Nucleotides, structure and function By Dr Rehab Omer

Nucleotides Structure Each nucleotide is composed of: Five-carbon sugar. Phosphate group. Nitrogenous base. Nucleotide subunits of RNA contain a pentose sugar called ribose. Nucleotide subunits of DNA contain the sugar deoxyribose.

Structure of purine and pyrimidine nucleotides nucleotide = phosphate + a nucleoside nucleoside = Nitrogenous base +pentose sugar Nitrogenous bases: aromatic heterocycles purines: pyrimidine + imidazol ring pyrimidines: pyrimidine ring

Structure of bases Purines and pyrimidines are nitrogen-containing heterocycles compounds whose rings contain both carbon and other elements (hetero atoms).

Nitrogenous Bases Structure

The nucleosides Consist of a purine or pyrimidine base linked to a carbohydrate pentose sugar . This pentoses can be D-ribose as (in RNA) or can be 2-Deoxy –D ribose (in DNA ) .

Nucleotides Structure The five carbon atoms in each pentose are assigned numbers 1/ through 5/. Primes are used in the numbering of the ring positions in the sugar to differentiate them from the ring positions of the bases

The nucleosides nucleosides are formed by coupling of carbon 1of D-ribose or deoxyribose and nitrogen 9 of all purine bases through a 1,9 β-N-glycosidic bond . or by coupling of carbon 1of D-ribose or deoxyribose and nitrogen 1 of pyrimidine bases (thymine , cytosine ) through a 1,1-β-N-glycosidic bond.

ribonucleosides deoxyribonucleoside

Nucleotides Structure Phosphate functional group (PO4): Gives the DNA and RNA the property of an acid at physiological PH, hence the name nucleic acid.

ribonucleotide deoxyribonucleotide

Structure of nucleotides pyrimidine OR purine Ribose or 2-deoxyribose N-b-glycosyl bond

Nucleoside +phosphate (mono, di & tri) Type of bond in nucleotide: Nucleotides Nucleoside +phosphate (mono, di & tri) Type of bond in nucleotide: * N-glycosidic bond * ester bond * anhydride bond

Nucleotides Structure

The ATP

The nucleotides functions 1- Building block of nucleic acids. 2-Energy transduction. 3-Signaling, 2nd messengers. 4- Coenzymes components 5- Regulatory “allosteric” effector. 6- Activated precursors in biosynthesis.

The nucleotides and energy The di- and tri-phosphates of nucleotides are linked by acid anhydride bonds, which have a high ∆G0' for hydrolysis .

The adenosine derivatives The adenosine derivative 3'-5'-cyclic adenosine monophosphate, cAMP is a 2nd messenger in hormonal signal transduction cAMP is also involved in the regulation of ion channels by direct interaction with the channel proteins.

Cyclic adenosine monophosphate (cAMP) 3) physiological mediators cAMP, cGMP („second messengers“) Cyclic adenosine monophosphate (cAMP)

2nd messenger

4) components of coenzymes NAD+, NADP+, FAD, CoA

Guanosine derivatives Cyclic GMP (cGMP) is also involved as a second messenger molecule, in many cases, its' role is to antagonize the effects of cAMP. The most important cGMP coupled signal transduction cascade is the photoreception

5) activated intermediates UDP-Glc CDP-choline, ethanolamine, diacylglycerol 6) allosteric effectors regulation of key enzymes of metabolic pathways

Synthetic nucleotides Synthetic nucleotide analogues are used for therapeutic purposes. They inhibit specific enzymatic activities. Interfere with DNA synthesis, preferentially kill rapidly dividing cells, (anti-tumor agents). Immune suppressors

Anti-tumor drugs Disrupt the normal replication process. The commonly used in anti-tumor chemotherapy include: 6-mercaptopurine, 5-fluorouracil, 5-iodo-2'-deoxyuridine 6-thioguanine.

Anti-viral drugs Nucleotide analogs have also been used to target viruses. Azidothymidine (AZT) and dideoxyinosine (ddI) are used to interfere with the replication of HIV

Enzyme and immune inhibitors Purine analogs are used to treat gout. allopurinol, resembles hypoxanthine, thus inhibits xanthine oxidase Also nucleotide analogues are used after organ transplantation to suppress the immune system and reduce rejection.