Metabolism of nucleotides Flashcards
only ___% nucleosides absorbed is reutilized for nucleic acid synth, ___% of these used by rapidly regenerating ____
5; 25; enterocytes
how are ribo and deoxyribo different?
2’ OH (ribo) or H (deoxy)
functions of nucleotides?
precursors for DNA and RNA, ATP, adenine nucleotides for 3 major coenzymes (FAD, NAD, CoA), activated intermediates (UDP=gluc), regulators (cAMP)
2 types of pathways?
de novo, salvage
precursors for de novo?
Asp, CO2, Gly, Gln, formate, R5P
what is PRPP?
phosphoribosylpyrophosphate
inosate has base ___, ___ as nucleotide
hypoxanthine; inosine
what is IMP?
first purine made in de novo, Inosine monophosphate
inhibitors of purine nucleotide biosynth?
purine-containing nucleotides
this condition is characterized by high blood lvls of uric acid due to overproduction or underexcretion of uric acid
gout
symptoms of gout?
pain/inflammation of joints (uric acid crystal deposits)
treatment of gout?
suicide inhibitors (allopurinol), excretion stimulants, diet/alcohol restriction
beer is rich in ___
purines
what is a suicide inhibitor?
bind permanently to active site (no substrate turnover)–>enzyme out of commission
condition due to deficiency in HGPRT activity due to gene mutation (X linked)
Lesch Nyhan syndrome
why is de novo synth ^ by Lesch Nyhan?
PRPP ^ –> IMP/GMP drop –> more substrate for Gln-PRPP amidotransferase, less inhibition by end products –>^ de novo
symptoms of Lesch-Nyhan?
neurological effects (hostility, retardation, self-mutilation, motor dysfunction), gouty arthritis
strategy for de novo pyrimidine synth?
1) synth carbamoyl P 2) build pyrimidine ring (orotate) 3) link ring to R5P
what is rate limiting step of pyrimidine synth?
synth of carbamoyl phosphate
how do CPS1 and CPS2 differ?
1 is in urea synth, 2 is in pyrimidines; 1 is in mito matrix, 2 is in cyto; 1 N donor is NH4, 2 N donor is Gln; 1 reg. effectors are N-acetylGlu and arginine, 2 reg effectors are products (inhibitors)
enzyme for asp –> N-carbamoylaspartate
aspartate trans-carbamoylase
Orotidylate–>?–>?–>?
UMP; UTP; CTP
interconversion of nucleoside mono–>di/tri by this enzyme:
nucleoside monophosphate (specific for base)/diphosphate (nonspecific) kinase
___ and ___ can become dTMP
CDP; UDP
methylation of dUMP by:
THF
this antiviral med is used to treat herpes
acyclovir
how does acyclovir work?
herpes virus have thymidine kinase which has broad specificity; their TK and not human enzyme will phosphorylate acylovir–>no 3’OH after incorporation so it terminates viral DNA synth
medication that is component of HIV cocktail
Zidovudine
mech of action for zidovudine
act as thymidine analog, get incorporated into DNA and prevent further phosphodiester bond formation
common used anti-cancer drug that inhibits thymidylate synth (suicide inhibitor)
5-fluorouracil
example of inhibitor of dihydrofolate reductase (competitive inhbitor)
methotrexate
methotrexate used to treat _____
autoimmune disorders (arthritis, eczema)
