| ORGANIC CHEMISTRY II CHEM 2325 |
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| ORGANIC CHEMISTRY II CHEM 2325 |
|
NUCLEIC ACIDS
Nucleic acids are found in the nucleus of the cell and have acidic properties.
DNA (deoxyribose nucleic acid) and RNA (ribose nucleic acid)
DNA - passes genetic traits
RNA - builds
Hydrolytic Products of DNA and RNA
DNA --> Oligionucleotides --> Mononucleotides --> Nucleosides + phosphate --> base + sugar
Sugar Components
Bases
There are two classes of bases: purine and pyrimidine
There are five common bases. Two are purine type structures and three are pyrimidine based structures.
Thymine is normally found only in DNA.
Uracil is normally found only in RNA.
Nucleoside
Nucleosides are the combination of the sugar with a base.
Each nucleoside combination of the sugar and base has a unique name.
Base RNA DNA adenine adenosine deoxyadenosine guanine guanosine deoxyguanosine uracil uridine --------------------- cytosine cytidine deoxycytidine thymine ------------- deoxythymine
Nucleotides
Nucleotides consist of a nucleoside (sugar + base) and a phosphate group attached to the 3' or the 5' position of the sugar.
NUCLEIC ACIDS
Nucleic acids can be polymerized to form a macromolecule. The monomers are the various nucleotides which are linked by the phosphate group between the 3' of one nucleoside and the 5' of the other nucleotide.
The figure above is an example of a segment of DNA. To abbreviate the sequence of nucleosides, the letters (A,T,C,G) are used instead of drawing the actual molecule since the sugars and the phosphate backbone are consistent.
Example: A-T-A-G-T-C-G-T-G-G-A-C-T-T-G etc
DNA consists of two strands of nucleic acids bonded together via hydrogen bonding between the bases. The bases involved are called base pairs. Deoxyadenosine is always paired with deoxythymine (A-T) and deoxyguanosine is always paired with deoxycytidine (G-C). This double strand has a secondary structure of an a - helix.
DNA is an extremely large polymer. The monomeric subunits from which it is built are called deoxyribonucleotides. It takes a large amount of information to code for an organism eg 3 million bases for a 'simple' bacterium and 3 thousand million for a human being. This is not a trivial problem because in the case of a human being each cell contains TWO METRES of DNA. The DNA molecule is composed of two strands which are paired with one another.
DNA-(DeoxyriboNucleic Acid) is the molecule of heredity. If a living organism is to survive then it is essential that the DNA molecule is passed onto daughter cells with the minimum of corruption. If the information in DNA becomes corrupted, ie mutations are introduced into the DNA, then the viability of the descendants is open to question. This requirement for accurate information transfer from one generation to another is the major reason for the DNA molecule being double stranded.
DNA consists of three different molecules which are covalently linked together.
These three different components are :
- a base which has a heterocyclic aromatic ring structure.
- a 5-carbon sugar (a pentose) called deoxyribose. T
- a phosphate group
The three components are linked together to form a deoxyribonucleotide triphosphate.
Initially, the base is linked (via the N-9 of purines or N-1 of pyrimidines) to the 1' carbon of the sugar deoxyribose to form a deoxyribonucleoside (deoxyadenosine, deoxyguanosine, deoxycytidine or deoxythymidine).
The next stage involves the addition of one, two or three phosphate groups to the 5' OH of deoxyribose to give deoxyribonucleotides (dATP or dGMP).
The final stage in the formation of a strand of DNA is to covalently link one deoxyribonucleotide triphosphate to another to give a polymeric molecule (a polydeoxyribonucleotide ). This is achieved by forming a phosphodiester bridge between the phosphate on the 5' OH of an incoming deoxyribonucleotide triphosphate with the 3' OH of the growing DNA strand. The DNA is synthesised in a 5' to 3' direction and has polarity (the 5' and 3' ends are different). Therefore, the sequence 5' AGCT 3' is different from the sequence 3' AGCT 5'.
It is the order of the bases in the DNA which defines the order of amino acids in a protein. The order of amino acids in a protein dictates the enzymatic or structural activity of the protein and hence the way in which an organism develops. The DNA sequence found in a cell dictates what enzymes are found there and hence what functions the cell is able to carry out.
In 1953 the structure of DNA was elucidated by John Watson and Francis Crick. They found that the ratio of adenine (A) to thymine (T) and guanine (G) to cytosine (C) was always 1:1, suggesting that A always bound with T and that G always bound with C.
Using X-ray diffraction analysis by Wilkins' group, they concluded that the structure was a double helix (like a twisted ladder), in which two chains ran in opposite directions and were linked by hydrogen bonds. In order to make the structure stable it was necessary to maintain a constant width and so a pyrimidine in one chain is always paired with a purine in the other (A pairs with T and G pairs with C).
The two strands of a DNA molecule are base paired and anti-parallel.
The base pairing rules (A pairs with T and G pairs with C) mean that the sequence in one DNA strand defines the sequence in the other.
The two strands are said to be anti-parallel (one strand ran in the 5' to 3' direction and this paired with one which ran in a 3' to 5' direction). This is the reason why DNA can act as the genetic material. When the two DNA strands separate each acts as a template for the synthesis of a new complementary DNA molecule. One of each of these two new, identical double stranded DNAs is now given to each daughter cell.
DNA Replication
Transcription refers to the enzymatic synthesis of RNA using a DNA molecule as a template. The enzyme that carries out this synthesis is known as RNA polymerase.
RNA is transcribed from only a single DNA strand.
A single stranded RNA molecule is produced which has the same SENSE as one of the DNA strands (the sense strand) and which is complementary to the other strand (the template strand).
DNA sense strand AGGTGAGTCAACACCA DNA template strand TCCACTCAGTTGTGGT RNA strand AGGAGUGUCAACACCA The product of transcription (RNA) can be one of three major types.
- messenger RNA (mRNA)
- transfer RNA (tRNA)
- ribosomal RNA (rRNA)
mRNA contains the genetic information present in DNA therefore mRNAs code for proteins. This is translated in the cytoplasm of the cell.
tRNA codes for an adapter molecule. This molecule is bifunctional and converts the base code present in DNA and RNA into the amino acid code present in proteins. The purpose of a tRNA is to help in the deciphering of the nucleotide code into an amino acid code. This takes place on a ribosome which acts as a platform on which the synthesis of protein (translation) takes place. tRNAs must be sufficiently different so that each is specific for its own amino acid but must also be sufficiently similar to fit into the same position on the ribosome. They have a constant three dimensional shape. A anticodon loop contains a sequence complementary to the codon found in the mRNA which ensures that the correct amino acid is placed at the correct position in the protein.
A typical protein contains about 20 different amino acids and its average size is 500 amino acids. The amino acids are arranged in a linear order and it is this sequence of amino acids which gives a protein its individual characteristics. Therefore, the DNA code must be able to generate at least 20 different codes with one code for each amino acid.
If one base (A, T, G or C) coded for one amino acid this could only give four different combinations (words). Two bases could not code for all the required amino acids as there could be only 16 combinations or codes. Three bases coded for an amino acids would have 64 possible combinations which is sufficient to code for 20 amino acids and the corresponding control signals (starts and stops). In practice, what is found are blocks of three bases (called a CODON) which code for each amino acid.
The ribosome reads the mRNA which consists of triplets of bases called codons. Each codon codes for a particular amino acid. This codon is matched by a complementary triplet of bases (anti-codon) the tRNA. If the two sets are complementary, the tRNA transfers in attached amino acid to the protein strand and the mRNA is moved up one set of codons and the process continues. When an area of codes are reached called the nonsense codes, the ribsome releases the completed protein.
