B6.038 Metabolism of Purine and Pyrimidine Nucleotides Flashcards
purines
adenine
guanine
pyrimidines
thymine (DNA)
cytosine
uracil (RNA)
starting substrate for de novo purine synthesis
ribose 5-P
manifestations of gout in clinic
acute gouty arthritis
nephropathy
what causes symptoms of gout?
crystal deposition in joints and/or kidneys
urate crystal formation in urine
at low pH: uric acid predominates in urine and uric acid crystals precipitate (common)
at high pH: urate predominates and Na+ urate crystals precipitate (rare)
urate crystal formation in joints
urate predominates and Na+ urate crystals precipitate in synovial fluid and auricles
who is most likely to develop gout?
adult men
95% are under-excreters
diseases w associations w gout
hypertriglyceridemia
hypertension
metabolic syndrome
all related to obesity
factors that lead to chronic urate underexcretion
decreased glomerular filtration in patients with renal failure
inhibition of excretion by organic acids (ketoacidosis, aspirin, excessive alcohol)
chronic dehydration
anything that can decrease amt of urine excreted in general
diagnosis of gout
aspirating fluid from affected joint and finding negatively birefringent crystals under polarizing microscope
benefits of urate
normally in body @ 7-10% concentration
antioxidant properties
when this conc increases in when symptoms emerge
hyperuricemia
too much urate in blood
due to:
-urate overproduction
-under excretion
chronic hyperuricemia
gout
- acute arthritis
- kidney stones
where is ribose-5-p for purine synthesis derived from
pentose phosphate pathway
from glucose-6-p
general overview of de novo synthesis of ATP and GTP
ribose-5-P > PRPP > IMP > AMP or GMP
enzyme which converts ribose-5-p to PRPP
PRPP synthase
- inhibited by ADP
- activated by phosphate
enzyme which converts PRPP to IMP
glutamine-PRPP amidotransferase
- non-reversible
- inhibited by AMP and GMP (feedback)
- activated by PRPP
molecules needed for conversion of PRPP to IMP
folate molecules (N10-formyl-THF)
mycophenolic acid in purine synthesis
inhibits conversion of IMP to GMP
acts as an immunosuppressant
reduces synthesis of DNA/RNA in lymphocytes (primary cells that utilize de novo purine synthesis)
degradation of GMP
GMP > guanine > xanthine (taken up by liver) > urate
degradation of AMP
AMP > hypoxanthine (taken up by liver) > urate