FCH 532 Lecture 28. Chapter 28: Nucleotide metabolism Quiz on Monday essential amino acids Wed. April 11-Exam 3 ACS exam is on Monday 5/30 Final is scheduled for May 4, 12:45-2:45 PM, in 111 Marshall.
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Chapter 28: Nucleotide metabolism
Quiz on Monday essential amino acids
Wed. April 11-Exam 3
ACS exam is on Monday 5/30
Final is scheduled for May 4, 12:45-2:45 PM, in 111 Marshall
De novo biosynthesis of purines: low molecular weight precursors of the purine ring atoms
N-(5’-phosphoribosyl) anthranilate isomerase
Indole-3-glycerol phosphate synthase
Tryptohan synthase, subunit
Phosphoribosylformimino-5-aminoimidazole carboxamide ribonucleotide isomerase
Imidazole glycerol phosphate synthase
Imidazole glycerol phosphate dehydratase
L-histidinol phosphate aminotransferase
Histidinol phosphate phosphatase
AMP + ATP
Guanine specific kinase
GDP + ADP
GMP + ATP
ADP + GTP
ATP + GDP
Feedback inhibition is indicated by red arrows
Feedforward activation by green arrows.
Adenine + PRPP AMP + PPi
Hypoxanthine + PRPP IMP + PPi
Guanine + PRPP GMP + PPi
Decarboxylation to form UMP involves OMP decarboxylase (ODCase) to form UMP.
Enhances kcat/KM of decarboxylation by 2 X 1023
UMP + ATP UDP + ADP
UDP + ATP UTP + ADP
CTP is formed by amination of UTP by CTP synthetase
In animals, amino group from Gln
In bacteria, amino group from ammonia
One enzyme, ribonucleotide reductase,
reduces all four ribonucleotides to their
A free radical mechanism is involved
in the ribonucleotide reductase
There are three classes of ribonucleotide
reductase enzymes in nature:
Class I: tyrosine radical, uses NDP
Class II: adenosylcobalamin. uses NTPs
(cyanobacteria, some bacteria,
Class III: SAM and Fe-S to generate
radical, uses NTPs.
(anaerobes and fac. anaerobes).
Free radical abstracts H from C3’
Acid-catalyzed cleavage of the C2’-OH bond
Radical mediates stabilizationof the C2’ cation (unshared electron pair)
Radical-cation intermediate is reduced by redox-active sulhydryl pair-deoxynucleotide radical
3’ radical reabstracts the H atom from the protein to restore the enzyme to the radical state.