Cholesterol HMG-CoA reductase

Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme in the cholesterol biosynthetic pathway (Fig. 1). In contrast to desmosterol and other late-stage lipid-soluble intermediates, HMG is water-soluble, and there are alternative metabolic pathways for its breakdown when HMG-CoA reductase is inhibited so that there is no buildup of potentially toxic precursors. Therefore, of the more than 30 enzymes involved in the biosynthesis of cholesterol, HMG-CoA reductase was a natural target. Substances that have a powerful inhibitory effect on this enzyme, including ML236B (compactin), were first discovered by Endo in a fermentation broth of Penicillium citrinum in the... 

A coupling appears to exist between the rate-limiting enzyme in the biosynthesis of cholesterol, HMG-CoA reductase, and cholesterol 7a-hydroxylase. The two enzymes seem to be located close to each other on the endoplasmic reticulum membrane [66], and the two activities covariate under most conditions. Results from both in vivo and in vitro experiments show that newly synthesized cholesterol is the preferred substrate for cholesterol 7a-hydroxylase. In an early study by Staple and Gurin, it was shown that the bile acids in bile had a higher radioactivity than cholesterol after administration of labelled acetate to rats [67]. Bjorkhem and Danielsson found that the specific radioactivity of 7a-hydroxycholesterol was higher than that of cholesterol after incubation of labelled mevalonate with the 10000 x g supernatant fluid of a rat liver homogenate [50]. Balasubramaniam et al. showed that 7a-hydroxycholesterol isolated from the livers of rats after intravenous administration of labelled cholesterol had a lower specific radioactivity than cholesterol [58]. Cronholm and collaborators measured the incorporation of isotope from [1- H2]-,... 

Cholesterol, HMG-CoA reductase, triglycerides, LDL, HDL, HDL-apolipoprotein, cortisol, ACTH, testosterone, urine 17-OH-corticosteroids Acetylcholinesterase, MAOa, MAOb, ACTH, cGMP, phenylethylamine, catecholamines, neuroimaging (MRI, MR spectroscopy, magnetization transfer imaging, T2 relaxation analysis, SPECT, PET, fMRI)... 

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