Controlling Cholesterol Synthesis beyond 3-Hydroxy-3-methylglutaryl-CoA Reductase (HMGCR)

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the target of the statins, important drugs that lower blood cholesterol levels and treat cardiovascular disease. Consequently, the regulation of HMGCR has been investigated in detail. However, this enzyme acts very early in the cholesterol synthesi...

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Bibliographic Details
Published in:	The Journal of biological chemistry 2013-06, Vol.288 (26), p.18707-18715
Main Authors:	Sharpe, Laura J., Brown, Andrew J.
Format:	Article
Language:	eng
Subjects:	Alternative Splicing Animals Cholesterol Cholesterol - biosynthesis Cholesterol Regulation Endoplasmic Reticulum - metabolism ER-associated Degradation Humans Hydroxymethylglutaryl CoA Reductases - metabolism Minireviews NSDHL Post-translational Modification Protein Isoforms - metabolism Protein Processing, Post-Translational Squalene Monooxygenase Squalene Monooxygenase - metabolism SREBP Sterol Sterol Regulatory Element Binding Proteins - metabolism
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Summary:	3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the target of the statins, important drugs that lower blood cholesterol levels and treat cardiovascular disease. Consequently, the regulation of HMGCR has been investigated in detail. However, this enzyme acts very early in the cholesterol synthesis pathway, with ∼20 subsequent enzymes needed to produce cholesterol. How they are regulated is largely unexplored territory, but there is growing evidence that enzymes beyond HMGCR serve as flux-controlling points. Here, we introduce some of the known regulatory mechanisms affecting enzymes beyond HMGCR and highlight the need to further investigate their control.
ISSN:	0021-9258 1083-351X