Chapter 3.
The Nucleic Acids
Originally isolated from nucleus of eukaryotic cells.
Are long linear polymers-storing the GI.
Nuclein- A novel phosphorous bearing substance in the nuclei of WBC.
- Mostly chromatin, which is a complex of DNA and
chromosomal protein
Two types of NAs
DNA- Master copy of each cell's genome
-Contains all infos. Needed by the cell to live and propagate.
- long molecule with many thousand genes
RNA- Transformation of GI to cell machinery
- much shorter
- Carry only one or a few genes.
3.1. The Chemical Nature of DNA and RNA
The nucleic acids (DNA and RNA) – are linear polymers made of
Subunits known as nucleotides.
Determination of Info. In each gene is done by the order of different
nucleotides.
Four different types of Nucleotide found in each type of nucleic acid
(NA).
Three Parts of Nucleotide:
1) A cyclic five-carbon sugar (pentose)
-Called Ribose in RNA
- Deoxyribose in DNA- lacking oxygen at C2'.
The Chemical structure of Pentose-The five carbon
atoms labeled as C1′ to C5′. Ring with four C atom and
oxygen and the 5th C-forms side chain to the ring
2) Base= Nitrogenous Base
• Five types:
- Adenine (A)
- Cytosine (C)
- Guanine (G)
- Thymine (T)- in DNA }
genetically
equivalent
- Uracil (U)- in RNA }
Two types of Bases in NAs
Pyrimidines
-Derivatives of heterocyclic compounds=pyrimidine
- Contains a single ring
- Are Cytosine, Thymine and Uracil: differ in the types and
position of chemical groups attached to the ring.
Major Pyrimidines
in DNA – Thymine and cytosine
in RNA- Uracil and cytosine
Purines
-Derivatives of The fused-ring compounds=Purine
-Contain a fused double ring
- Are Adenine and Guanine- also differ in types and
positions of chemical groups attached to the purine ring
Basic structure of Pyrimidines and Purines
Description of Major pyrimidine bases of nucleic acids
-Cytosine is 2-oxy-4 aminopyrimidine
-Thymine is 5-methyl-2,4-dioyxpyrimidine
-Uracil is 2,4-dioxypyrimidine
Description of Major purine bases of nucleic acids
- Adenine is 6-amino purine
-Guanine is 6-oxy-2-amino purine
3) A Phosphate -attached to the 5′Carbon of the sugar by
Phoshodiester linkage
-Responsible for the strong negative charge both in
Nucleotides and NAs
Nucleosides: A base (Pyrimidine or purine) linked to a sugar (Ribose or
Deoxyribose).
Thus-the name -Ribonucleosides
- Deoxyribonucleosides
Purine nucleosides have β-glycosidic linkage from N-9 of the base to C1′of the
sugar.
Pyrimidine nucleotides have the linkage from N1 of the base to C1′ of the sugar.
The names of the nucleosides correspond to the name of the base, whereas the
name of nucleotides are referred to as phosphate derivatives of the corresponding
nucleosides E.g., Nucleosides of adenine is AMP
base
sugar
nucleoside
nucleotides (nucleoside mono-, di-, and triphosphates)
Some minor purine bases, shown as the
nucleosides.
Nucleotides:
• In a nucleic acid chain, two nucleotides are linked by a
phosphodiester bond, which may be formed by the
condensation reaction) similar to the formation of the
peptide bond.
• In cells, such process has been found in the ligation
between two nucleic acid fragments.
• However, the whole nucleic acid chain is usually
synthesized by RNA polymerase or DNA polymerase.
Fig. Formation of the phosphodiester bond through the
condensation reaction.
-An ester is a compound formed from an alcohol (bearing hydroxyl
group) and an acid.
-In nucleotides- the alcohol group is 5′-hydroxyl of the sugar & the acid
is Phosphoric acid, hence the name phosphoester.
• The phosphate is esterified to both the 3′ and 5′ carbon atoms
, the overall structure is therefore called phosphodiester
linkage.
- The Phosphate group linking the sugar has a negative charge.
- The phosphate groups and sugars for the back bone of each
strand of DNA or RNA.
- The bases are joined to the sugars and stick out sideways.
Structure of Polynucleotide- Bases are attached to Deoxyribose- it is a DNA
nucleotide
At the phoshodiester linkage there is a free rotation.
The N-glycosylic bond between a base and the sugar
allows the base to rotate freely.
The linkage is repeated many times building a large
structure- a chain or strands having hundreds or millions of
nucleotide within a single giant molecule.
• cConCc’
The a nucleic acid chain also has orientation:
its 5' end contains a free phosphate group and
3' end contains a free hydroxyl
group. Synthesis of a nucleic acid chain
always proceeds from 5' to 3'. Therefore,
unless specified otherwise, the sequence of a
nucleic acid chain is written from 5' to 3' (left to right).
A nucleic acid chain. Its 5' end contains a free phosphate group. The 3' end has a free
hydroxyl group.
In DNA or RNA, a nucleic acid chain is also called a
strand. A DNA molecule typically contains two strands
whereas most RNA molecules contain a single strand.
-Thelength of a nucleic acid chain is represented by the
number of bases. In the case of a double-stranded
nucleic acid, bases are paired between two strands.
-Therefore, its length is given by the number of base pairs
(bp).
-1 kb = 1000 bases or bp; 1 Mb = 1 million bases or
bp. Oligonucleotides refer to short nucleic acid chains (<
50 bases or bp) and polynucleotides have longer
chains.
In cells, a free nucleotide may contain one, two or three phosphate groups. The energy
carrier ATP (adenosine triphosphate) has three phosphate groups; ADP (adenosine
diphosphate) has two; AMP (adenosine monophosphate) has one. Their structures are
shown in the above figure.-(a) A computer model of AMP. (b) Chemical structures of
Adenosine, ADPand ATP. They differ in the number of phosphategroups.
If all phosphate groups are removed, a nucleotide becomes a nucleoside such as
adenosine. The following table lists various nucleosides and nucleotides.
Table . Cellular nucleosides and nucleotides .
• NMP = nucleoside monophosphate
NDP = nucleoside diphosphate
NTP = nucleoside triphosphate
dNMP = deoxynucleoside monophosphate
dNDP = deoxynucleoside diphosphate
dNTP = deoxynucleoside triphosphate
• (nucleoside = ribonucleoside; deoxynucleoside =
deoxyribonucleoside
dGTP
deoxyguanosine triphosphate
dCTP
deoxycytidine triphosphate
dTTP
deoxythymidintriphosphate Thymine
O
CH3
All Pyrimidines and purines can exist in alternative isomeric forms called
tautomers. They can exist in keto (lactam) or enol (lactim)
FIG. Tautomeric forms of Uracil. The lactam form predominates
at pH 7.0; the other forms become more prominent as pH decreases.
The other free Pyrimidines and the free purines also have Tautomeric
forms, but they are more rarely encountered
• Adenine and cytosine,
which contain amino groups,
Can undergo an enamine <->
imine tautomerization
• Guanine and thymine (and
uracil), which contain keto
groups, can undergo a keto
Or enol tautomerization.
Functions of Nucleotide:
They are-
1) Building blocks of Nucleic acids.
2) Carriers of high energy intermediates in the
biosynthesis of carbohydrates, lipid, and proteins.
3) The essential chemical links in response to hormones
and other extracellular stimuli.
4) The structural components of several enzyme co-
factors (coenzymes) and metabolic intermediates.
5) Act as a secondary messengers in hormonal function
of cAMP, cGMP etc.