Clinical implications of genetic and acquired defects in catecholamine synthesis and metabolism.
All major enzymes involved in catecholamine synthesis and metabolism have been cloned. In addition to some genetic defects of these enzymes responsible for well-defined clinical syndromes, several enzymatic abnormalities may be due to environmental (e.g. pharmacological and nutritional) or biological (e.g. aging) factors, which may modify genome expression. The enzymes involved in catecholamine metabolism either lead to metabolites which cannot be reconverted to the parent catecholamine (such as products of monoamine oxidation and catechol-O-methylation), or metabolites, which can be reconverted to the free catecholamine from which they are generated (such as products of sulfoconjugation). Reversible sulfoconjugation is partly regulated by the recently cloned enzyme, sulfatase. The importance of this reversible step is that it reconverts inactive into biologically active catecholamines. The balance of the sulfoconjugation-deconjugation interplay may have physiological implications; in addition to catecholamine release, it may determine the availability of free catecholamines during diurnal rhythms and stress or modify their renal excretion. Circumstantial evidence, including a close homology within the aryl sulfatases and steroid sulfatase gene, the first implicated in catecholamine metabolism, the second in steroid metabolism, suggests a genetic defect of sulfatases in essential hypertension. A similar, but secondary, sulfatase defect may affect catecholamine metabolism and action in chronic renal failure.
Kuchel
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Clinical Research Institute of Montreal, Hôtel-Dieu de Montréal Hospital, Quebec.
D000818:Animals; D015239:Arylsulfotransferase / Q000235:genetics; D002395:Catecholamines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D009154:Mutation
D002395:Catecholamines; D015239:Arylsulfotransferase