Biochemistry Flashcards
Explain why purine biosynthesis is inhibited by AMP and by GMP
negative feedback
What is the correlation between hyperuricemia and gout?
gout only occurs in individuals who are hyperuricemia
What are the crystals made of in gout?
monsodium urate
What is considered abnormally high urate levels?
6.8 mg/L of urate
What is uric acid an end product of?
nucleotide degradation from purines (not pyrimidines)
How is uric acid excreted from the body?
urine or feces
What causes hyperuricemia?
excessive production or inadequate elimination of uric acid
Where are dietary purines oxidized?
liver
Where are de-novo biosythesized purines oxidized?
liver
What causes reabsorption of uric acid in the body?
urate1 transporter in kidney
What are dietary purine sources?
1) red meat
2) seafood
3) beer
What is glutamine-phosphoribosylpyrophosphate aminotransferase?
key regulated step in purine biosynthesis; first step which is inhibited by AMP and GMP and stimulated by PRPP
What is PRPP?
Purine biosynthesis starting substrate which is the foundation which purines are built
How is PRPP formed?
ribose-5-phosphate and PRPP synthetase
What stimulates PRPP formation and what inhibits it?
(+) inorganic phosphate
(-) purines
Where does the ribose-5-phosphate come from?
pentose phosphate pathway
What is the initial intermediate formed during purine biosynthesis?
inosine monophosphate (IMP) PRPP --> IMP
How is inosine monophosphate biosynthesized?
oxidized to XMP which is transaminated to GMP
What is one word to describe how drugs are excreted and metabolized from the body?
oxidation
Why is AMP used to make GTP and GMP used to make ATP?
balance each other out where the product in high concentration increases the levels of the product in low concentration
What are the 3 steps in purine degradation?
1) remove phosphates
2) remove ribose
3) oxidize purine base again
Which enzyme is targeted in anti-gout therapies?
xanthine oxidase
What is purine salvage?
saves energy by salvaging purine bases by reattaching them to PRPP using HGPRT which hydrolyzes phosphate group of PRPP
What is Lesch-Nyhan disease?
HPRT is inactivated by x-linked recessive mutations; leads to severe hyperuricemia
What is the effect of fructose on
purine metabolism?
Dietary fructose gets trapped almost completely in the liver after it gete phosphorylated. This leads to huge increase in monophosphates (GMP, AMP) and results in increased purine metabolism –> gout
What is a byproduct of uric acid?
allantoin from urate oxidase; way to expel uric acid from body
