Cytosolic 3-hydroxy-3-methyl glutaryl coenzyme a synthase in rat brain: properties and developmental change.
The properties and developmental change in the activity of cytosolic 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) synthase in brain was examined and whether or not HMG-CoA lyase is present in cytosol and mitochondria from brain was determined. Although mitochondrial fractions contained significant HMG-CoA lyase activity, the enzyme activity was not detected in brain cytosol. The synthase activity was present in both mitochondrial and cytosolic fraction. The HMG-CoA synthesis by brain cytosol was optimal at pH 8.0 and did not require Mg2+ or exogenous acetoacetyl CoA. This indicates that brain cytosol can synthesize sufficient quantity of acetoacetyl CoA from acetyl CoA to be utilized for HMG-CoA synthesis. Our results also showed that the specific activity (nmol acetyl CoA incorporated/mg protein) of HMG-CoA synthase in brain cytosol was high (between 2-11 days of postnatal age) when the cholesterol content of brain is increasing rapidly, and the activity declined slowly thereafter. This suggests that in brain, cytosolic enzyme HMG-CoA synthase plays a role in the regulation of cholesterol synthesis.
D000105:Acetyl Coenzyme A / Q000031:analogs & derivatives / Q000494:pharmacology; D000214:Acyl Coenzyme A; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D003600:Cytosol / Q000201:enzymology; D004492:Edetic Acid / Q000494:pharmacology; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D007652:Oxo-Acid-Lyases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; C010667:acetoacetyl CoA; D000105:Acetyl Coenzyme A; D004492:Edetic Acid; D006904:Hydroxymethylglutaryl-CoA Synthase; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase; D008274:Magnesium