstruct nucleotides on a newly synthesized partner strand.

The regulation of gene regulation is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. Gene regulation may also serve as a substrate for evolutionary change, since control of the timing, location, and amount of gene expression can have a profound effect on the functions (actions) of the gene in a cell or in a multicellular organism.

In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype. The genetic code stored in DNA is "interpreted" by gene expression, and the properties of the expression give rise to the organism's phenotype. Such phenotypes are often expressed by the synthesis of proteins that control the organism's shape, or that act as enzymes catalysing specific metabolic pathways characterising the organism.

DNA molecules store the blueprint of life.

Although DNA contains the genetic blueprint of life, it requires the assistance of ribonucleic acid (RNA) to be functional. RNA also consists of strands of nucleic acids joined together by sugar-phosphate bonds. Unlike DNA, RNA substitutes the nucleotide thymine (T) with uracil (U) and exists as single strands. After DNA is converted into strands of RNA, the messenger RNA (mRNA) is sent to the ribosome to direct the synthesis of proteins.

Replication

Before a cell divides it produces a new copy of each of its chromosomes. It does this during a specific part of interphase called the DNA-synthesis phase, or S phase, of the cell-division cycle; the part of interphase preceding S phase is called Gap 1, or G1, and the part following S phase is called Gap 2, or G2.

The S phase lasts for about 8 hours. By its end each chromosome has been replicated to produce two complete copies, which remain joined together at their centromeres until the M phase that soon follows. Chromosome duplication requires both the replication of the long DNA molecule in each chromosome and the assembly of a new set of chromosomal proteins onto the DNA to form chromatin.

During replication, the hydrogen bonds between nucleotides break and allow each single strand of DNA to serve as a template for replication of the other half. The two identical copies of newly synthesized of DNA are then distributed to two new daughter cells. Because during each cycle of replication half of the old DNA is preserved, DNA replication is said to be semi-conservative.

Aside: The promise and fear of genetic engineering: Would we credit a geneticist who intercalated even the most intimately analyzed base pairs into an otherwise unknown genome?

http://en.wikipedia.org/wiki/Gene_duplication

DNA replication

This helps in a variety of functions including reproduction to maintenance and growth of cells, tissues and body systems.

In this process the DNA strands, that are tightly wound with each other, unwind and literally unzip to leave several bases without their partners on the other strand and remain along the backbone of the molecule.

The bases are very specific about which base they will attach to and the adenine only pairs with thymine and guanine will only pair with cytosine. Unpaired bases come and attach to these free bases and a new strand is formed that is complementary to the original sequence.

The end result is a strand that is a perfect match to the original one prior to it unzipping. This result in two new pairs of strands and two coiled DNA. Each of the new DNA contains one strand from the mother pair and a new one.

coding for proteins and the genetic instruction guide for life and its processes. DNA holds the instructions for an organism's or each cell’s development and reproduction and ultimately death.

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Heredity

DNA packs in all the genetic information and passes it on to the next generation. DNA holds the instructions for an organism's or each cell’s development and reproduction and ultimately death.

This is accomplished throguh the process of DNA replication

In this process the DNA strands, that are tightly wound with each other, unwind and literally unzip to leave several bases without their partners on the other strand and remain along the backbone of the molecule.

The bases are very specific about which base they will attach to and the adenine only pairs with thymine and guanine will only pair with cytosine. Unpaired bases come and attach to these free bases and a new strand is formed that is complementary to the original sequence.

The end result is a strand that is a perfect match to the original one prior to it unzipping. This result in two new pairs of strands and two coiled DNA. Each of the new DNA contains one strand from the mother pair and a new one.

This is used in in reproduction, maintenance and growth of cells, tissues and body systems.

Replication 3 During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.
http://en.wikipedia.org/wiki/Gene_duplication
Transcription
Exchange or Crossover
Epigenetics

Making Protein

It is the sequence of these four nucleobases along the backbone that encodes genetic information used in the development and functioning of all known living organisms except RNA viruses. The DNA sequences have structural purposes and are also involved in regulating the use of genetic information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

Although DNA contains the genetic blueprint of life, it requires the assistance of ribonucleic acid (RNA) to be functional. After DNA is converted into strands of RNA, the messenger RNA (mRNA) is sent to the ribosome to direct the synthesis of proteins.

The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription which specifies the sequence of the amino acids within proteins.

Within cells DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.

Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA inorganelles, such as mitochondria or chloroplasts.[1] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

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For more information on DNA read the following:

1. http://en.wikipedia.org/wiki/DNA

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Animated Graphic DNA Structure: http://www.johnkyrk.com/DNAanatomy.swf ( John Kyrk Master of Biology, Harvard and Animator.)

Conccccccccccccctent 3

a. Transcription

The first step that occurs is a process known as transcription. DNA is read by the (who does this) messengers that break it open into single stranded polynucleotide chains and is copied into RNA. RNA acts as a messenger to carry the information to other parts of the cell.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

b. Translation

The next step is translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Proteins are created by ribosomes translating mRNA into polypeptide chains. Each amino acid is formed by combining three bases on the RNA.

c. Posttranslational modification (PTM)

This is the third step before sending it to the required areas in the body. These polypeptide chains undergo PTM, (such as folding, cutting and structuring), before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges).

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins is detected by mass spectrometry or Eastern blotting.

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Its function is to transcribe ribosomal RNA (rRNA) and assemble it within the cell.

while the organization and dynamics can be studied through fluorescent protein tagging and fluorescent recovery after photobleaching (FRAP). Antibodies against the PAF49 protein can also be used as a marker for the nucleolus in immunofluorescence experiments. [1]

Structure of the DNA double helix. The sugar-phosphate backbone and nitrogenous bases of each individual strand are arranged as shown. The two strands of DNA pair by hydrogen bonding between the appropriate bases to form the double-helical structure. Separation of individual strands of the DNA molecule allows DNA replication, catalyzed by DNA polymerase. As the new complementary strands of DNA are synthesized, hydrogen bonds are formed between the appropriate nitrogenous bases.

The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids, creating proteins—the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship between nucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a protein's amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole.

Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining an organism's size, the nutrition and health it experiences after inception also have a large effect.

Case 125: Pathology

Case 125

A 4-year-old boy is seen by his pediatrician for easy bruising, joint pain, and leg pain; red dots on the skin that do not blanch; and hepatosplenomegaly. The complete blood count (CBC) reveals an elevated white blood cell count (50,000/mm3), a low hemoglobin level (anemia), and thrombocytopenia (low platelet count). Examination of the peripheral smear of the blood shows numerous cells with a high nuclear to cytoplasmic ratio, and fine chromatin; the complete blood count shows anemia and thrombocytopenia.

Protein Biosynthesis
Single-stranded RNA synthesized in the nucleus copies the genetic code (transcription) and brings the message to the ribosomes, the site of protein biosynthesis. Each copied triplet represents one amino acid in the final protein. tRNA molecules, also synthesized in the nucleus, bind amino acids in accordance with the genetic code (according to the sequence of triplets) and transport them to ribosomes, where they are linked into proteins with the aid of enzymes. Each tRNA is specific for one amino acid.

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DNA structure or Nucleic Acid Structure

Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

Replication

Exchange

Epigenetics

Transcription

Translation

Post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra/extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum

Structure and function of proteins and enzymes (correlate with section on Nutrition; correlate wih section on Muscular System)

advanced (specialist level reference: http://www.cell.com/molecular-cell

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Chromosomes

These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

Within cells DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA inorganelles, such as mitochondria or chloroplasts.[1] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

03. Exchange

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For more information on DNA read the following:

1. http://en.wikipedia.org/wiki/DNA

I - Purine Nucleotides: Biosynthesis, Degradation and Salvage

A. De-novo biosynthesis of purine nucleotides

1. Inosine monophosphate synthesized de-novo by adding onto ribose - phosphate

a. First step - and regulated step - is conversion of ribose-5-phosphate to phosphoribose-1- pyrophosphate (PRPP).



b. The pyrophosphate 'activates' the C1 on the ribose for further addition:



c. Synthesis proceeds to inosine monophosphate:



Other compounds contribute to synthesis, including:
- N10-formyl THF   *******
- glycine
- glutamine
- aspartate.

2. IMP is converted to either AMP or GMP by divergent pathways

a. Converting Inosine-M-P to Adenosine-M-P:



b. Converting Inosine-M-P to Guanosine-M-P:

3. phosphorylation gives diphosphate form (nucleoside monophosphate kinases)

AMP + ATP   <-->  2ADP                     (adenylate kinase)

GMP + ATP  <--->  GDP + ADP          (guanylate kinase)

- similar enzymes specific for each nucleotide
- no specificity for ribonucleotide vs. deoxyribose.

4. deoxynucleotides formed by reduction of the sugar (ribonucleotide reductase)

     a. Free radical mechanism
     b. Hydroxyurea is a RR inhibitor
- free radical scavenger
- inhibits ribonucleotide reductase
- useful in chemotherapy

5. phosphorylation to triphosphate (nucleoside diphosphate kinase)

N1DP + N2TP  <-->  N1TP + N2DP

and

dN1DP + N2TP  <-->  dN1TP + N2DP

     - no specificity for base
     - no specificity for sugar (ribo- or deoxy- )

6. regulation of purine biosynthesis:

PRPP levels govern production of purines via feed-forward regulation
(Lots of other regulation points, but with little or no medical significance.)



Purine and Pyrimidines are a basic building block of chromosomes.

Purines - pentose, etc

Pyrimidines

Purines and pyrimidines form the Nucleis Acids - Deoxy (DNA) and RNA

DNA Forms the Chromsomes

RNA is mainkly a messenger

Chromosomes

RNA

messenger RNA

http://www.blc.arizona.edu/molecular_graphics/dna_structure/dna_tutorial.html#Components

thymine

Guanine

1. DNA Structure - This is a MUST SEE SITE by John Kyrk Master of Biology, Harvard and Animator. Animated Graphic: http://www.johnkyrk.com/DNAanatomy.swf

Deoxyribonucleic acid (DNA), is a nucleic acid polymer made of nucleotides

A nucleotide is a nucleoside with phosphate groups

DNA

These are topics in the field of Molecular Biology otherwise known as Molecular Genetics.

Structure

DNA structure or Nucleic Acid Structure

Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

Replication

Exchange

Epigenetics

Transcription

Translation

Post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra/extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum

Structure and function of proteins and enzymes (correlate with section on Nutrition; correlate wih section on Muscular System)

advanced (specialist level reference: http://www.cell.com/molecular-cell

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Backgrounder: Epigenetics and Imprinted Genes

There is far more to genetics than the sequence of building blocks in the DNA molecules that make up our genes and chromosomes. The "more" is known as epigenetics.

What is epigenetics?
Epigenetics, literally "on" genes, refers to all modifications to genes other than changes in the DNA sequence itself. Epigenetic modifications include addition of molecules, like methyl groups, to the DNA backbone. Adding these groups changes the appearance and structure of DNA, altering how a gene can interact with important interpreting (transcribing) molecules in the cell's nucleus.

How do epigenetic modifications affect genes?
Genes carry the blueprints to make proteins in the cell. The DNA sequence of a gene is transcribed into RNA, which is then translated into the sequence of a protein. Every cell in the body has the same genetic information; what makes cells, tissues and organs different is that different sets of genes are turned on or expressed.

Because they change how genes can interact with the cell's transcribing machinery, epigenetic modifications, or "marks," generally turn genes on or off, allowing or preventing the gene from being used to make a protein. On the other hand, mutations and bigger changes in the DNA sequence (like insertions or deletions) change not only the sequence of the DNA and RNA, but may affect the sequence of the protein as well. (Mutations in the sequence can prevent a gene from being recognized, amounting to its being turned off, but only if the mutations affect specific regions of the DNA.)

There are different kinds of epigenetic "marks," chemical additions to the genetic sequence. The addition of methyl groups to the DNA backbone is used on some genes to distinguish the gene copy inherited from the father and that inherited from the mother. In this situation, known as "imprinting," the marks both distinguish the gene copies and tell the cell which copy to use to make proteins.

What is "imprinting?"
"Imprinted genes" don't rely on traditional laws of Mendelian genetics, which describe the inheritance of traits as either dominant or recessive. In Mendelian genetics, both parental copies are equally likely to contribute to the outcome. The impact of an imprinted gene copy, however, depends only on which parent it was inherited from. For some imprinted genes, the cell only uses the copy from the mother to make proteins, and for others only that from the father.

Imprinting in genetics is not new, but it is gaining visibility as it is linked to more diseases and conditions that affect humans. Centuries ago, mule breeders in Iraq noted that crossing a male horse and a female donkey created a different animal than breeding a female horse and a male donkey. In the modern scientific era, however, the initial evidence for parent-of-origin effects in genetics didn't appear until the mid 1950s or so.

Then, in the mid 1980s, scientists studying mice discovered that inheritance of genetic material from both a male and a female parent was required for normal development. The experiments also revealed that the resulting abnormalities changed depending on whether the inherited genetic material was all male in origin or all female.

Around the same time, others discovered that the effects of some transgenes in mice differed when they were passed from the male or female parent. The first naturally occurring example of an imprinted gene was the discovery of imprinting in the IGF-2 gene in mice in 1991, and currently about 50 imprinted genes have been identified in mice and humans.

Why should it matter which parent donated the gene copy?
Why imprinting evolved in animals is unclear, but one hypothesis is that imprinting represents a genetic "battle of the sexes," since many imprinted genes regulate embryonic growth. Maternally-expressed imprinted genes (for which the copy from mom is always used) usually suppress growth, while paternally expressed genes usually enhance growth.

The "battle of the sexes" hypothesis is partly based on studies in animals that suggest growth-promoting imprinted genes help ensure the continuation of the father's genes, a particularly important issue for species in which more than one male can contribute to a single litter of offspring. The mother, however, is more interested in maintaining her own health, biologically speaking, and hence her genes "fight" the paternal genes and limit the size of the embryo or fetus.

What role does imprinting play in disease?
Because of their growth-related aspects, imprinted genes likely play a major role in the development of cancer and other conditions in which cell and tissue growth are abnormal. Imprinted genes in which the copy from the mother is turned on (maternally expressed) usually suppress growth, while paternally expressed genes usually stimulate growth (see above).

In cancer, some tumor suppressor genes are actually maternally expressed genes that are mistakenly turned off, preventing the growth-limiting protein from being made. Likewise, many oncogenes -- growth-promoting genes -- are paternally expressed genes for which a single dose of the protein is just right for normal cell proliferation. However, if the maternal copy of the oncogene loses its epigenetic marks and is turned on as well, uncontrolled cell growth can result.

In the collection of birth defects known as Beckwith-Wiedemann syndrome (BWS), abnormal epigenetics leads to abnormal growth of tissues, overgrowth of abdominal organs, low blood sugar at birth and cancers. Similiarly, in the imprinting disorder Prader-Willi syndrome, abnormal epigenetics causes short stature and mental retardation as well as other syndromic features.

There's also evidence in mice that some imprinted genes may play a role in behavior, particularly in nurturing and social situations.

How does imprinting get messed up?
Just as mutations in the sequence of DNA can be acquired as a cell copies its DNA, changes in a cell's epigenetics can be acquired as well, although how those errors occur isn't as well understood. Scientists do know that epigenetic alterations can be caused by environmental changes, such as the laboratory conditions used for growing cells, but the details are murky.

For example, researchers are still trying to understand the process by which cells maintain or change their gene's imprinting marks. In sperm and egg, for instance, imprinted gene copies have to be re-imprinted. Imagine one copy of a paternally imprinted gene passed from a father to his daughter (the copy is paternally inherited and will be "on") and then to her child (it's now a maternally inherited copy and will be "off").

Many scientists believe that "incorrect" epigenetic changes to tumor suppressor genes and oncogenes are some of the first steps in cancer initiation. Determining when and how imprinting marks get re-written during egg and sperm development is crucial in figuring out whether imprinting abnormalities could be corrected in cancer.

What's next for imprinting research?
As more is learned about what role abnormal imprinting plays in biology and disease, it's important to continue learning about exactly how imprinting works. What marks distinguish maternal and paternal gene copies, and are they the same for all imprinted genes? How and when during conception or formation of sperm and egg are the tell-tale marks changed? Can epigenetics be manipulated to return normal control to cells in tumors?

To find answers to these and other questions, imprinting in early stage embryos will need to be studied. Hopkins researchers recently created a mouse model in which the paternal and maternal gene copies are easily distinguished in order to help answer these questions. The true test will be one day evaluating the questions in humans, although such experiments are not currently permitted.

Deoxyribonucleic acid (DNA) is the nucleic acid involved in the genetic code. DNA sequences contain the genetic instructions used in the development and functioning of all known living organisms except RNA viruses.

DNA Structure

DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugar and phophate groups joined by ester bonds. The nucleotides are Purines and Pyrimidines.

Purines:

Pyrimidines:

http://en.wikipedia.org/wiki/Nucleotide

Animated Graphic DNA Structure: http://www.johnkyrk.com/DNAanatomy.swf This is a MUST SEE SITE by John Kyrk Master of Biology, Harvard and Animator.

These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information.

______________________________________________________

The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription which specifies the sequence of the amino acids within proteins.

Within cells DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA inorganelles, such as mitochondria or chloroplasts.[1] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

03. Exchange

xxxx

For more information on DNA read the following:

1. http://en.wikipedia.org/wiki/DNA

_______________________________________________

Replication

Before a cell divides it produces a new copy of each of its chromosomes. Iit does this during a specific part of interphase called the DNA-synthesis phase, or S phase, of the cell-division cycle; the part of interphase preceding S phase is called Gap 1, or G1, and the part following S phase is called Gap 2, or G2 (see Figure 17-3).

The S phase lasts for about 8 hours. By its end each chromosome has been replicated to produce two complete copies, which remain joined together at their centromeres until the M phase that soon follows (see Figure 8-27). Chromosome duplication requires both the replication of the long DNA molecule in each chromosome and the assembly of a new set of chromosomal proteins onto the DNA to form chromatin. In Chapter 6 we discussed the enzymology of DNA replication and described the structure of the DNA replication fork, where DNA synthesis occurs by a semi-conservative process (see Figures6-48 and 6-49). In Chapter 17 we consider how entry into the S phase is regulated as part of a more general discussion of how the cell-division cycle is controlled. In this section we describe the timing and pattern of eucaryotic chromosome replication and its relation to chromosome structure.

Humans have 23 pairs of chromosomes – a total of 46 chromosomes. Twenty-two of these pairs, called autosomes, look the same in both males and females. The 23rd pair is called the sex chromosomes and differs between males and females. Females have two copies of the X chromosome or XX, while males have one X and one Y chromosome.

Both parents have reproductive cells – sperms in fathers and ovum or eggs in mothers. These sperms and eggs contain half the number of chromosomes – 23 each. When the egg and the sperm fertilizes, this gives rise to a cell that has the complete set. Thus a person inherits half of his or her genes from each of the parents.

______________________________________________________________________

Epigenetics

Reference

http://learn.genetics.utah.edu/content/epigenetics/

-----------------------------------------------------------

Proteins

A protein is a complex molecule found in the body that is abundant and is vital for most living functions.

There are many different types of proteins that include structural proteins, messenger proteins, enzymes and hormones. These perform various functions from forming the organs, skin and bones and the body to performing actions and functions via messengers, enzymes and hormones.

How is DNA linked to proteins?

DNA carries the codes for proteins. However, the actual protein differs a lot from the codes present on the DNA. The basic steps include:

Transcription

The first step that occurs is a process known as transcription. Here the information on the DNA is written down onto a different molecule called the RNA. This molecule acts as a messenger to carry the information to other parts of the cell.

Translation

The next step is called translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Each amino acid is formed by combining three bases on the RNA.

Modification and folding

The third step is modification and folding and structuring of the final protein and sending it to the required areas in the body.

Coding for proteins

DNA is read by the messengers that break it open into single stranded polynucleotide chains and is copied into RNA.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

DNA replication

Apart from coding for proteins, DNA also replicates. This helps in a variety of functions including reproduction to maintenance and growth of cells, tissues and body systems.

In this process the DNA strands, that are tightly wound with each other, unwind and literally unzip to leave several bases without their partners on the other strand and remain along the backbone of the molecule.

The bases are very specific about which base they will attach to and the adenine only pairs with thymine and guanine will only pair with cytosine. Unpaired bases come and attach to these free bases and a new strand is formed that is complementary to the original sequence.

The end result is a strand that is a perfect match to the original one prior to it unzipping. This result in two new pairs of strands and two coiled DNA. Each of the new DNA contains one strand from the mother pair and a new one.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

coding for proteins and the genetic instruction guide for life and its processes. DNA holds the instructions for an organism's or each cell’s development and reproduction and ultimately death.

---------------------

Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides.

The order of the nucleotides in the DNA sequence forms the genetic code that directs the expression of genes. The double-stranded helix is formed as a result of hydrogen bonding between the nucleotide bases of opposite strands. The bonding is specific, such that A always pairs with T, and G always pairs with C. The specificity of the hydrogen bonding is the molecular basis of the accurate copying of the DNA sequence that is required during the processes of DNA replication (necessary for cell division) and transcription of DNA into RNA (necessary for gene expression and protein synthesis. Each strand can act as a template for creating a new partner strand. This is the physical method for making copies of genes that can be inherited.

_______________________

Its function is to transcribe ribosomal RNA (rRNA) and assemble it within the cell.

while the organization and dynamics can be studied through fluorescent protein tagging and fluorescent recovery after photobleaching (FRAP). Antibodies against the PAF49 protein can also be used as a marker for the nucleolus in immunofluorescence experiments. [1]

Structure of the DNA double helix. The sugar-phosphate backbone and nitrogenous bases of each individual strand are arranged as shown. The two strands of DNA pair by hydrogen bonding between the appropriate bases to form the double-helical structure. Separation of individual strands of the DNA molecule allows DNA replication, catalyzed by DNA polymerase. As the new complementary strands of DNA are synthesized, hydrogen bonds are formed between the appropriate nitrogenous bases.

The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids, creating proteins—the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship between nucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a protein's amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole.

Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining an organism's size, the nutrition and health it experiences after inception also have a large effect.

Case 125: Pathology

Case 125

A 4-year-old boy is seen by his pediatrician for easy bruising, joint pain, and leg pain; red dots on the skin that do not blanch; and hepatosplenomegaly. The complete blood count (CBC) reveals an elevated white blood cell count (50,000/mm3), a low hemoglobin level (anemia), and thrombocytopenia (low platelet count). Examination of the peripheral smear of the blood shows numerous cells with a high nuclear to cytoplasmic ratio, and fine chromatin; the complete blood count shows anemia and thrombocytopenia.

Protein Biosynthesis
Single-stranded RNA synthesized in the nucleus copies the genetic code (transcription) and brings the message to the ribosomes, the site of protein biosynthesis. Each copied triplet represents one amino acid in the final protein. tRNA molecules, also synthesized in the nucleus, bind amino acids in accordance with the genetic code (according to the sequence of triplets) and transport them to ribosomes, where they are linked into proteins with the aid of enzymes. Each tRNA is specific for one amino acid.

______________

DNA structure or Nucleic Acid Structure

Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

Replication

Exchange

Epigenetics

Transcription

Translation

Post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra/extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum

Structure and function of proteins and enzymes (correlate with section on Nutrition; correlate wih section on Muscular System)

advanced (specialist level reference: http://www.cell.com/molecular-cell

______________________________

Chromosomes

These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

Within cells DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA inorganelles, such as mitochondria or chloroplasts.[1] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

03. Exchange

xxxx

For more information on DNA read the following:

1. http://en.wikipedia.org/wiki/DNA

I - Purine Nucleotides: Biosynthesis, Degradation and Salvage

A. De-novo biosynthesis of purine nucleotides

1. Inosine monophosphate synthesized de-novo by adding onto ribose - phosphate

a. First step - and regulated step - is conversion of ribose-5-phosphate to phosphoribose-1- pyrophosphate (PRPP).



b. The pyrophosphate 'activates' the C1 on the ribose for further addition:



c. Synthesis proceeds to inosine monophosphate:



Other compounds contribute to synthesis, including:
- N10-formyl THF   *******
- glycine
- glutamine
- aspartate.

2. IMP is converted to either AMP or GMP by divergent pathways

a. Converting Inosine-M-P to Adenosine-M-P:



b. Converting Inosine-M-P to Guanosine-M-P:

3. phosphorylation gives diphosphate form (nucleoside monophosphate kinases)

AMP + ATP   <-->  2ADP                     (adenylate kinase)

GMP + ATP  <--->  GDP + ADP          (guanylate kinase)

- similar enzymes specific for each nucleotide
- no specificity for ribonucleotide vs. deoxyribose.

4. deoxynucleotides formed by reduction of the sugar (ribonucleotide reductase)

     a. Free radical mechanism
     b. Hydroxyurea is a RR inhibitor
- free radical scavenger
- inhibits ribonucleotide reductase
- useful in chemotherapy

5. phosphorylation to triphosphate (nucleoside diphosphate kinase)

N1DP + N2TP  <-->  N1TP + N2DP

and

dN1DP + N2TP  <-->  dN1TP + N2DP

     - no specificity for base
     - no specificity for sugar (ribo- or deoxy- )

6. regulation of purine biosynthesis:

PRPP levels govern production of purines via feed-forward regulation
(Lots of other regulation points, but with little or no medical significance.)



Purine and Pyrimidines are a basic building block of chromosomes.

Purines - pentose, etc

Pyrimidines

Purines and pyrimidines form the Nucleis Acids - Deoxy (DNA) and RNA

DNA Forms the Chromsomes

RNA is mainkly a messenger

Chromosomes

RNA

messenger RNA

http://www.blc.arizona.edu/molecular_graphics/dna_structure/dna_tutorial.html#Components

thymine

Guanine

1. DNA Structure - This is a MUST SEE SITE by John Kyrk Master of Biology, Harvard and Animator. Animated Graphic: http://www.johnkyrk.com/DNAanatomy.swf

Deoxyribonucleic acid (DNA), is a nucleic acid polymer made of nucleotides

A nucleotide is a nucleoside with phosphate groups

DNA

These are topics in the field of Molecular Biology otherwise known as Molecular Genetics.

Structure

DNA structure or Nucleic Acid Structure

Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

Replication

Exchange

Epigenetics

Transcription

Translation

Post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra/extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum

Structure and function of proteins and enzymes (correlate with section on Nutrition; correlate wih section on Muscular System)

advanced (specialist level reference: http://www.cell.com/molecular-cell

--------------------------------------

Backgrounder: Epigenetics and Imprinted Genes

There is far more to genetics than the sequence of building blocks in the DNA molecules that make up our genes and chromosomes. The "more" is known as epigenetics.

What is epigenetics?
Epigenetics, literally "on" genes, refers to all modifications to genes other than changes in the DNA sequence itself. Epigenetic modifications include addition of molecules, like methyl groups, to the DNA backbone. Adding these groups changes the appearance and structure of DNA, altering how a gene can interact with important interpreting (transcribing) molecules in the cell's nucleus.

How do epigenetic modifications affect genes?
Genes carry the blueprints to make proteins in the cell. The DNA sequence of a gene is transcribed into RNA, which is then translated into the sequence of a protein. Every cell in the body has the same genetic information; what makes cells, tissues and organs different is that different sets of genes are turned on or expressed.

Because they change how genes can interact with the cell's transcribing machinery, epigenetic modifications, or "marks," generally turn genes on or off, allowing or preventing the gene from being used to make a protein. On the other hand, mutations and bigger changes in the DNA sequence (like insertions or deletions) change not only the sequence of the DNA and RNA, but may affect the sequence of the protein as well. (Mutations in the sequence can prevent a gene from being recognized, amounting to its being turned off, but only if the mutations affect specific regions of the DNA.)

There are different kinds of epigenetic "marks," chemical additions to the genetic sequence. The addition of methyl groups to the DNA backbone is used on some genes to distinguish the gene copy inherited from the father and that inherited from the mother. In this situation, known as "imprinting," the marks both distinguish the gene copies and tell the cell which copy to use to make proteins.

What is "imprinting?"
"Imprinted genes" don't rely on traditional laws of Mendelian genetics, which describe the inheritance of traits as either dominant or recessive. In Mendelian genetics, both parental copies are equally likely to contribute to the outcome. The impact of an imprinted gene copy, however, depends only on which parent it was inherited from. For some imprinted genes, the cell only uses the copy from the mother to make proteins, and for others only that from the father.

Imprinting in genetics is not new, but it is gaining visibility as it is linked to more diseases and conditions that affect humans. Centuries ago, mule breeders in Iraq noted that crossing a male horse and a female donkey created a different animal than breeding a female horse and a male donkey. In the modern scientific era, however, the initial evidence for parent-of-origin effects in genetics didn't appear until the mid 1950s or so.

Then, in the mid 1980s, scientists studying mice discovered that inheritance of genetic material from both a male and a female parent was required for normal development. The experiments also revealed that the resulting abnormalities changed depending on whether the inherited genetic material was all male in origin or all female.

Around the same time, others discovered that the effects of some transgenes in mice differed when they were passed from the male or female parent. The first naturally occurring example of an imprinted gene was the discovery of imprinting in the IGF-2 gene in mice in 1991, and currently about 50 imprinted genes have been identified in mice and humans.

Why should it matter which parent donated the gene copy?
Why imprinting evolved in animals is unclear, but one hypothesis is that imprinting represents a genetic "battle of the sexes," since many imprinted genes regulate embryonic growth. Maternally-expressed imprinted genes (for which the copy from mom is always used) usually suppress growth, while paternally expressed genes usually enhance growth.

The "battle of the sexes" hypothesis is partly based on studies in animals that suggest growth-promoting imprinted genes help ensure the continuation of the father's genes, a particularly important issue for species in which more than one male can contribute to a single litter of offspring. The mother, however, is more interested in maintaining her own health, biologically speaking, and hence her genes "fight" the paternal genes and limit the size of the embryo or fetus.

What role does imprinting play in disease?
Because of their growth-related aspects, imprinted genes likely play a major role in the development of cancer and other conditions in which cell and tissue growth are abnormal. Imprinted genes in which the copy from the mother is turned on (maternally expressed) usually suppress growth, while paternally expressed genes usually stimulate growth (see above).

In cancer, some tumor suppressor genes are actually maternally expressed genes that are mistakenly turned off, preventing the growth-limiting protein from being made. Likewise, many oncogenes -- growth-promoting genes -- are paternally expressed genes for which a single dose of the protein is just right for normal cell proliferation. However, if the maternal copy of the oncogene loses its epigenetic marks and is turned on as well, uncontrolled cell growth can result.

In the collection of birth defects known as Beckwith-Wiedemann syndrome (BWS), abnormal epigenetics leads to abnormal growth of tissues, overgrowth of abdominal organs, low blood sugar at birth and cancers. Similiarly, in the imprinting disorder Prader-Willi syndrome, abnormal epigenetics causes short stature and mental retardation as well as other syndromic features.

There's also evidence in mice that some imprinted genes may play a role in behavior, particularly in nurturing and social situations.

How does imprinting get messed up?
Just as mutations in the sequence of DNA can be acquired as a cell copies its DNA, changes in a cell's epigenetics can be acquired as well, although how those errors occur isn't as well understood. Scientists do know that epigenetic alterations can be caused by environmental changes, such as the laboratory conditions used for growing cells, but the details are murky.

For example, researchers are still trying to understand the process by which cells maintain or change their gene's imprinting marks. In sperm and egg, for instance, imprinted gene copies have to be re-imprinted. Imagine one copy of a paternally imprinted gene passed from a father to his daughter (the copy is paternally inherited and will be "on") and then to her child (it's now a maternally inherited copy and will be "off").

Many scientists believe that "incorrect" epigenetic changes to tumor suppressor genes and oncogenes are some of the first steps in cancer initiation. Determining when and how imprinting marks get re-written during egg and sperm development is crucial in figuring out whether imprinting abnormalities could be corrected in cancer.

What's next for imprinting research?
As more is learned about what role abnormal imprinting plays in biology and disease, it's important to continue learning about exactly how imprinting works. What marks distinguish maternal and paternal gene copies, and are they the same for all imprinted genes? How and when during conception or formation of sperm and egg are the tell-tale marks changed? Can epigenetics be manipulated to return normal control to cells in tumors?

To find answers to these and other questions, imprinting in early stage embryos will need to be studied. Hopkins researchers recently created a mouse model in which the paternal and maternal gene copies are easily distinguished in order to help answer these questions. The true test will be one day evaluating the questions in humans, although such experiments are not currently permitted.

Nucleotides

The nucleotides are

thymine

Guanine

Functions

Nucleotides form the building blocks of nucleic acids (DNA and RNA) and serve to carry packets of energy within the cell (ATP). In the form of the nucleoside triphosphates (ATP, GTP, CTP and UTP), nucleotides play central roles in metabolism.[1]

In addition, nucleotides participate in cell signaling (cGMP and cAMP), and are incorporated into important cofactors of enzymatic reactions (e.g. coenzyme A, FAD, FMN, NAD, and NADP+).

Reference

1. http://en.wikipedia.org/wiki/Nucleotide

http://www.blc.arizona.edu/molecular_graphics/dna_structure/dna_tutorial.html#Components

-------------------------------------

Replication

Exchange

Epigenetics

Transcription

Translation

Post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra/extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum

Structure and function of proteins and enzymes (correlate with section on Nutrition; correlate wih section on Muscular System)

advanced (specialist level reference: http://www.cell.com/molecular-cell

______________________________

Chromosomes

These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

Within cells DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA inorganelles, such as mitochondria or chloroplasts.[1] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

03. Exchange

xxxx

For more information on DNA read the following:

1. http://en.wikipedia.org/wiki/DNA

I - Purine Nucleotides: Biosynthesis, Degradation and Salvage

A. De-novo biosynthesis of purine nucleotides

1. Inosine monophosphate synthesized de-novo by adding onto ribose - phosphate

a. First step - and regulated step - is conversion of ribose-5-phosphate to phosphoribose-1- pyrophosphate (PRPP).



b. The pyrophosphate 'activates' the C1 on the ribose for further addition:



c. Synthesis proceeds to inosine monophosphate:



Other compounds contribute to synthesis, including:
- N10-formyl THF   *******
- glycine
- glutamine
- aspartate.

2. IMP is converted to either AMP or GMP by divergent pathways

a. Converting Inosine-M-P to Adenosine-M-P:



b. Converting Inosine-M-P to Guanosine-M-P:

3. phosphorylation gives diphosphate form (nucleoside monophosphate kinases)

AMP + ATP   <-->  2ADP                     (adenylate kinase)

GMP + ATP  <--->  GDP + ADP          (guanylate kinase)

- similar enzymes specific for each nucleotide
- no specificity for ribonucleotide vs. deoxyribose.

4. deoxynucleotides formed by reduction of the sugar (ribonucleotide reductase)

     a. Free radical mechanism
     b. Hydroxyurea is a RR inhibitor
- free radical scavenger
- inhibits ribonucleotide reductase
- useful in chemotherapy

5. phosphorylation to triphosphate (nucleoside diphosphate kinase)

N1DP + N2TP  <-->  N1TP + N2DP

and

dN1DP + N2TP  <-->  dN1TP + N2DP

     - no specificity for base
     - no specificity for sugar (ribo- or deoxy- )

6. regulation of purine biosynthesis:

PRPP levels govern production of purines via feed-forward regulation
(Lots of other regulation points, but with little or no medical significance.)



Purine and Pyrimidines are a basic building block of chromosomes.

Purines - pentose, etc

Pyrimidines

Purines and pyrimidines form the Nucleis Acids - Deoxy (DNA) and RNA

DNA Forms the Chromsomes

RNA is mainkly a messenger

Chromosomes

RNA

messenger RNA

http://www.blc.arizona.edu/molecular_graphics/dna_structure/dna_tutorial.html#Components

thymine

Guanine

1. DNA Structure - This is a MUST SEE SITE by John Kyrk Master of Biology, Harvard and Animator. Animated Graphic: http://www.johnkyrk.com/DNAanatomy.swf

Deoxyribonucleic acid (DNA), is a nucleic acid polymer made of nucleotides

A nucleotide is a nucleoside with phosphate groups

DNA

These are topics in the field of Molecular Biology otherwise known as Molecular Genetics.

Structure

DNA structure or Nucleic Acid Structure

Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

Replication

Exchange

Epigenetics

Transcription

Translation

Post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra/extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum

Structure and function of proteins and enzymes (correlate with section on Nutrition; correlate wih section on Muscular System)

advanced (specialist level reference: http://www.cell.com/molecular-cell

--------------------------------------

Backgrounder: Epigenetics and Imprinted Genes

There is far more to genetics than the sequence of building blocks in the DNA molecules that make up our genes and chromosomes. The "more" is known as epigenetics.

What is epigenetics?
Epigenetics, literally "on" genes, refers to all modifications to genes other than changes in the DNA sequence itself. Epigenetic modifications include addition of molecules, like methyl groups, to the DNA backbone. Adding these groups changes the appearance and structure of DNA, altering how a gene can interact with important interpreting (transcribing) molecules in the cell's nucleus.

How do epigenetic modifications affect genes?
Genes carry the blueprints to make proteins in the cell. The DNA sequence of a gene is transcribed into RNA, which is then translated into the sequence of a protein. Every cell in the body has the same genetic information; what makes cells, tissues and organs different is that different sets of genes are turned on or expressed.

Because they change how genes can interact with the cell's transcribing machinery, epigenetic modifications, or "marks," generally turn genes on or off, allowing or preventing the gene from being used to make a protein. On the other hand, mutations and bigger changes in the DNA sequence (like insertions or deletions) change not only the sequence of the DNA and RNA, but may affect the sequence of the protein as well. (Mutations in the sequence can prevent a gene from being recognized, amounting to its being turned off, but only if the mutations affect specific regions of the DNA.)

There are different kinds of epigenetic "marks," chemical additions to the genetic sequence. The addition of methyl groups to the DNA backbone is used on some genes to distinguish the gene copy inherited from the father and that inherited from the mother. In this situation, known as "imprinting," the marks both distinguish the gene copies and tell the cell which copy to use to make proteins.

What is "imprinting?"
"Imprinted genes" don't rely on traditional laws of Mendelian genetics, which describe the inheritance of traits as either dominant or recessive. In Mendelian genetics, both parental copies are equally likely to contribute to the outcome. The impact of an imprinted gene copy, however, depends only on which parent it was inherited from. For some imprinted genes, the cell only uses the copy from the mother to make proteins, and for others only that from the father.

Imprinting in genetics is not new, but it is gaining visibility as it is linked to more diseases and conditions that affect humans. Centuries ago, mule breeders in Iraq noted that crossing a male horse and a female donkey created a different animal than breeding a female horse and a male donkey. In the modern scientific era, however, the initial evidence for parent-of-origin effects in genetics didn't appear until the mid 1950s or so.

Then, in the mid 1980s, scientists studying mice discovered that inheritance of genetic material from both a male and a female parent was required for normal development. The experiments also revealed that the resulting abnormalities changed depending on whether the inherited genetic material was all male in origin or all female.

Around the same time, others discovered that the effects of some transgenes in mice differed when they were passed from the male or female parent. The first naturally occurring example of an imprinted gene was the discovery of imprinting in the IGF-2 gene in mice in 1991, and currently about 50 imprinted genes have been identified in mice and humans.

Why should it matter which parent donated the gene copy?
Why imprinting evolved in animals is unclear, but one hypothesis is that imprinting represents a genetic "battle of the sexes," since many imprinted genes regulate embryonic growth. Maternally-expressed imprinted genes (for which the copy from mom is always used) usually suppress growth, while paternally expressed genes usually enhance growth.

The "battle of the sexes" hypothesis is partly based on studies in animals that suggest growth-promoting imprinted genes help ensure the continuation of the father's genes, a particularly important issue for species in which more than one male can contribute to a single litter of offspring. The mother, however, is more interested in maintaining her own health, biologically speaking, and hence her genes "fight" the paternal genes and limit the size of the embryo or fetus.

What role does imprinting play in disease?
Because of their growth-related aspects, imprinted genes likely play a major role in the development of cancer and other conditions in which cell and tissue growth are abnormal. Imprinted genes in which the copy from the mother is turned on (maternally expressed) usually suppress growth, while paternally expressed genes usually stimulate growth (see above).

In cancer, some tumor suppressor genes are actually maternally expressed genes that are mistakenly turned off, preventing the growth-limiting protein from being made. Likewise, many oncogenes -- growth-promoting genes -- are paternally expressed genes for which a single dose of the protein is just right for normal cell proliferation. However, if the maternal copy of the oncogene loses its epigenetic marks and is turned on as well, uncontrolled cell growth can result.

In the collection of birth defects known as Beckwith-Wiedemann syndrome (BWS), abnormal epigenetics leads to abnormal growth of tissues, overgrowth of abdominal organs, low blood sugar at birth and cancers. Similiarly, in the imprinting disorder Prader-Willi syndrome, abnormal epigenetics causes short stature and mental retardation as well as other syndromic features.

There's also evidence in mice that some imprinted genes may play a role in behavior, particularly in nurturing and social situations.

How does imprinting get messed up?
Just as mutations in the sequence of DNA can be acquired as a cell copies its DNA, changes in a cell's epigenetics can be acquired as well, although how those errors occur isn't as well understood. Scientists do know that epigenetic alterations can be caused by environmental changes, such as the laboratory conditions used for growing cells, but the details are murky.

For example, researchers are still trying to understand the process by which cells maintain or change their gene's imprinting marks. In sperm and egg, for instance, imprinted gene copies have to be re-imprinted. Imagine one copy of a paternally imprinted gene passed from a father to his daughter (the copy is paternally inherited and will be "on") and then to her child (it's now a maternally inherited copy and will be "off").

Many scientists believe that "incorrect" epigenetic changes to tumor suppressor genes and oncogenes are some of the first steps in cancer initiation. Determining when and how imprinting marks get re-written during egg and sperm development is crucial in figuring out whether imprinting abnormalities could be corrected in cancer.

What's next for imprinting research?
As more is learned about what role abnormal imprinting plays in biology and disease, it's important to continue learning about exactly how imprinting works. What marks distinguish maternal and paternal gene copies, and are they the same for all imprinted genes? How and when during conception or formation of sperm and egg are the tell-tale marks changed? Can epigenetics be manipulated to return normal control to cells in tumors?

To find answers to these and other questions, imprinting in early stage embryos will need to be studied. Hopkins researchers recently created a mouse model in which the paternal and maternal gene copies are easily distinguished in order to help answer these questions. The true test will be one day evaluating the questions in humans, although such experiments are not currently permitted.

Heredity

Production of Proteins

Cell Reproduction

These molecules store the blueprint of life.

The chemical structures of the four nucleotides are planar due to the delocalized electrons in the five- and six-membered rings, each having a thickness of 3.4 angstroms. When the nucleotides form the double helix structure, A-T and G-C are joined together by a hydrogen bond to form a base pair. The base pairs are then joined together by sugar bonds to form the helix. X-ray data shows that there are 10 base pairs per turn of the helix.

The helical model of DNA also explains the theory of genetic replication. James Watson once described it as the "pretty molecule" because the method of replication is so self evident in this structure. During replication, the hydrogen bonds between nucleotides break and allow each single strand of DNA to serve as a template for replication of the other half. The two identical copies of newly synthesized of DNA are then distributed to two new daughter cells. Because during each cycle of replication half of the old DNA is preserved, DNA replication is said to be semi-conservative.

Although DNA contains the genetic blueprint of life, it requires the assistance of ribonucleic acid (RNA) to be functional. RNA also consists of strands of nucleic acids joined together by sugar-phosphate bonds. Unlike DNA, RNA substitutes the nucleotide thymine (T) with uracil (U) and exists as single strands. After DNA is converted into strands of RNA, the messenger RNA (mRNA) is sent to the ribosome to direct the synthesis of proteins.

Would we credit a geneticist who intercalated even the most intimately analyzed base pairs into an otherwise unknown genome?

DNA packs in all the genetic information and passes it on to the next generation. DNA holds the instructions for an organism's or each cell’s development and reproduction and ultimately death.

This is accomplished throguh the process of DNA replication

In this process the DNA strands, that are tightly wound with each other, unwind and literally unzip to leave several bases without their partners on the other strand and remain along the backbone of the molecule.

The bases are very specific about which base they will attach to and the adenine only pairs with thymine and guanine will only pair with cytosine. Unpaired bases come and attach to these free bases and a new strand is formed that is complementary to the original sequence.

The end result is a strand that is a perfect match to the original one prior to it unzipping. This result in two new pairs of strands and two coiled DNA. Each of the new DNA contains one strand from the mother pair and a new one.

This is used in in reproduction, maintenance and growth of cells, tissues and body systems.

Replication 3 During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.
http://en.wikipedia.org/wiki/Gene_duplication

Transcription

Exchange or Crossover

Epigenetics

Conccccccccccccctent 3

a. Transcription

The first step that occurs is a process known as transcription. DNA is read by the (who does this) messengers that break it open into single stranded polynucleotide chains and is copied into RNA. RNA acts as a messenger to carry the information to other parts of the cell.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

b. Translation

The next step is translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Proteins are created by ribosomes translating mRNA into polypeptide chains. Each amino acid is formed by combining three bases on the RNA.

c. Posttranslational modification (PTM)

This is the third step before sending it to the required areas in the body. These polypeptide chains undergo PTM, (such as folding, cutting and structuring), before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges).

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins is detected by mass spectrometry or Eastern blotting.

The DNA functions for gene expression.

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product.

These products are often proteins

in non-protein coding genes such as ribosomal RNA (rRNA), transfer RNA (tRNA) or small nuclear RNA (snRNA) genes, the product is a functional RNA.

The process of gene expression is used by all known life - eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses - to generate the macromolecular machinery for life.

Several steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-translational modification of a protein.

Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. Gene regulation may also serve as a substrate for evolutionary change, since control of the timing, location, and amount of gene expression can have a profound effect on the functions (actions) of the gene in a cell or in a multicellular organism.

In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype. The genetic code stored in DNA is "interpreted" by gene expression, and the properties of the expression give rise to the organism's phenotype. Such phenotypes are often expressed by the synthesis of proteins that control the organism's shape, or that act as enzymes catalysing specific metabolic pathways characterising the organism.

See: Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

Heredity

Production of Proteins

Cell Reproduction

These molecules store the blueprint of life.

The chemical structures of the four nucleotides are planar due to the delocalized electrons in the five- and six-membered rings, each having a thickness of 3.4 angstroms. When the nucleotides form the double helix structure, A-T and G-C are joined together by a hydrogen bond to form a base pair. The base pairs are then joined together by sugar bonds to form the helix. X-ray data shows that there are 10 base pairs per turn of the helix.

The helical model of DNA also explains the theory of genetic replication. James Watson once described it as the "pretty molecule" because the method of replication is so self evident in this structure. During replication, the hydrogen bonds between nucleotides break and allow each single strand of DNA to serve as a template for replication of the other half. The two identical copies of newly synthesized of DNA are then distributed to two new daughter cells. Because during each cycle of replication half of the old DNA is preserved, DNA replication is said to be semi-conservative.

Although DNA contains the genetic blueprint of life, it requires the assistance of ribonucleic acid (RNA) to be functional. RNA also consists of strands of nucleic acids joined together by sugar-phosphate bonds. Unlike DNA, RNA substitutes the nucleotide thymine (T) with uracil (U) and exists as single strands. After DNA is converted into strands of RNA, the messenger RNA (mRNA) is sent to the ribosome to direct the synthesis of proteins.

Would we credit a geneticist who intercalated even the most intimately analyzed base pairs into an otherwise unknown genome?

DNA packs in all the genetic information and passes it on to the next generation. DNA holds the instructions for an organism's or each cell’s development and reproduction and ultimately death.

This is accomplished throguh the process of DNA replication

In this process the DNA strands, that are tightly wound with each other, unwind and literally unzip to leave several bases without their partners on the other strand and remain along the backbone of the molecule.

The bases are very specific about which base they will attach to and the adenine only pairs with thymine and guanine will only pair with cytosine. Unpaired bases come and attach to these free bases and a new strand is formed that is complementary to the original sequence.

The end result is a strand that is a perfect match to the original one prior to it unzipping. This result in two new pairs of strands and two coiled DNA. Each of the new DNA contains one strand from the mother pair and a new one.

This is used in in reproduction, maintenance and growth of cells, tissues and body systems.

Replication 3 During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes.
http://en.wikipedia.org/wiki/Gene_duplication

Transcription

Exchange or Crossover

Epigenetics

Conccccccccccccctent 3

a. Transcription

The first step that occurs is a process known as transcription. DNA is read by the (who does this) messengers that break it open into single stranded polynucleotide chains and is copied into RNA. RNA acts as a messenger to carry the information to other parts of the cell.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

b. Translation

The next step is translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Proteins are created by ribosomes translating mRNA into polypeptide chains. Each amino acid is formed by combining three bases on the RNA.

c. Posttranslational modification (PTM)

This is the third step before sending it to the required areas in the body. These polypeptide chains undergo PTM, (such as folding, cutting and structuring), before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges).

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins is detected by mass spectrometry or Eastern blotting.

Glycoprotein Synthesis

The production of a secretory protein starts like any other protein. The mRNA is produced and transported to the cytosol where it interacts with a free cytosolic ribosome. The part that is produced first, the N-terminal, contains a signal sequence consisting of 6 to 12 amino acids with hydrophobic side chains. This sequence is recognised by a cytosolic protein, SRP (Signal Recognition Particle), which stops the translation and aids in the transport of the mRNA-ribosome complex to an SRP receptor found in the membrane of the endoplasmic reticulum. When it arrives at the ER, the signal sequence is transferred to the translocon, a protein-conducting channel in the membrane that allows the newlysynthesized polypeptide to be translocated to the ER lumen. The dissociation of SRP from the ribosome restores the translation of the secretory protein. The signal sequence is removed and the translation continues while the produced chain moves through the translocon (cotranslational translocation).

Implication: The excitement at this time is the emergence of genuinely viable strategies of direct
relevance to novel probes of biological mechanism. These include approaches that now seem likely to yield synthetic proteins as clinical biopharmaceuticals in the near future.

_______________________________________a. Transcription

The first step that occurs is a process known as transcription. DNA is read by the (who does this) messengers that break it open into single stranded polynucleotide chains and is copied into RNA. RNA acts as a messenger to carry the information to other parts of the cell.

RNA forms opposite bases from that present on the DNA. For example, G on the DNA forms C on the RNA strand.

Each of the bases gets together in threes and these form particular amino acids. There are 20 such amino acids. These are also known as the building blocks of proteins.

The amino acids first form a long chain called the polypeptide chain. This polypeptide chain undergoes conformational and structural changes and folds and refolds over itself to form the final complex structure of the protein.

b. Translation

The next step is translation. In this step the cell organelles called ribosomes come into play. These ribosomes act as translators by translating the messenger's code into the proper protein format or a chain of amino acids that form the building blocks of the protein. Proteins are created by ribosomes translating mRNA into polypeptide chains. Each amino acid is formed by combining three bases on the RNA.

c. Posttranslational modification (PTM)

This is the third step before sending it to the required areas in the body. These polypeptide chains undergo PTM, (such as folding, cutting and structuring), before becoming the mature protein product.

Posttranslational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

A protein (also called a polypeptide) is a chain of amino acids. During protein synthesis, 20 different amino acids can be incorporated to become a protein. After translation, the posttranslational modification of amino acids extends the range of functions of the protein by attaching it to other biochemical functional groups (such as acetate, phosphate, various lipids and carbohydrates), changing the chemical nature of an amino acid (e.g. citrullination), or making structural changes (e.g. formation of disulfide bridges).

Also, enzymes may remove amino acids from the amino end of the protein, or cut the peptide chain in the middle. For instance, the peptide hormone insulin is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Also, most nascent polypeptides start with the amino acid methionine because the "start" codon on mRNA also codes for this amino acid. This amino acid is usually taken off during post-translational modification.

Other modifications, like phosphorylation, are part of common mechanisms for controlling the behavior of a protein, for instance activating or inactivating an enzyme.

Post-translational modification of proteins is detected by mass spectrometry or Eastern blotting.

Glycoprotein Synthesis

The production of a secretory protein starts like any other protein. The mRNA is produced and transported to the cytosol where it interacts with a free cytosolic ribosome. The part that is produced first, the N-terminal, contains a signal sequence consisting of 6 to 12 amino acids with hydrophobic side chains. This sequence is recognised by a cytosolic protein, SRP (Signal Recognition Particle), which stops the translation and aids in the transport of the mRNA-ribosome complex to an SRP receptor found in the membrane of the endoplasmic reticulum. When it arrives at the ER, the signal sequence is transferred to the translocon, a protein-conducting channel in the membrane that allows the newlysynthesized polypeptide to be translocated to the ER lumen. The dissociation of SRP from the ribosome restores the translation of the secretory protein. The signal sequence is removed and the translation continues while the produced chain moves through the translocon (cotranslational translocation).

Implication: The excitement at this time is the emergence of genuinely viable strategies of direct
relevance to novel probes of biological mechanism. These include approaches that now seem likely to yield synthetic proteins as clinical biopharmaceuticals in the near future.

References

1. See: Gene Expression *

http://www.johnkyrk.com/er.swf (This is a graphic animated Illustration of gene expression)

2. DNA structure (see: Nucleic Acid Structure which includes RNA

http://en.wikipedia.org/wiki/Epigenetics#Medicine EPIGENETICS