Steroid biosynthesis (Cholesterol Biosynthesis) is an anabolic metabolic pathway that produces steroids from simple precursors. It starts in the mevalonate pathway, (HMG-CoA reductase pathway, mevalonate-dependent (MAD) route, isoprenoid pathway), in humans, with Acetyl-CoA and Acetoacetyl-CoA as the first two building blocks. These are joined together via HMG-CoA synthase to produce hydroxy-3-methylgutaryl-CoA (HMG-CoA), which is then reduced to mevalonic acid via the enzyme HMG-CoA reductase. HMG-CoA reductase is the protein target of many cholesterol lowering drugs called statins. The mevaolonic acid is then phosphorylated by mevalonate kinase and subsequently decarboxylated to form isopentylpyrophosphate (IPP). IPP can also be isomerized to form dimethylallylpyrophosphate (DMAPP). Isopentenyl pyrophosphate and dimethylallylpyrophosphate donate isoprene units, which can be joined together to make farnesyl and geranylgeranyl intermediates. Specifically, three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Lanosterol is a tetracyclic triterpenoid, which is the compound from which all steroids are derived. 14-Demethylation of lanosterol by CYP51 eventually yields cholesterol. Cholesterol is the central steroid in human biology. It can be obtained from animal fats consumed in the diet or synthesized de novo (as described above). Cholesterol is an essential constituent of lipid bilayer membranes and is the starting point for the biosyntheses of bile acids and salts, steroid hormones, and vitamin D. Bile acids and salts, e.g., taurocholate, are mostly synthesized in the liver. They are released into the intestine and function as detergents to solubilize dietary fats. Steroid hormones are mostly synthesized in the adrenal gland and gonads. They regulate energy metabolism and stress responses (glucocorticoids such as cortisol), salt balance (mineralocorticoids such as aldosterone), and sexual development and function (androgens and estrogens such as estradiol).
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