Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purines and pyrimidines, regarded for a long time only as building blocks for nucleic acid synthesis and intermediates in the transfer of metabolic energy, gained increasing attention since genetically determined aberrations in their metabolism were associated clinically with various degrees of mental retardation and/or unexpected and often devastating neurological dysfunction. In most instances the molecular mechanisms underlying neurological symptoms remain undefined. This suggests that nucleotides and nucleosides play fundamental but still unknown roles in the development and function of several organs, in particular central nervous system. Alterations of purine and pyrimidine metabolism affecting brain function are spread along both synthesis (PRPS, ADSL, ATIC, HPRT, UMPS, dGK, TK), and breakdown pathways (5NT, ADA, PNP, GCH, DPD, DHPA, TP, UP), sometimes also involving pyridine metabolism. Explanations for the pathogenesis of disorders may include both cellular and mitochondrial damage: e.g. deficiency of the purine salvage enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase are associated to the most severe pathologies, the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to impairment of mitochondrial functions. This review gathers the presently known inborn errors of purine and pyrimidine metabolism that manifest neurological syndromes, reporting and commenting on the available hypothesis on the possible link between specific enzymatic alterations and brain damage. Such connection is often not obvious, and though investigated for many years, the molecular basis of most dysfunctions of central nervous system associated to purine and pyrimidine metabolism disorders are still unexplained.
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PMID:Neurological disorders of purine and pyrimidine metabolism. 2140 1

Purines and pyrimidines, regarded for a long time merely as building blocks for nucleic acid synthesis and intermediates in the transfer of metabolic energy, have attracted increasing attention after genetically determined aberrations in their metabolism were linked to a range of symptoms from hyperuricemia and immunodeficiency to neurological disorders. The pathogenesis of such disorders involves cell or mitochondrial damage, but the molecular mechanisms underlying symptoms is often unclear. H. Anne Simmonds made major contributions to the metabolic, clinical, and molecular aspects of these disorders and the Purine Research Laboratory, which she established in London, became the world center for clinical and experimental studies in the field. We owe her gratitude not only for this direct contribution but also for her enthusiasm for purine and pyrimidine research that she transmitted to generations of scientists. Our research in this field stemmed from expertise in pyridine metabolism and its connection with purines, and from clinical involvement with biochemical diagnosis of enzyme deficiencies. We joined H. Anne Simmonds in studying the biochemical basis of altered NAD content in erythrocytes of PNP- and HPRT-deficient patients, discovering some alterations in NAD synthesis and breakdown.
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PMID:Inborn errors of purine and pyrimidine metabolism: how much we owe to H. Anne Simmonds. 2213 80


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