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Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [3] [4]Cholesterol is biosynthesized by all animal cells [citation needed] and is an essential structural and signaling component of animal cell membranes.
Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In animals, these fats are obtained from food and are synthesized by the liver. [1]
Cholesterol synthesis pathway. More generally, this synthesis occurs in three stages, with the first stage taking place in the cytoplasm and the second and third stages occurring in the endoplasmic reticulum. [9] The stages are as follows: [12] 1. The synthesis of isopentenyl pyrophosphate, the "building block" of cholesterol 2.
HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, EC 1.1.1.88; NADPH-dependent, EC 1.1.1.34) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids.
Following up from that study the researchers explored a novel way to lower blood cholesterol levels without modifying the diet and lifestyle of subjects suffering with elevated blood cholesterol levels. The primary goal was to inhibit the cholesterol biosynthesis in the body. Hence HMG-CoA reductase (HMGR) became a natural target.
Cholesterol 7 alpha-hydroxylase is a cytochrome P450 heme enzyme that oxidizes cholesterol in the position 7 using molecular oxygen. It is an oxidoreductase. CYP7A1 is located in the endoplasmic reticulum (ER) and is important for the synthesis of bile acid and the regulation of cholesterol levels. [8] [10]
Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. The body produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis producing 400–600 mg daily. Human adults secrete between 12 and 18 g of bile acids into the intestine each day, mostly after meals.
Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its influence on metabolism. Examples of these lipids include cholesterol and triglycerides.