3-hydroxy-3-methylglutaryl-CoA synthase deficiency
ثبت نشده
چکیده
Deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, the rate-limiting enzyme in hepatic ketogenesis, causes potentially life-threatening hypoglycemic hypoketotic coma during fasting periods. In the normal, nonfasting state, patients are completely asymptomatic and show no abnormalities in standard metabolic tests. As a consequence, diagnosing 3-hydroxy-3-methylglutaryl-CoA synthase deficiency has been thought to be difficult, and despite the life-threatening nature of the disease it may remain unrecognized in at least some patients. The author explains that the disease should be easy to recognize when adequate samples are obtained in the acute crisis. The diagnosis is confirmed through mutation analysis in the HMGCS2 gene on chromosome 1p12.
منابع مشابه
Intracellular Localization of the 3-Hydroxy-3-methylglutaryl Coenzyme A Cycle Enzymes in Liver SEPARATE CYTOPLASMIC AND MITOCHONDRIAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME A GENERATING SYSTEMS FOR CHOLESTEROGENESIS AND KETOGENESIS*
Acetoacetyl-CoA thiolase and 3-hydroxy3-methylglutaryl coenzyme synthase which comprise the 3-hydroxy3-methylglutaryl-CoA-generating system(s) for hepatic cholesterogenesis and ketogenesis exhibit dual mitochondrial and cytoplasmic localization. Twenty to forty per cent of the thiolase and synthase of avian and rat liver are localized in the cytoplasmic compartment, the remainder residing in th...
متن کاملSuccinylation and inactivation of 3-hydroxy-3-methylglutaryl-CoA synthase by succinyl-CoA and its possible relevance to the control of ketogenesis.
Succinyl-CoA (3-carboxypropionyl-CoA) inactivates ox liver mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5) in a time-dependent manner, which is partially prevented by the presence of substrates of the enzyme. The inactivation is due to the enzyme catalysing its own succinylation. Complete inactivation corresponds to about 0.5 mol of succinyl group bound/mol of enzyme dimer. T...
متن کاملIdentification of 3-methylglutarylcarnitine. A new diagnostic metabolite of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency.
Deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) lyase affects the metabolism of leucine as well as ketogenesis. This disorder is one of an increasing list of inborn errors of metabolism that presents clinically like Reye's Syndrome or nonketotic hypoglycemia. Four patients with proven 3-hydroxy-3-methylglutaryl-CoA lyase deficiency were shown to excrete a new diagnostically specific m...
متن کاملSome properties of 3-hydroxy-3-methylglutaryl-coenzyme A synthase from ox liver.
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5) was purified from ox liver, and obtained essentially free from 3-oxoacyl-CoA thiolases. The kinetic behaviour, like that of the synthases from chicken liver and yeast, is compatible with a reaction pathway involving condensation of an acetyl-enzyme with acetoacetyl-CoA. The Km for acetoacetyl-CoA, less than 1 micronM at pH 7.8, ...
متن کاملLocalization of the gene encoding 3-hydroxy-3-methylglutaryl-coenzyme A synthase to human chromosome 5.
A series of hybrids between primary human cells and a Chinese hamster somatic cell mutant (Mev-1), defective in expression of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase [(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating, EC 4.1.3.5], has been prepared that complements the mutant defect. A technique based on differential sensitivity of this enzyme...
متن کامل