Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphoribosylpyrophosphate(PRPP) synthetase(PRS) catalyzes the formation of PRPP from ATP and ribose-5-phosphate. PRPP is an important substrate for the synthesis of purine, pyrimidine, and pyridine dinucleotides. Human PRS exists as complex aggregates composed of the 34 kDa catalytic subunits(PRS1 and PRS2) and other 39 kDa component designated PRPP synthetase-associated protein (PAP39). PRS superactivity is an X-chromosome linked disorder, characterized by gout and uric acid overproduction resulting from accelerated synthesis of PRPP and purine nucleotides. Among the nearly 30 affected families identified to date, there are several families in which PRS superactivity with purine nucleotide feedback resistance are associated with neurodevelopmental abnormalities in addition to hyperuricemia and gout. Different nucleotide substitutions in the PRPS1 gene encoding PRS1 have identified in six unrelated affected families with purine nucleotide feedback-resistant PRS superactivity.
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PMID:[PRPP synthetase superactivity]. 897 11

PRPP(phosphoribosyl pyrophosphate) synthetase catalyzes the formation of PRPP from ATP and ribose 5-phosphate. Human PRPP synthetase exists as heterogeneous aggregates composed of the 34kDa catalytic subunits (PRSI and PRSII) and other 39kDa and 41kDa components designated PRPP synthetase-associated protein (PAP39 and PAP41). A syndrome of increased activity of PRPP synthetase, an X-linked dominant-inherited disorder, is one of the models of gout caused by increased production of uric acid. By now, around twenty cases have been reported over the world. Two different molecular mechanisms underlie this syndrome: (1) point mutation in the gene coding the primary structure of PRPP synthetase causes the substitution of an amino acid residue and, consequently, the regulatory defects, those are resistant traits to allosteric nucleotide feedback inhibition; (2) increased transcription of PRPP synthetase mRNA causes overproduction of this enzyme protein. The mechanism producing increased mRNA is, however, not elucidated. The Japanese case has been found to be caused by the second mechanism.
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PMID:[Increased activity of PRPP synthetase]. 1840 17