Nucleic Acids Metabolism (Biosynthesis & Degradation) PDF

Biosynthesis of Nucleotides Two ways: – De Novo Pathway: means from scratch through precursor molecules; – nucleotide bases are produced from simpler compounds Purines: base is synthesized in segments, in order, directly onto the ribose structure Pyrimidines: ba...

Biosynthesis of Nucleotides Two ways: – De Novo Pathway: means from scratch through precursor molecules; – nucleotide bases are produced from simpler compounds Purines: base is synthesized in segments, in order, directly onto the ribose structure Pyrimidines: base is synthesized first and then assembled onto the ribose structure – Salvage Pathway: “a process whereby a metabolite is reutilized for biosynthesis of a compound from which the metabolite was derived” Dr AMK 1  De novo purine synthesis Purine ring is synthesized by a series of 12 reactions during which carbon and nitrogen atoms are added to a pre-formed ribose- 5-phosphate that is first converted to PRPP. Note: Ribose-5-phosphate is produced from Hexose MonoPhosphate Pathway. Dr AMK 2 Dr AMK 3 Purine Synthesis-precursors Dr AMK 4 Dr AMK 5 Dr AMK 6 Dr AMK 7 Dr AMK 8 Dr AMK 9 Dr AMK 10 Dr AMK 11 Dr AMK 12 Dr AMK 13 Enzymes catalyzing above reactions form step 1 to step 11 Dr AMK 14 Dr AMK 15  Pyrimidine Synthesis Pyrimidine ring is completely synthesized first and then it is attached to a ribose-5-phosphate donated by PRPP Source of carbons and nitrogens less diverse than purines. 16 Dr AMK  17 Dr AMK Dr AMK 18 Dr AMK 19 Dr AMK 20 Dr AMK 21 De novo purine synthesis AMP ADP ATP Adenosine Adenosine monophosphate diphosphate kinase kinase IMP GMP GDP GTP Guanosine Guanosine monophosphate diphosphate kinase kinase De novo pyrimidine synthesis UMP UDP UTP Uridine monophosphate kinase Uridine diphosphate kinase dUMP dUDP CTP Thymidylate synthase Thymidine Thymidine dTMP dTTP monophosphate kinase diphosphate 22 23 kinase Dr AMK Dr AMK 23 Dr AMK 24 Dr AMK 25 Dr AMK 26  Purine Salvage Pathway Reutilization of adenine, hypoxanthine, and guanine – Two enzymes: Adenine phosphoribosyltransferase Hypoxanthine-guanine phosphoribosyltransferase Guanine/ Hypoxanthine + PRPP GMP + PPi Dr AMK 27 The symptoms of Lesch-Nyhan syndrome include impaired kidney function, acute gouty arthritis, and self-mutilating behaviors such as lip and finger biting and/or head banging. Additional symptoms include involuntary muscle movements, and neurological impairment. Dr AMK 28  29 Dr AMK  30 Dr AMK DNA Replication: DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule Dr AMK 31 Dr AMK 32 Dr AMK 33 5’ 3’ 5’ RNA DNA Polymerase Primer Nucleotide Dr AMK 34 Dr AMK 35 (other than polymerases ) Enzyme Helicase unwinds and separates the 2 DNA strands by breaking the weak hydrogen bonds Single-Strand Binding Proteins attach and keep the 2 DNA strands separated and untwisted Enzyme Topoisomerase attaches to the 2 forks of the bubble to relieve stress on the DNA molecule as it separates Primase is the enzyme that synthesizes the RNA Primer Dr AMK 36 Dr AMK 37 Dr AMK 38  39 Dr AMK Dr AMK 40 Dr AMK 41 The primase activity is associated with Pol α. 42 Dr AMK Dr AMK 43 Dr AMK 44 Dr AMK 45 Transcription RNA is synthesized by the DNA dependent RNA polymerases. Dr AMK 46 Dr AMK 47 Dr AMK 48 Dr AMK 49 Dr AMK 50 Dr AMK 51 1 2 Dr AMK 52 Dr AMK 53 Dr AMK 54 Dr AMK 55 Inhibitors of transcription Dr AMK 56