1. Components of Nucleic Acids
Lecture # 2
Dr. Shumaila Asim

2. Nucleotides contain;
Base + sugar + phosphoryl group

3. Base + sugar (ribose or deoxyribose)
Nucleosides contain;
Base + sugar (ribose or deoxyribose)
Sugar, D-ribose or 2’-deoxy D-ribose, is linked to base via a covalent β-N-glycosidic bond to N-9 of a purine or to N-1 of a pyrimidine
Nucleotides are termed ribonucleotides or deoxyribonucleotides based on whether the sugar is ribose or 2’-deoxyribose

4. Functions of nucleotides
*Nucleic acid biosynthesis
*Energy production and transduction
*Protein biosynthesis
*Regulatory cascades
*İntra- and intercellular signal transduction
*Biosynthesis some biomolecules

5. Some properties of nucleotides
Mononucleotides have a negative charge at physiological pH
Nucleotides absorb UV light
Many coenzymes are nucleotide derivatives
Synthetic nucleotide analogs are used in chemotherapy
Nucleoside triphosphates have high group transfer potential
Some nucleotides are involved in signal transduction

6. 1-Mononucleotides have a negative charge at physiological pH.
The pKs of the primary and secondary phosphoryl groups are about 1.0 and 6.2, respectively
Nucleosides and or free purine or pyrimidine bases are uncharged at physiological pH
2-Nucleotides absorb UV light. The conjugated double bonds of the heterocyclic bases of purines and pyrimidines ensure that nucleosides, nucleotides and polynucleotides absorb UV

7. 3- Many coenzymes are nucleotide derivatives
AMP is present in many coenzymes

9. 4-Nucleoside triphosphates have high group transfer potential because of acid anhydride bonds
High group transfer potential of nucleoside triphosphates allows them to participate as group transfer reagents in various reactions such as protein synthesis or nucleic acid synthesis.

10. 5-Some nucleotides are involved in signal transduction
cAMP and cGMP

11. cAMP (adenosine 3’,5’-monophosphate)
The cyclic phosphodiester cAMP is formed from ATP by the reaction catalyzed by adenylyl cyclase

12. cAMP is a second messenger in signal transduction
Adenylyl cyclase activity is regulated by complex interactions, many of which involve hormon receptors
As a second messenger, cAMP participates numerous regulatory functions by activating cAMP dependent protein kinases
cAMP is broken down by cAMP phosphodiesterase

13. cGMP (guanosine 3’,5’-monophosphate)
cGMP is a second messenger in signal transduction that can act antagonistically to cAMP
cGMP is formed from GMP by guanylyl cyclase
Both adenylyl and guanylyl cyclases are regulated by effectors that include hormones
A phosphodiesterase hydrolyzes cGMP to GMP

14. An increase in the level of the cGMP as response to the nitric oxide serves as the main second messenger during events that characterize the relaxation of smooth muscle

15. 6-Other functions of free nucleotides
ADENOSINE DERIVATIVE NUCLEOTIDES
Adenosine 3’-phosphate 5’-phosphosulfate (active sulfate)
This is the sulfate donor for the formation of the sulfated proteoglycans or urinary metabolites of drugs excreted as sulfate conjugates

16. S-adenosylmethionine (SAM)
This is a form of active methionine
SAM serves as a methyl group donor for methylation reactions
SAM forms propylamine which is required in polyamine synthesis

17. GUANOSINE DERIVATIVE NUCLEOTIDES
Guanosine nucleotides participate in the conversion of succinyl-CoA to succinate, a reaction that is coupled to the substrate level phosphorylation of GDP to GTP
GTP is required for
* activation of adenylyl cyclase (as a allosteric regulator)
*protein synthesis (as a energy source)

18. HYPOXANTHINE DERIVATIVE NUCLEOTIDES
Hypoxanthine ribonucleotide is inosine monophosphate (IMP)
It is precursor for purine nucleotides
IMP is formed by deamination of AMP and amination of IMP re-forms AMP
Nucleotide inosine (hypoxanthine + ribose) is an intermediate in the purine salvage cycle

19. URACYL DERIVATIVE NUCLEOTIDES
UDP-sugar derivatives participate in sugar epimerization
UDP-glucose is the glucosyl donor for biosynthesis of glycogen and glucosyldisaccharides
Other UDP-sugars act as sugar donors for biosynthesis of oligosaccharides of glycoproteins and proteoglycans
UDP-glucuronic acid is the glucuronyl group donor for conjugation reactions

20. CYTOSINE DERIVATIVE NUCLEOTIDES
CTP is required for the biosynthesis of some phosphoglycerides
CTP is required for the biosynthesis of sphingomyelin and other substituted sphingosines

21. Polynucleotides
Mononucleotides are covalently linked through phosphate-group ‘bridges’
Specifically, the 5’-OH group of one nucleotide unit is joined to the 3’-OH group of the next nucleotide by a phosphodiester linkage resulting to release of one molecule water
This results in a dinucleotide
The term oligonucleotide is used for polymers containing 50 or fewer nucleotides