Nucleotide Chemistry PDF

Nucleotide chemistry Prof. Dr/ Yasser Elghobashy Medical Biochemistry and Molecular Biology  ILOs 1. Describe the biochemical functions of nucleotides 2. Illustrate purines and pyrimidine bases and their nucleotides. 3. Define syn and anti- conformers. 4. Id...

Nucleotide chemistry Prof. Dr/ Yasser Elghobashy Medical Biochemistry and Molecular Biology  ILOs 1. Describe the biochemical functions of nucleotides 2. Illustrate purines and pyrimidine bases and their nucleotides. 3. Define syn and anti- conformers. 4. Identify structure of DNA  Nucleotide chemistry Purine and pyrimidine bases and their major derivatives, the nucleosides and nucleotides are the building units of nucleic acids. There are 2 main types of nucleic acids:- 1- Deoxyribonucleic acid (DNA) 2- Ribonucleic acid (RNA) The building unit of nucleic acid is the nucleotide , it consists of ; 1- Nitrogenous base (purine or pyrimidine base) 2- Pentose sugar (ribose or deoxyribose) 3- Phosphate group.  Nucleic acid (polynucleotide) Nucleotide Nucleoside Phosphate Nitrogenous base Pentose sugar (purine or pyrimidine) (ribose or deoxyribose)  Nitrogenous bases (purine and pyrimidine bases) They are heterocyclic ring compounds (contain carbon & nitrogen). There are 2 classes according to their abundance in cells. 1) Major bases :- present in large amount ,they include : – Purines: - adenine, guanine present both in DNA and RNA. – Pyrimidines :- Cytosine: - present both in DNA and RNA. Thymine: - present in DNA only. Uracil: - present in RNA only Purine bases Adenine (6 aminopurine) Guanine (2 amino-6-oxypurine) Pyrimidine bases Cytosine (C) Thyamine (T) Uracil (U) (2-oxy-4-amino- pyrimidine) (2,4-dioxy-5-methyl- pyrimidine) (2,4-dioxy- pyrimidine) 2) Minor bases: - Present in trace amounts and always methylated e.g. 5- methyl cytosine and N7-methylguanine. – Minor bases serve important functions; 1. Oligonucleotide recognition. 2. Regulating the half-life of RNA's. 3. Protecting host DNA from digestion by DNAses. There are bases present in free State inside cells e.g. xanthine, hypoxanthine and uric acid. Methylated xanthine as: Caffeine (1, 3, 7 trimethyl xanthine) in coffee, theophylline (1, 3 dimethyl xanthine) in tea and theobromine (3, 7 dimethyl xanthine) in coca.  Nucleosides It consists of base and sugar (ribose or deoxyribose). Sugars bind bases via a covalent, β-N-glycosidic bond that link C1 of sugar with N-9 of a purine or N-1 of a pyrimidine. Numbering of the sugar atoms employs a prime (e.g 3` or 5`) to distinguish sugar atoms from those of the base.  Nucleotides The nucleotide consists of; Base, sugar and phosphate. Phosphate is attached to C-5 of the sugar.  Tautomerism Purines and pyrimidines are present in 2 isoforms :- – Keto (or lactam) or enol (lactim) form. – Amino (-NH2) or imino (=NH) form. Tautomerism: - Is the change from one form to the other. At physiological PH: - The keto and amino forms are common.  Syn and anti-conformers The nucleotides are present at stable non- interconvertable syn and anti conforms. The β-N-glycosidic bond is a very firm bond so; there is no freedom of rotation about this bond. Interconversion from one form to another occurs only by rupture and reformation of the glycosidic bond. The anti-conformer predominates.  Bases, nucleosides and nucleotides nomenclature Base Nucleoside Nucleotide Adenine (A) Adenosine Adenosine monophosphate (AMP) Deoxyadenosine Deoxyadenosine monophosphate (dAMP) Guanine (G) Guanosine Guanosine monophosphate (GMP) Deoxyguanosine Deoxyguanosine monophosphate (dGMP) Xanthine (X) Xanthosine Xanthosine monophosphate (XMP) Hypoxanthine (I) Inosine Inosine monophosphate (IMP) Cytosine (C) Cytidine Cytidine monophosphate (CMP) Deoxycytidine monophosphate (dCMP) Uracil (U) Uridine Uridine monophosphate (UMP) Thymine (T) Thymidine Thymidine monophosphate (TMP)  Functions of nucleotides A. Both Purine and pyrimidine nucleotides enter in structure of nucleic acids; DNA and RNA. B. Purines nucleotides enter in the structure of :- 1. High energy stores ATP and GTP. 2. Intracellular signals: - cAMP and cGMP act as 2nd messenger for many hormones. 3. Enter in the structure of many coenzymes such as NAD, NADP, FAD and FMN which act as hydrogen carrier. COASH, which act as acid carrier.  4. The active methyl donor (S- adenosyl methionine, SAM). 5. The active sulfate donor (3'phosphoadenosine-5'- phosphosulfate, PAPS). 6. They serve regulatory functions e.g. ADP levels regulate the rate of oxidative phosphorylation in mitochondria. C. Pyrimidine nucleotides:- 1. Enter in the structure of high energy intermediates: Uridine diphosphate glucose (UDP-glucose) used in glycogenesis and uronic acid pathway. 2. High energy stores CTP and UTP. ATP  Bases, nucleosides and nucleotides nomenclature Base Nucleoside Nucleotide Adenine (A) Adenosine Adenosine monophosphate (AMP) Deoxyadenosine Deoxyadenosine monophosphate (dAMP) Guanine (G) Guanosine Guanosine monophosphate (GMP) Deoxyguanosine Deoxyguanosine monophosphate (dGMP) Xanthine (X) Xanthosine Xanthosine monophosphate (XMP) Hypoxanthine (I) Inosine Inosine monophosphate (IMP) Cytosine (C) Cytidine Cytidine monophosphate (CMP) Deoxycytidine monophosphate (dCMP) Uracil (U) Uridine Uridine monophosphate (UMP) Thymine (T) Thymidine Thymidine monophosphate (TMP)