Cholesterol balance

MANY FACTORS INFLUENCE THE CHOLESTEROL BALANCE IN TISSUES... 

In tissues, cholesterol balance is regulated as follows (Figure 26-5) Cell cholesterol increase is due to uptake of cholesterol-containing Hpoproteins by receptors, eg, the LDL receptor or the scavenger receptor uptake of free cholesterol from cholesterol-rich hpoproteins to the cell... 

Figure 26-5. Factors affecting cholesterol balance at the cellular level. Reverse cholesterol transport may be initiated by pre 3 HDL binding to the ABC-1 transporter protein via apo A-l. Cholesterol is then moved out of the cell via the transporter, lipidating the HDL, and the larger particles then dissociate from the ABC-1 molecule. (C, cholesterol CE, cholesteryl ester PL, phospholipid ACAT, acyl-CoA cholesterol acyltransferase LCAT, lecithinicholesterol acyltransferase A-l, apolipoprotein A-l LDL, low-density lipoprotein VLDL, very low density lipoprotein.) LDL and HDL are not shown to scale.

Feldman, E.B., Russell, B.S., Schnare, F.H., Miles, B.C., Doyle, E.A., and Moretti-Rojas, I. 1979a. Effect of tristearin, triolein and safflower oil diets on cholesterol balance in rats. J. Nutr. 109, 2226-2236. 

Fazio S, Linton MF. The inflamed plaque Cytokine production and cellular cholesterol balance in the vessel wall. Am J Cardiol 2001 88 12E-15E. 

Tab. 3.8 Cholesterol balance (supply/consumption per day) under normal conditions...

Fig. I. Overall scheme for cholesterol balance across the intestinal epithelial cell. After digestion, lipids in the intestinal lumen combine with bile acids to form mixed micelles (MM) that promote uptake into the intestinal epithelial cell. Within the intestinal cell, triglyceride and cholesterol, along with specific apoproteins, are synthesized into the chylomicron (CM) which, ultimately, delivers much of the triglyceride to peripheral organs and most of the cholesterol to the liver. Also shown in this diagram are the 3 major sources for epithelial cell cholesterol including (1) uptake from the lumen, (2) synthesis from acetyl-CoA and (3) uptake of low-density lipoproteins (LDL) by both receptor-dependent and receptor-indqjendent mechanisms.

It may be argued that there are important gaps in the contents of this volume. For instance, full discussions of the role of compartmentation of sterols and their metabolism, of the dynamics of cholesterol balance, etc. are lacking. We as editors take full responsibility for this. Our only excuse is that the material contained in the volume is already at the limit of what can be accommodated in a volume of New Comprehensive Biochemistry. 

Introduction of the statins in the mid-1980s transformed cholesterol management [38]. Isolated from the culture broths of penicilhns in the 1970s, they proved to be specific, competitive inhibitors of HMG CoA reductase (3-hydoxy 3-methylglutaryl coenzyme A reductase). This enzyme converts HMG CoA into mevalonate, the first committed step in cholesterol synthesis and an important site of metabolic control. The reduction in hepatic cholesterol synthesis (approximately 40% in vivo) results in up-regulation of LDL receptor activity with binding and uptake of plasma LDL to restore hepatic cholesterol balance. The activity of the LDL receptor is a major determinant of plasma cholesterol levels. These mechanisms are now well understood at a molecular level. 

Fig.l Cholesterol balance study in a type II patient treated with the soybean diet. Following the change from a low lipid diet with animal proteins to the soybean diet, there is a remarkable drop of plasma cholesterol levels without, however, changes either in- fecal steroid output or in the slope of the cholesterol specific activity decay curve (from Fumagalli, et al., 1982)... 

W.E. Connor, D.T. Witiak, D.B. Stone, and M.L. Armstrong, Cholesterol balance and fecal neutral steroid and bile acid excretion in normal men fed dietary fats of different fatty acid composition, J. Clin. Invest. 48 1363 (1969). 

Fig. 2. The two homeostatic mechanisms for maintaining cholesterol balance after absorbing dietary cholesterol are 1) decreasing endogenous synthesis, or 2) increasing fecal excretion. If these are defective then body cholesterol accumulates in either 3) plasma, or 4) extra-vascular tissues.

Cholesterol balance in cells is maintained by a number of factors (Table 7.6). In fact, it has been found that uptake of lipoproteins may influence cholesterol synthesis itself via the LDL receptor mechanism described in section 5.3.5(g). 

As we have seen in this chapter steroids have a number of functions in human physiology Cholesterol is a component part of cell mem branes and is found in large amounts in the brain Derivatives of cholic acid assist the digestion of fats in the small intestine Cortisone and its derivatives are involved in maintaining the electrolyte balance in body fluids The sex hormones responsible for mascu line and feminine characteristics as well as numerous aspects of pregnancy from conception to birth are steroids... 

Write a balanced, stoichiometric reaction for the synthesis of cholesterol from acetyl-CoA. 

HLB (hydrophile-lipophile balance) system, 70 126 HLB value, 72 54, 55 HMG-CoA, role in cholesterol synthesis, 5 142... 

Interpretation/results The absence of cholesterol, combined with the presence of one of its degradation products, A3,5-cholestadiene, indicates that the animal fat had been heated, perhaps as a means of bleaching. Given the mass balance of organic compounds, a significant level of inorganics must be present. 

Steroids are derived bio synthetically from cholesterol. They play multiple roles in human physiology sex characteristics, control of inflammation, embryo implantation, and control of salt and water balance. Cholesterol itself is an indispensable constituent of biological membranes. 

Binding of bile acids and their removal from the organism disturbs the balance of cholesterol and bile acids, and a compensatory increase of the transformation of cholesterol into... 

The effect of additives betrays the intricacy of the balance of rate effects even more. The addition of cholesterol to catalytic bilayers has been found to be beneficial for the Kemp eleminiation but to inhibit the decarboxylation of 6-NBIC. In general, the effects of additives on the decarboxylation of 6-NBIC appear to subtly depend on the structure of the hydrophobic tail and hydrophilic headgroup of additives. Similarly subtle effects were found for the Kemp elimination and nucleophilic attack by Br and water on aromatic alkylsulfonates depending on the choice of additive, hydrogen bonding effects, reactivity of partially dehydrated OH , and local water concentrations all played a role and vesicular catalysis could be increased or decreased. 

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