Chapter 25 Flashcards
? is an inhibitor of dihydrofolate reductase and causes amplification of ? genes
DHFR
Two nucleotide synthesis pathways
salvage pathway and de novo pathway
salvage pathway
activated ribose (PRPP) + base
de novo synthesis begins with formation of ? from CPS-II
carbamoyl-P
CPS three catalytic sites
glutamine hydrolysis, carbamic acid phosphorylation, bicarbonate phosphorylation
de novo synthesis of pyrimidines pathway
carbamoyl-p + aspartate»_space; carbamoylaspartate»_space; dihydroorotate»_space; orotate»_space; orotate + PRPP»_space; orotidylate»_space; uridylate
purpose of glutamine hydrolysis site of CPS
make NH3
catalytic power of OMP decarboxylase
accelerates reaction by factor of 10^7
charging of nucleoside monophospahate to NDP
requires specific nucleoside monophosphate kinase
charging of NDP to NTP
requires nonspecific nucleoside diphosphate kinase
Enzymes in de novo synthesis of pyrimidines
ATCase»_space; dihydroorotase»_space; dihydroorotate dehydrogenase»_space;orotate phosphoribosyltransferase»_space; OMP decarboxylase
PRPP synthetase is inhibited by ?
AMP, GMP , IMP
synthesis of CTP from UTP
Gln + water»_space; NH3»_space; NH3 + UTP +ATP»_space; CTP
bicarbonate phosphorylation site is an example of this domain
grasp
grasp domain
holds for nucleophilic attack at phosphoryl group. formation of C-N bonds w/ acyl phosphate intermediates
? can be salvaged by a pyrimidine phosphoribosyl transferase
uracil
de novo purine synthesis
assembled already attached to ribose. made from IMP.
pathway from IMP to AMP
IMP + GTP»_space; adenylosuccinate»_space; AMP + fumarate
pathway from IMP to GMP
IMP + NAD+»_space; xanthylate»_space; xanthylate + ATP + NH3»_space;guanylate
enzymes in AMP synthesis
adenylosuccinate synthase, adenylosuccinate lyase
enzymes in GMP synthesis
IMP dehydrogenase»_space; GMP synthase
adenylosuccinate synthase is inhinited by ?
AMP
IMP dehydrogenase is inhibited by ?
GMP
? analogs inhibit many amidotransferase reactions
glutamine
PRPP is a ? activator of purine synthesis
feed forward
ribonucleotide reductase reaction
ribonucleotides»_space; deoxyribonucleotides
ribonucleotide reducatse must be reduced by ? to reactivate
thioredoxin
ribonucleotide reducatase regulation
Activity site: activated by ATP, inhibited by dATP. Specificity site: cross regulation between purines and pyrimidines
cross regulation between purines and pyrimidines
purines enhance production of deoxypyrimidines. Pyrimidines enhance production of deoxypurines
dCMP deaminase reaction
dCMP»_space; dUMP
thymidylate synthase reaction
dUMP + N5,N10-methyleneTHF»_space; TMP
inhibition of dTMP is commonly used in ?
chemotherapy
? is a suicide inhibitor of thymidylate synthase
FluoroUMP
inhibitors of human DHF reductase
folate analogs methotrexate
in purine catabolism, ? recycles hypoxanthine and guanine
hypoxanthine guanine phosphoribosyltransferase
in purine catabolism, ? recycles adenine
adenine phosphoribosyltransferase
loss of adenosine deaminase results in ?
SCID, severe combined immunodeficiency
high levels of dATP act to tshut off ?
ribonucleotide reductase
uric acid is close to solubility limit. excess uric acid can precipitate and cause ?
gout
? inhibits xanthine oxidase
allopurinol
Lesch-Nyhan syndrome
loss HGPRT results in high levels of PRPP. Leads to high levels of purines and uric acid
