Brain cholesterol biosynthesis

D. Bochelen, M. Mersel, P. Behr and P. Lutz, Effects of oxysterol treatment on cholesterol biosynthesis and reactive astrocyte proliferation in injured rat brain cortex, J. Neurochem. 65 (1995) 2194-2200. 

In addition to the liver and intestine (where cholesterol upon incorporation as lipoproteins reaches blood circulation), cholesterol biosynthesis occurs in almost all tissues. The rates of cholesterol synthesis may be high in organs or tissues, such as liver, developing brain, skin (epidermis), adrenal glands, and malignant tumors, or it may be low as in mature brain, kidney. 

B. Cholesterol Biosynthesis in the Brain in Vivo (Short-Term Experiments)... 

Gross et dl. (1960) examined the effect of various concentrations of chlorpromazine on cholesterol biosynthesis in the brain of 10-day-old rats. High concentrations of the drug (10 M) blocked the in vitro incorporation of l-C -acetate, G-C -glucose, and 2-C -mevalonate into brain cholesterol. Smaller doses of chlorpromazine appeared to stimulate... 

Histochemical, cytochemical, developmental, and biochemical studies indicate that much of the brain cholesterol is localized in the lipid-protein layers of the myelin sheath. As a result, this cholesterol is largely removed from the normal metabolic environment of the brain. Thus, although nervous tissue contains relatively large amounts of lipid, biosynthesis and the mean turnover rate of the typical myelin lipids including cholesterol are quite slow. Nevertheless dynamic metabolism may be found in small pools of, for example, cell or organelle membrane, cytoplasmic lipid, or outer parts of the myelin sheath. Such possibilities may serve to explain some of the various anomalous results reported by many workers studying brain cholesterol metabolism. 

The conversion of acetate-1- C to cholesterol by a variety of rat tissues has been studied in vitro. Efficiency of conversion is greatest in newborn skin, followed by newborn brain, liver, adult skin, intestine, testes, and kidney. The liver is generally assumed to be the major source of the plasma cholesterol, and this is the target organ of most studies designed to test various aspects of cholesterol biosynthesis. 

HMG is an important intermediate in cholesterol biosynthesis and this pathway provides a link between fatty acid and cholesterol metabolism. Ketone bodies are also excellent fuels for the liver and even brain during starvation, even though brain cannot utilize long chain fatty acids as fuels. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

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