Precursors of steroid hormones

Cholesterol is doubtless the most publicized lipid, notorious because of the strong correlation between high levels of cholesterol in the blood and the incidence of human cardiovascular diseases. Less well advertised is cholesterol s crucial role as a component of cellular membranes and as a precursor of steroid hormones and bile acids. Cholesterol is an essential molecule in many animals, including humans, but is not required in the mammalian diet—all cells can synthesize it from simple precursors. 

Cholesterol is a component of cell membranes and is the precursor of steroid hormones and the bile salts. 

Although cholesterol is accepted as the major precursor of steroid hormones as a result of side-chain cleavage to pregnenolone (see below), research over the past decade or so has focused on the mechanisms by which steroidogenic tissues obtain cholesterol. It should be borne in mind that such tissues require cholesterol, not only for steroid synthesis but also for membrane synthesis, and hence require more of the precursor sterol than other tissues. Morris and Chaikoff [1] showed that the bulk of rat adrenal cholesterol was derived from circulating cholesterol, and later work revealed a similar state of affairs in humans. 

Cholesterol is an extremely important biological molecule that modulates the fluidity of animal cell membranes and is the precursor of steroid hormones (such as progesterone, testosterone, oestradiol and cortisol) and bile acids. Cholesterol is either derived from the diet or synthesised de novo. Regardless of the source, cholesterol is transported through the circulation in lipoprotein particles, as are cholesterol esters, the cellular storage form of cholesterol. The amount of cholesterol synthesised daily in the liver of a normal person is usually double that obtained from dietary sources. Other sites of cholesterol synthesis include the intestine, and the degree of production is highly responsive to cellular levels of cholesterol. Over 1.2 g of cholesterol is lost in the faeces daily in the form of free sterol or as bile acids. 

We now turn our attention to the synthesis of the fundamental lipid cholesterol. This steroid modulates the fluidity of animal cell membranes (Section 12.6.2) and is the precursor of steroid hormones such as progesterone, testosterone, estradiol, and cortisol. All 27 carbon atoms of cholesterol are derivedfrom acetyl CoA in a three-stage synthetic process (Figure 26.6). 

Cholesterol is a steroid component of eukaryotic membranes and a precursor of steroid hormones. The committed step in its synthesis is the formation of mevalonate from 3-hydroxy-3-methylglutaryl CoA (derived from acetyl CoA and acetoacetyl CoA). Mevalonate is converted into isopentenyl pyrophosphate (C5), which condenses with its isomer, dimethylallyl pyrophosphate (C5), to form geranyl pyrophosphate (Cjo)- The addition of a second molecule of isopentenyl pyrophosphate yields famesyl pyrophosphate (C15), which condenses with itself to form squalene (C30). 

Cholesterol (Fig. ID), which is the metabolic precursor of steroid hormones, is a major component of plasma membranes. Its fused ring system brings a greater rigidity than other membrane lipids. Cholesterol can be esterified on the C3 OH-group to long-chain fatty acids to form cholesteryl esters which are major components of lipoproteins. 

Table V. Precursors of Steroid Hormones (Timetable of Discovery)...

Cholesterol Itself and Isoprenold Intermediates In Its synthesis are biosynthetic precursors of steroid hormones, bile acids, llpid-soluble vitamins, and numerous other bloac-tlve molecules (see Figure 18-7). 

Major sterol in animals essential for cell membranes precursor of steroid hormones... 

Cholesterol is obtained from the diet and synthesized in most cells of the body. It is a component of cell membranes and the precursor of steroid hormones and of the bile salts used for fat absorption. High concentrations of cholesterol in the blood, particularly the cholesterol in lipoprotein particles called low density lipoproteins (LDL), contribute to the formation of atherosclerotic plaques. These plaques (fatty deposits on arterial walls) are associated with heart attacks and strokes. A high content of saturated fat in the diet tends to increase circulatory levels of LDL cholesterol and contributes to the development of atherosclerosis. 

Cholesterol A lipid substance that we both make and take in via our diet. Important component of membranes, lipoproteins, etc. but in excessive levels contributes to atherosclerotic plaques. Precursor of steroid hormones. 

Cholesterol (below, see also Section 23.4B) Is an alcohol that Is a precursor of steroid hormones and a vital constituent of cell membranes. It Is essential to life. On the other hand, deposition of cholesterol In arteries is a cause of heart disease and atherosclerosis, two leading causes of death in humans. For an organism to remain healthy, there has to be a delicate balance between the biosynthesis of cholesterol and its utilization, so that arterial deposition is kept at a minimum. 

Two observations suggest that cholesterol is a precursor of steroid hormones. First, cholesterol concentrations are high in the adrenal, and the cholesterol content of the endocrine gland decreases when the cortex is stimulated by ACTH. Second, by using a deuterium label. Block demonstrated that cholesterol is converted into pregnanediol, a compound readily isolated from urine of pregnant women [46, 47]. 

Although cholesterol may serve as a precursor of steroid hormones, investigators still debate whether or not cholesterol is a required or the only intermediate. Other compounds formed from squalene may serve as precursors of steroid hormones. The slow transfer of radioactivity from cholesterol to testosterone in testes slices obtained from animals stimulated by chorionic hormones indicates that intermediates other than cholesterol participate in steroid hormone biosynthesis. Whereas chorionic hormones markedly stimulate the incorporation of acetate into cholesterol, the specific activity of testosterone is not markedly increased. 

Cholesterol is an ubiquitous protoplasmic component in living organisms, a precursor of steroidal hormones and bile acids, and is synthesized in most tissues. Cholesterol undergoes constant turnover through degradation processes counterbalanced by exogenous supply and endogenous formation. 

Cholesterol Biosynthesis. Cholesterol is an essential structural component of animal cell membrane, required to establish proper membrane permeability and fluidity. It is also a precursor of steroid hormones (e.g., progesterone, testosterone, estradiol and cortisol), bile acids and vitamin D. Cholesterol is synthesized from acetyl-CoA in three stages and NADPH acts as the electron donor for the first stage during which 3-hydroxy-3-methylglutaryl CoA (HMG) is converted to mevalonate [20, 23],... 

Cholesterol is a steroid which stabilises cell membranes and is also a biosynthetic precursor of steroid hormones and bile salts. The accumulation of plaques on the walls of coronary and carotid arteries which have a high cholesterol content results in a condition... 

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