HMG-CoA reductase

HMG-CoA reductase ( HMGCR, abbreviation for 3 - hydroxy-3- methylglutaryl coenzyme A reductase) is that of the enzyme which reduces in eukaryotes, the β -hydroxy- β - methylglutaryl -coenzyme A to mevalonate. In plants, mevalonate is the starting material for all built up from isoprene units compounds ( isoprenoids ). In man, the reaction is rate limiting for the synthesis of cholesterol. Inhibition of HMG -CoA reductase is therefore of great medical importance to lower cholesterol. The group of HMG- CoA reductase inhibitors include the class of statins, which are derived from the natural product lovastatin and its side chain is structurally related to the mevalonic acid.

There are two types of enzymes, depending on the cofactor NADH ( EC 1.1.1.88 ) or NADPH ( EC 1.1.1.34 ). The former is found almost exclusively in bacteria before, the latter in all living things.

Other Names

  • Hydroxymethylglutaryl coenzyme A reductase (reduced nicotinamide, adenine dinucleotide phosphate)
  • 3-hydroxy -3-methylglutaryl -CoA reductase,
  • Beta -hydroxy -beta- methylglutaryl coenzyme A reductase,
  • Hydroxymethylglutaryl CoA reductase (NADPH ),
  • S -3-hydroxy -3-methylglutaryl -CoA reductase,
  • NADPH - hydroxymethylglutaryl -CoA reductase,
  • HMGCoA reductase - mevalonate: NADP oxidoreductase ( CoA acetylating )
  • 3-hydroxy -3-methylglutaryl CoA reductase ( NADPH), and
  • Hydroxymethylglutaryl -CoA reductase ( NADPH2 ).

Catalyzed reaction

Regulation

The regulation of the HMG -CoA reductase is complex; it is carried out, inter alia, transcriptionally through transcription factors, which are obtained with the assistance of SCAP ( SREBP cleavage activating protein ) by MBTPS1 proteolytically of SREBPs ( sterol regulatory element binding protein). SCAP is inactive if it has cholesterol bound. With increasing concentration of cholesterol in the cell, the formation of HMG -CoA reductase therefore decreases; In addition, the enzyme is inhibited directly by binding of cholesterol and lanosterol particularly, another Mevalonatderivat. The HMG -CoA reductase can be reversibly phosphorylated by the AMP -activated protein kinase (AMPK ) and inactivates it - if a lot of AMP is present, which is the case for cellular energy depletion, the energy-intensive cholesterol synthesis is slowed down.

In cholesterol lack transcription of the genes, and thus the formation of HMG -CoA reductase increases again.

Other hormones have a regulatory effect on HMG -CoA reductase

  • Insulin ( stimulating )
  • Glucagon ( antagonist of insulin)
  • Thyroid hormones ( stimulating, although results from other Hypothyroidism, unclear reasons for elevated cholesterol levels in the blood)

The HMG -CoA reductase is the target of drugs known as statins to reduce cholesterol.

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