Components of Nucleic Acids Lecture # 2 Dr. Shumaila Asim

Nucleotides contain; Base + sugar + phosphoryl group

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

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

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

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

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

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.

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

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

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

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

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

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

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

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)

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

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

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

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