Nucleotide Metabolism Notes PDF

d L\,s* TN rff' q u#I\rgxs*TY *r KWKXtILU-f{&T&L DEPARTMENT OF BIOCHEMISTRY (Westville Campus) BIOC 202: BIOENERGETICS AND IttrccRATED METABoLISM NUCLEOTIDE METABOLISM  INTRODUCTION TO NUCL...

d L\,s* TN rff' q u#I\rgxs*TY *r KWKXtILU-f{&T&L DEPARTMENT OF BIOCHEMISTRY (Westville Campus) BIOC 202: BIOENERGETICS AND IttrccRATED METABoLISM NUCLEOTIDE METABOLISM  INTRODUCTION TO NUCLEOTIDE METABOLISM NAMING OF NUCLEOTIDES Nucleotides are made up of three components: Base + Sugar + Phosphate. They are named according to examples given in Table 1. Table 1. Names, and abbreviations of nucleic acid bases, nucleosides, and nucleotides. Base Base Nucleoside Nucleotide' Formula X:H X : riboseo X : ribose phosphateo T'' Adenine Adenosine Adenylic acid Nr'-r\ Ade Ado Adenosine monoPhosPhate (-,A*) A A AMP ,*l x o Guanine Guanyiic acid '--*A--\ tll ) Gua Guanosine Guo Guaaosine monopbosPhate GG GMP urNAN^1 x NH" t' *A tll C]'tosine c)'t Cytidine cvd Cytidylic acid Cytidine mouophosPhate oAx/ C C CMP I x o 't-*A rll Uracil Uridine Urd Uridylic acid Urdine monopbosphate Ura oAN/ U U I.IMP I x o "--*\"', tll Thlmine Thv Deoxythymidine dThd Deoxythymidylic acid Deoxythymidine monoPhosPhate nAN/ T dT dTMP I dx Thepresence ofa 2,deoxyribose unitin place of ribose, as occurs in DNA, isimpliedbythepretxes "deoxy" or a 2..d." For example, the deoxynucleoside oiadenine is deoxyadenosine or dA. However, for tlyndne-containing Tbe presence ofa ribose unit residues, which rarely occurin RNA, tbe prefix is redunda:rt and may be dropped' the prefixes *ribo" or "r." Thus the ribonucleotide of thymiae is ribothrmidhe may be explicitiy implied by or rT. i The position of the phospbate group in a nucleotide may be explicitly specified as in, for example, 3'-AMP and 5'- GMP.  2. FUNCTIONS OF NUCLEOTIDES Nucleotides play key roles in nearly all biochemical processes: a They are activated precursors of DNA and RNA' a Their derivatives are activated intermediates in biosynthetic pathways e.g. UDP-GIucose, CDP-diacylglycerol, S-adenosylmethionine. ATP is the energy currency in biological systems while qIP powers movement of matromolecules and activates signal-coupling proteins. Nucleotides are involved in regulation of metabolic activity: cAMP is a mediator in hormonal action. eovalent modification of proteins. through phosphorylation by ATP alters their activity. The levels of ATP, ADP ind AMp-can regulate flux through metabolic pathways. Nucleotides can also act as coenzymes e.g. NAD*, NADP*, FMN, FAD, CoA. 3. BIOSYNTHESIS OF NUCLEOTIDES Nucleotides are synthesized from simple building blocks (de novo s/nttresis) that initude amino acids, tetrahydrofolate derivatives, NHu*, iOr, with the sugar moiety coming from S-phosphoribosyl-1- pyr5'pf,'osphate, In activat-eO Oonor. They can also be synthesized from r6cybling preformed bases (salvage synfhesrs). Deoxyribonucleotides are formed by reduction of ribonucleotides while dTMP is formed by methylation of dUMP- 4. BIOSYNTHESIS OF PURINES The purine ring structure is built on 5'-phosphoribosyl;o-pyrop.hosphate (pRpp) which-is also a precursor in pyrimidine, histidine and tryptophan Liosynitresis. This allowi for co-regulation of purine and pyrimidine biosynthesis. The source of atoms in the purine ring structure are aspadate amine, formate, bicarbonate, glutamine amide and glycine (Fig 1). The common precursor of AMP and GMP is IMP which is first synthesized from PRPP. HCOt I I *t GlYcine ;/ Aspartate "o,lr** TfY\?-I1^ l- I ac