The conversion of HMG-CoA to mevalonate by HMG-CoA reductase is the rate-limiting step of cholesterol biosynthesis and is under strict regulatory control (see Figure 1 ). HMGR is the target of compounds that are effective in lowering serum cholesterol levels. Human HMG-CoA reductase consists of a single polypeptide chain of 888 amino acids. The amino-terminal residues are membrane bound and reside in the endoplasmic reticulum membrane, while the catalytic site of the protein resides in its cytoplasmic, soluble carboxy-terminal portion. A linker region connects the two portions of the protein.
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