Document Detail

Mechanism of excessive purine biosynthesis in hypoxanthine-guanine phosphoribosyltransferase deficiency.
MedLine Citation:
PMID:  5441549     Owner:  NLM     Status:  MEDLINE    
Certain gouty subjects with excessive de novo purine synthesis are deficient in hypoxanthineguanine phosphoribosyltransferase (HG-PRTase [EC]). The mechanism of accelerated uric acid formation in these patients was explored by measuring the incorporation of glycine-(14)C into various urinary purine bases of normal and enzyme-deficient subjects during treatment with the xanthine oxidase inhibitor, allopurinol. In the presence of normal HG-PRTase activity, allopurinol reduced purine biosynthesis as demonstrated by diminished excretion of total urinary purine or by reduction of glycine-(14)C incorporation into hypoxanthine, xanthine, and uric acid to less than one-half of control values. A boy with the Lesch-Nyhan syndrome was resistant to this effect of allopurinol while a patient with 12.5% of normal enzyme activity had an equivocal response. Three patients with normal HG-PRTase activity had a mean molar ratio of hypoxanthine to xanthine in the urine of 0.28, whereas two subjects who were deficient in HG-PRTase had reversal of this ratio (1.01 and 1.04). The patterns of (14)C-labeling observed in HG-PRTase deficiency reflected the role of hypoxanthine as precursor of xanthine. The data indicate that excessive uric acid in HG-PRTase deficiency is derived from hypoxanthine which is insufficiently reutilized and, as a consequence thereof, catabolized inordinately to uric acid. The data provide evidence for cyclic interconversion of adenine and hypoxanthine derivatives. Cleavage of inosinic acid to hypoxanthine via inosine does not contribute significantly to the formation of uric acid in either normal man or in patients with HG-PRTase deficiency.HG-PRTase was not completely absent in red blood cells from a boy with the Lesch-Nyhan syndrome; with hypoxanthine as substrate, the activity in erythrocyte hemolysates was 0.64% of normal values.
L B Sorensen
Related Documents :
2000819 - Milk- and soy-protein ingestion: acute effect on serum uric acid concentration.
15152659 - Levoglucosan in pm2.5 at the fresno supersite.
3665439 - Seasonal variation in diagnostic enzymes and biochemical constituents of captive northe...
11762669 - Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis.
12585489 - Solution to the problem of interferences in electrochemical sensors using the fill-and-...
16689679 - Characterization of a uricase from bacillus fastidious a.t.c.c. 26904 and its applicati...
22489949 - Identification of a novel hla-a*23 variant allele, a*23:50.
21086469 - Extremely low frequency magnetic field effects on metabolite of aspergillus niger.
1636419 - Effect of exogenous arachidonic acid metabolites applied on round window membrane on he...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  49     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1970 May 
Date Detail:
Created Date:  1970-06-15     Completed Date:  1970-06-15     Revised Date:  2010-09-13    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  968-78     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Allopurinol / administration & dosage
Athetosis / metabolism
Carbon Isotopes
Chorea / metabolism
Compulsive Behavior
Deficiency Diseases / metabolism*
Glycine / metabolism
Gout / metabolism
Guanine / metabolism
Hypoxanthines / metabolism
Inositol / metabolism
Mental Retardation / metabolism
Metabolism, Inborn Errors / genetics
Nucleosides / metabolism
Purines / biosynthesis*,  metabolism
Self Mutilation / metabolism
Transferases / metabolism*
Uric Acid / biosynthesis,  blood
Reg. No./Substance:
0/Carbon Isotopes; 0/Hypoxanthines; 0/Nucleosides; 0/Purines; 315-30-0/Allopurinol; 56-40-6/Glycine; 69-93-2/Uric Acid; 6917-35-7/Inositol; 73-40-5/Guanine; EC 2.-/Transferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Metabolism of beta-sitosterol in man.
Next Document:  On the influence of extracellular fluid volume expansion and of uremia on bicarbonate reabsorption i...