Useful Information
Human 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1
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PDB Code 2P8U Target Class Oxidoreductases Target HMGCS1 Alias HMGCS, MGC90332 Disease Area/Function metabolism Date Deposited Mar 23 2007 Authors
About this structure
The cytosolic enzyme 3-hydroxy 3 methylglutaryl coenzyme A synthase 1 catalyses the condensation of acetyl coenzyme A (Ac-CoA) with acetoacetyl Coenzyme A to yield 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA). HMG CoA is further reduced by HMG CoA reductase. This rate determining step is targeted by a cholesterol lowering class of drugs, the statins. This essential mammalian pathway is important for cholesterol and prenoid synthesis.HMGCS1 gene expression is upregulated by the the antipsychotic drugs clozapine and haloperidol in cultured human glioma cells. Since several studies have reported on structural abnormalities, decreased myelination and oligodendrocyte dysfunction in post-mortem brains from schizophrenic patients HMGCS1 is one of the interesting etiological candidate targets in schizophrenia. The enzyme is widely expressed with highest expression found in liver and adrenal cortex. Furthermore, due to its location in the mevalonate pathway it may play a role in hypercholesterolanemia and atherosclerosis.
