title: Molecular biology of metabolic disease: defects in the regulation of enzymic activity.
abstract: The Jacob-Monod model for the regulation of enzymic activity has been used in the analysis of some types of metabolic disease. Three lesions have been considered: (1) loss of allosteric inhibition of phosphofructokinase by citrate in the condition of lipomatosis; (2) failure of covalent modification of triglyceride lipase from inactive to active forms in the condition of triglyceride storage disease, and (3) failure of repression of HMG-CoA reductase by a mutant low-density liprotein in a new variant-of familial hypercholesterolaemia. Defects in enzymic regulation are contrasted with catalytic defects (the inborn errors); the major difference being an accumulation of a normal metabolic end-product of an unregulated pathway, rather than accumulation of an unusual intermediary metabolite as in the inborn errors.
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D000494:Allosteric Regulation; D002384:Catalysis; D002951:Citrates / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006937:Hypercholesterolemia / Q000201:enzymology / Q000235:genetics; D008049:Lipase / Q000378:metabolism; D008068:Lipomatosis / Q000201:enzymology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008659:Metabolic Diseases / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002951:Citrates; D008077:Lipoproteins, LDL; D014280:Triglycerides; D006903:Hydroxymethylglutaryl CoA Reductases; D010732:Phosphofructokinase-1; D008049:Lipase