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MBC - Lecture 52

Purine Metabolism (Mock)

Lecture 52 Purine Metabolism
___ is the parent nucleotide for AMP and GMP. IMP
___ steps/reactions in IMP synthesis. 11
PRPP Synthetase Catalyzes synthesis of 5-phosphoribosyl-1-pryophosphate (PRPP) from ribose 5-phosphate
Glutamine PRPP Amidotransferase Catalyzes synthesis of 5-phosphoribosylamine from PRPP (nitrogen from glutamine)
IMP branches to ___ or ___ by two steps. AMP or GMP
IMP, GMP, and XMP negative feedback at same site on ___. glutamine PRPP amidotransferase
AMP negative feedback at a different site on ___. glutamine PRPP amidotransferase (same enzyme, different site)
GMP and AMP negative feedback at respective: respective IMP branch point
Feedback regulation of glutamine PRPP amidotransferase is the: conversion from inactive to active state
IMP, GMP, and AMP promote the ___ state. inactive
PRPP promotes the ___ state. active (positive feedback)
PRPP pool size ___ purine nucleotide synthesis. regulates
Purine ribonucleotides act as ___ for PRPP synthetase and glutamine PRPP amidotransferase. allosteric regulators
Glucose-6-Phosphatase Deficiency (GSD Type I, Von Gierke’s Dsiease) Increased flux through pentose phosphate pathway and adenine nucleotide pool degradation
Increased flux through pentose phosphate pathway yields: Increased ribose-5-phosphate, PRPP, IMP/GMP/AMP, and uric acid production
Uric acid overproduction causes ___. gout
Adenine Nucleotide Degradation Type 1 GSD and fructose intolerance, F-1-P aldolase/aldolase B deficiency, triggered by decreased Pi
Purine bases and nucleosides can be salvaged to ___ form. mononucleotide
Adenine Phosphoribosyl Transferase Catalyzes phosphoribosylation of adenine forming AMP, using PRPP and releasing PPi
Hypoxanthine-Guanine Phosphoribosyl Transferase (HGPRTase) Catalyzes phosphoribosylation of hypoxanthine or guanine forming IMP or GMP, using PRPP and releasing PPi
AMP Deaminase Catalyzes deamination of adenine nucleotide to IMP, releasing NH4+
Adenosine Deaminase Catalyzes deamination of adenosine to inosine, releasing NH4+
5’-Nucleotidase is due to: IBE increased 5’-nucleoside
5’nucleotidase causes: developmental delay, seizures, ataxia, language deficit, hyperactivity, short attention span, poor social interaction, increased infections, and anemia
5’-nucleotidase is treated with ___ supplement. uridine
Uricase Catalyzes degradation of uric acid to allantoin
Uricase is ___ in humans. absent (would prevent gout if present)
Rasburicase IV can prevent ___. acute uric acid nephropathy
Allopurinol and alloxanthine are ___ that inhibit ___. structural analogs, xanthine oxidase
Enzyme defects that can lead to excessive excretion of urate: PRPP synthetase, HGPRTase, glucose-6-phosphatase
PRPP Synthetase Deficiency “Gout", increased Vmax/inhibition resistance/low Km, purine overproduction and over excretion, X-linked recessive
HGPRTase (Partial Deficiency) “Gout”, purine overproduction and over excretion, X-linked recessive
HGPRTase (Complete Deficiency) “Lesch-Nyhan Syndrome”, purine overproduction and over excretion, self-mutilation
Adenine Phosphoribosyltransferase Deficiency “Renal Lithiasis”, 2,8-dihydroxyadenine renal lithiasis, autosomal recessive
Xanthine Oxidase “Xanthinuria”, xanthine renal lithiasis, hypouricemia, autosomal recessive
Urates are ___ soluble than uric acid. more
Uric acid stones are reduced by ___ of urine. alkalinization
Hypouricemia leads to __. tophi
Tophi Crystallization of sodium urate in soft tissues and joints
Tophi causes an inflammatory reaction, ___. acute gouty arthritis
Adenosine Deaminase Deficiency “Immunodeficiency”, T- and B-cell immunodeficiency (SCIDS), deoxyadenosinuria, autosomal recessive
Purine Nucleoside Phosphorylase Deficiency “Immunodeficiency”, T-cell immunodeficiency, inosinura/deoxinosinuria/guanosinuria/deoxguanosinuria, hypouricemia, autosomal recessive
AMP Deaminase Deficiency “Monoamine Deaminase Deficiency” (MADD), muscle pain/cramping/fatigue, autosomal recessive
Purine analogs block ___. purine nucleotide biosynthesis
6-mercaptopurine inhibits ___. PRPP-amidotransferase
Azathioprine is a ___ analog, metabolized to ___. purine, 6-MP
Created by: emyang