Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A now 45-year-old man with marked chronic tophous gout and recurrent nephrolithiasis has been followed for 12 years. First gouty symptoms appeared at age 18. Uric-acid reducing treatment freed the patient of symptoms, and bony and soft-tissue tophi in part regressed. The early onset and high urinary uric-acid excretion indicated increased uric-acid production. Decreased activity of the enzyme hypo-xanthine-guanine-phosphoribosyl transferase was demonstrated to be the cause of the hyperuricaemia, which led to an excessive purine synthesis. An almost complete loss of activity of this enzyme is the basis of the Lesch-Nyhan syndrome. In the described patient all of the neurological and behavioural disorders of the Lesch-Nyhan syndrome were absent. A pheochromocytoma was found to be the cause of malignant hypertension, which had been present for many years.
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PMID:[Juvenile gout with decreased activity of hypoxanthine-guanine-phosphoribosyl transferase and pheochromocytoma: partial persistence of tophi despite uric-acid reducing treatment for 12 years (author's transl)]. 66 12

Lesch-Nyhan syndrome results from a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). It is manifest by behavioral abnormalities, including self-mutilation, and evidence of abnormal 3,4-dihydroxyphenylethylamine (dopamine) metabolism. To assess whether an HPRT deficiency in a dopaminergic cell can adversely affect dopamine metabolism in that cell, dopamine metabolism was examined in HPRT-deficient variants of PC12 pheochromocytoma cells and in cells that had regained HPRT activity by virtue of transformation with a recombinant retrovirus containing the human gene for HPRT. There was no correlation between HPRT activity and endogenous dopamine levels, dopamine uptake, dopamine release, or monoamine oxidase activity. Transformation with the HPRT retrovirus did not adversely affect dopamine metabolism.
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PMID:Dopamine metabolism in hypoxanthine-guanine phosphoribosyltransferase-deficient variants of PC12 cells. 351 67

Purines are a class of small organic molecules that are essential for all cells. They play critical roles in neuronal differentiation and function. Their importance is highlighted by several inherited disorders of purine metabolism, such as Lesch-Nyhan disease, which is caused by a deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Despite the known importance of purines in the nervous system, knowledge regarding their metabolism in neurons is limited. In the current studies, purine pools and their metabolism were examined in rat PC6-3 cells, a PC12 pheochromocytoma subclone that undergoes robust differentiation with nerve growth factor. The results were compared with five new independent PC6-3 subclones with defective purine recycling because of different mutations affecting HGprt enzyme activity. The results demonstrate an increase in most purines and in energy state following neuronal differentiation, as well as specific abnormalities when purine recycling is lost. The loss of HGprt-mediated purine recycling also is associated with significant loss of dopamine and related metabolites in the mutant PC6-3 lines, suggesting an important connection between purine and dopamine pathways. These results provide insights into how purine pools and metabolism change with neuronal differentiation, and how specific enzyme defects may cause neuronal dysfunction. Differentiation of dopaminergic PC6-3 cells is accompanied by increased purine pools and energy state. The lack of a functional purine recycling pathway causes purine limitation in both undifferentiated and differentiated cells, as well as profound loss of dopamine content. The results imply an unknown mechanism by which intracellular purine levels regulate dopamine levels.
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PMID:Purine metabolism during neuronal differentiation: the relevance of purine synthesis and recycling. 2385 90