HOMEOSTASIS OF CHOLESTEROL IN THE BODY, MECHANISMS OF ITS DISORDER, ROLE OF 7α-HYDROXYLASE

Abstract

It has been shown that in humans and animals, CS homeostasis occurs in accordance with the same formula: (СSendog + CSexog) – (CSexcr + BAexcr) = 0. But in herbivores, the positive balance of CS in the body is not occurs; a person creates it by consuming animal products, high-calorie foods and substrates for the synthesis of cholesterol. Like herbivores, it does not need constant intake of cholesterol from the food, the release of which from the body in the form of bile acids is also limited by 7α-hydroxylase activity. This point of view is supported by the fact that a person's daily need for cholesterol can be met by one of its biosynthesis. The paper provides information on the role of liver cholesterol homeostasis and the transformation of cholesterol into bile acids (BA) in the disturbance of homeostasis. Hydroxylation is the only process that irreversibly removes CS from membranes and LP-complexes. For the formation of BA, 60–80 % of the total cholesterol synthesized daily in the body is spent. The rate of the 7α-hydroxylase reaction is affected by the presence of hypercholesterolemia: in experimental animals and in patients with HCS, the rate of the 7α-hydroxylase reaction of the liver is sharply reduced, the rate of conversion of cholesterol to BA and its removal from the body is reduced. A role in atherogenesis of a decrease in the rate of 7α-hydroxylation with aging in humans has been shown. The fact is underlined that the release of cholesterol in the form of bile acids reflects the rate of its synthesis in the body. The formation of BA and the excretion of cholesterol is inhibited by insufficient intake of vitamin C and unsaturated fatty acids into the human body. It is concluded that it is necessary to search for and synthesize substances that enhance the conversion of cholesterol into bile acids and its excretion from the body. The combination of stimulators of bile acid synthesis and blockers of HMG-CoA reductase can significantly increase the effectiveness of treatment of patients with atherosclerosis.