MET ABLISM: Str uctur e and Metabolism of ucleotide USMA SUM FRIED T AMBUA ARLI ADIT YA PARIKESIT RID UT M
ucleotide Function Building blocks for DA and RA Intracellular source of energy - Adenosine tr iphosphate (AT P) Second messengers - Involved in intracellular signaling (e.g. cyclic adenosine monophosphate [camp]) Intr acellular signaling switches (e.g. G-pr oteins)
Structure of a ucleotide Despite the complex ity and diversity of life the structure of DA is dependent on only 4 differ ent nucleotides Diversity is dependent on the nucleotide sequence All nucleotides are 2 ring structures composed of: 5-carbon sugar : Base Phosphate group -D-ribose (RA) -D-deoxyribose (DA) Purine Pyrimidine A nucleotide WITHUT a phosphate group is a UCLESIDE
Structure of a ucleotide: Sugar A nucleotide is made of 3 components: 5 HCH 2 4 1 A Pentose sugar T his is a 5 carbon sugar T he sugar in DA is deox yribose (lacks a 2 H group) T he sugar in RA is ribose HCH 2 H Ribose 3 2 Deoxyribose H HCH 2 H H H H
Structure of a ucleotide: Bases - Purines H 2 8 7 9 5 4 6 3 1 2 Adenine Guanine H H A G H H 2
ucleotide Structure - 2 Bases - Pyr imidines H 3 C H T Thymine 3 4 5 H 2 1 6 Sytosine H 2 C H
ucleotide Str uctur e: Bases - Pyr imidines T hymine is found LY in DA. In RA, thymine is replaced by uracil Uracil and T hymine are structurally similar H 3 C H T H U H H
Phosphate Gr oups Phosphate groups are what makes a nucleoside a nucleotide Phosphate groups are essential for nucleotide poly mer ization P X Basic structure
Phosphate Gr oups umber of phosphate gr oups deter mines nomenclatur e Monophosphate P CH 2 Diphosphate P P CH 2 T riphosphate P P P CH 2
Base-Sugar-P 4 2- Monophosphate P C 5 3 2 4 1 5 6 Base 4 1 Phosphate 3 2 H Sugar
Sugar Phosphate backbone ucleotide ucleic Acid Structure Poly mer ization
ucleic Acid Structure: Base Pair ing RA [normally] exists as a single stranded poly mer DA exists as a double stranded polymer DA double strand is created by hydrogen bonds between nucleotides ucleotides always bind to complementary nucleotides A T (2 H-bonds) G C (3 H-bonds)
ucleic Acid Structure Base Pair ing hydrogen bonds
Sy nthesis Pathway s For both purines and pyrimidines there are two means of synthesis (often regulate one another) de novo (from bits and parts) salvage (recycle from pre-ex isting nucleotides)
Many Steps Require an Activated Ribose Sugar (PRPP) 5
de novo Synthesis Committed step: T his is the point of no return ccurs early in the biosynthetic pathway ften r egulated by final pr oduct (feedback inhibition) X
Pur ine Biosynthesis (de novo) Feedback inhibitors: AMP, ADP, GMP, GDP, IMP R-5-P PRPP PRA IMP AMP ADP AT P GMP GDP GT P PRA: 5-phosphor ibosy l-1-amine. activation inhibition
Salvage Pathway for Pur ines Hypoxanthine + PRPP Guanine + PRPP IMP + PP i GMP + PP i Hypoxanthineguanosylphosphoribosyl transferase (HGPRTase) Adenine + PRPP AMP + PPi Adeninephosphoribosyl transferase (APRTase)
Regulation of py r imidine nucleotide sy nthesis C 2 + Gln + AT P - Inhibited by UMP Car bamoy l phosphate - -Car bamoy laspar tate Inhibited by CTP UMP
Salvage pathway for pyrimidine nucleotide biosy nthesis PRPP Pyrimidine ribonucleoside PPi Pyrimidine Phosphoribosyl transferase Pyrimidine monophosphate rotate UMP PRPP PPi rotate Phosphoribosyl transferase rotidylate H + C 2 rotidylate decarboxylase
Conclusion ucleotides are composed of 5-carbon sugar, Base, and Phosphate group For both purines and pyrimidines there are two means of synthesis: de novo salvage
Refer ences Fry M. 2011, Essential Biochemistry for Medicine Wiley Garrett R.H. et al. 2012 Biochemistry Brooks Cole Publishing Company Harvey R.A. et al. 2011 Biochemistry Wolters Kluwer Health/L ippincott Williams & Wilkins Laemmerhofer M. et al. 2013 Metabolomics in Practice: Successful Strategies to Generate and Analy ze Metabolic Data Wiley Mathews C.K. et al. 2000 Biochemistry Benjamin Cummings Murray R.K. et al. 2012. Harper s Illustrated Biochemistry. 29 th edition. McGraw Hill Medical. elson D.L and Cox M.S. 2008. Lehninger Principles of th