Nucleotide Metabolism Flashcards
purine and pyrimidines
purines = 2 rings
adenine, guanine
pyrim = 1 ring
cytosine, urasil, thymine
nucleoside + Pi = nucleotide
important precursor for all nucleotides
PRPP
ATP+ribose-5-Pi —-> PRPP+AMP
via PRPP synthetase
pyrimidine-related enzymes to know
CPSII ATCase dihydroorotase dihydroorotase dehydrogenase UMP synthetase nucleoside mono-Pi kinase nucleoside di-Pi kinase CTP synthetase
purine related enzymes to know
purinosome
purine synthesis
branch off from IMP
- AMP
- –uses GTP for nrg
- –replaces carbonyl w/ NH3
- –inhibited by AMP - GMP
- –uses ATP
- –redox w/ H2O to make 2nd carbonyl
- –replaces it w/ NH3
- –inhibited by GMP
deoxyribonucleotide synthesis overview
converting ribose to deoxyribose requires reduction rxn
deoxyribonucleotides are created from their respective NDPs
**pyrimidines take a detour
ribonucleotide reductase
1 enzyme acts on all NDPs and NTPs
NADPH provides e-for redox
regulation
- -active site = catalytic site
- -allosteric sites = specificity site and activity site
salvage
- pyrimidines use phosphorylases and kinases for salvage in 2 steps
- purines use phosphoribosyltransferases to salvage in 1 step
**know thymidine kinase and HPRT
catabolism
nitrogenous bases can be broken down
–uric acid is the final product of purine catabolism
–B-ureidopropionic acid can be converted to alanine + CO2 + NH3 by ureidopropionase
to complete pyrimidine catabolism
what enzymes are deficient for the following genetic medical conditions?
- megaloblastic anemia
- gout
- lesch-nyhan syndrome
- SCID
- UMP synthetase
- HPRT
- HPRT
- adenosine deaminase
CPSII
carbamoyl pi synthetase II
has a channel
starts w/ bicarbonate
ends w/ carbamoyl Pi
ATCase
aspartate transcarbamoylase
has 2 allosteric regulators
- ATP activates
- CTP inhibits
dihydroorotase
closes the ring
–reverse of a hydrolase
carbamoylasparate to dihydroorotate
dihydroorotate dehydrogenase
located in mito
dihydroorotate to orotate
UMP synthetase
multifunctional protein
- removes PPi when orotate added to PRPP
- decarboxylates orotate to form uracil
megaloblastic anemia
occurs when cells fail to divide
B9 or B12 deficiencies
but fails to respond to vit B treatment because of a deficiency in UMP synthetase
NMP kinase
transforming UMP to UTP
UMP+ATP = UDP + ADP
uracil
NDP kinase
transforming XMP = XTP
XDP + YTP = XTP + YDP
also used in transforming UMP to UTP (uracil) but this enzyme has broad specificity
CTP synthetase
CTP or cytosine is the only nucleotide to be synthesized directly as a triphosphate
CTP synthetase has 2 allosteric regulators
1. GTP activates
2. CTP inhibits
(same as ATCase)
purines - rxns 1-3
form the 5 membered ring
- swaps PPi on PRPP for NH3 from Gln
- adds glycine
- adds formyl group to complete ring
purines - rxns 4-10
form the 6 membered ring
- adds NH3 from Gln to start 2nd ring
- closes the 5C ring
- adds CO2 from HCO3 first to Gln then to Gly
- adds Asp to carboxyl
- release fumarate
- 2nd formyl group added to complete the 6C ring
closure forms hypoxanthine
purinosome
purines are made in purinosome
6 enzymes do 10 rxns
—rxns carried out on proteins
2 additional enzymes provide formyl groups
—proximity regulates flow
thymidylate synthase
adds methyl to dUMP to create dTMP
pyrimidine salvage
nucleobases to nucleosides
—nucleoside phosphorylase
nucleoside to nucleoside mono-Pi
—nucleoside kinase
pyrimidine salvage takes 2 steps
- phosphorylase makes nucleoside
- kinases make nucleotides
