Cholesterol and fatty acid

Konrad E. Bloch, Feodor Lynen medicine, physiology discoveries concerning mechanism and regulation of cholesterol and fatty acid metabohsm... 

Spady DK, Woollett LA, Dietschy JM Regulation of plasma LDL-cholesterol levels by dietary cholesterol and fatty acids. Annu RevNutr 1993 13 355. 

Acetyl coenzyme A is the precursor of both cholesterol and fatty acids 39 Phosphatidic acid is the precursor of all glycerolipids 42 Sphingolipids are biosynthesized by adding head groups to the ceramide moiety 44... 

CN097 Satchithanandam, S., M. Reicks, R. J. Calvert, M. M. Cassidy, and D. Kritchevsky. Coconut oil and sesame oil affect lymphatic absorption of cholesterol and fatty acids in rats. J Nutr 1993 123(11) 1852-1858. 

Hemotoxic activity. Seed oil, administered orally to human adults, produced thrombocytosis in children, the effect was inactivated by ultraviolet radiation . Hypercholesterolemic activity. Seed oil, administered by gastric intubation to rabbits at a dose of 0.4 g/kg, was inactive " . Male Wistar rats fed 12 or 24% sesame oil in the diet for 4 weeks were investigated. The rats on the 24% sesame oil diet had significantly lower lymphatic cholesterol and fatty acids . 

Lithium blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin (Kleiner et ah, 1999). This results in a decrease in circulating T4 and T3 concentrations and a feedback increase in serum thyrotropin concentration. It also inhibits thyrotropin-stimulated adenylate cyclase activity (Kleiner et ah, 1999). Lithium has varying effects on carbohydrate metabolism. Increased and decreased glucose tolerance and decreased sensitivity to insulin have been observed (Van derVelde Gordon, 1969). In animals, lithium decreases hepatic cholesterol and fatty acid synthesis. 

ALTERNATE PROTOCOL 2 ENZYMATIC MEASUREMENT OF CHOLESTEROL Test combination kits for enzymatic determination of cholesterol in food are now commercially available. For the determination of total cholesterol, esterified cholesterol is hydrolyzed to free cholesterol and fatty acid under mild alkaline conditions. Cholesterol oxidase oxidizes free cholesterol to cholest-4-en-3-one to generate hydrogen peroxide, which further oxidizes methanol to formaldehyde. Formaldehyde then reacts with acetyl acetone in the presence of NH4+ ions to form yellow lutidine dye, which is subsequently determined spectrophotometric al 1 y. 

Some cholesterol entering from the diet may be esterified to various fatty acids, although the extent of esterification is variable. For example, egg yolk cholesterol is about 10% esterified (Bitman and Wood, 1980 Tattrie, 1972) cholesterol in meat and poultry is at least 50% esterified (Kritchevsky and Tepper, 1961). Esterified cholesterol entering the intestinal tract is mostly hydrolyzed by pancreatic enzymes, yielding free cholesterol and fatty acids (Howies et al., 1996). Only unesterified cholesterol is available for absorption. 

Basmacioglu, H., Cabuk, M., Unal, K., Ozkan, K., Akkan, S. and Yalcin, H. (2003) Effects of dietary fish oil and flax seed on cholesterol and fatty acid composition of egg yolk and blood parameters of laying hens. South African Journal of Animal Science 33, 266-273. 

We are interested in ACAT-1 inhibitors, which are expected to affect macrophages directly. In the early stages of atherosclerogenesis, macrophages penetrate the intima, efficiently take up modified LDL, store cholesterol and fatty acids as a form of neutral lipids such as CE and TG in the cytosolic lipid droplets, and are converted into foam cells, leading to the development of atherosclerosis in the arterial wall. We established an assay system of lipid droplet formation using intact mouse macrophages and searched for microbial inhibitors of the for-... 

At physiological pH the long-chain ceramides of the horny layer barrier in the presence of cholesterol and fatty acids have been shown to have equal capacity to form lamellar lipid structures as have phospholipids.24,25 The chain length of the ceramides is to a great extent longer than 18 carbons, even up to 34 carbons in one of the chains, and this suggests close packing of the crystalline type at normal skin temperatures. 

In addition to restoring the clinical appearance of xerotic skin, lanolin can also accelerate the restoration of normal barrier function to normal skin that has been acutely perturbed. Elias and colleagues have demonstrated that lanolin accelerated epidermal barrier recovery following perturbation with acetone.41 Three percent lanolin not only significantly (p < 0.001) decreased the TEWL at 45 min, but also after 4 h compared to vehicle-treated sites (Table 25.1). However, the rate of barrier recovery of lanolin-treated sites between 45 min and 4 h was not significantly different compared to vehicle treatment. This indicates that lanolin has an immediate effect on restoring a permeability barrier and does not interfere with the process of lamellar body extrusion and lipid synthesis, which are required for continued recovery. The effect of 3% lanolin on barrier recovery was very similar to that of the optimized ratio of stratum corneum lipids (ceramides, cholesterol, and fatty acids).42,43... 

Very-Low-Density Lipoproteins (VLDL) are less dense than chylomicrons. They contain more protein, although lipids (fatty acids, cholesterol and phospholipid, in that order) still make up 90 to 95 percent of their weight. Low-density lipoproteins (LDLs) are about 85 percent lipid by weight and contain more cholesterol than any other kind of lipid. VLDL and LDL contain large amounts of Apolipoprotein B. The VLDL and LDL are sometimes referred to as bad cholesterol because elevated serum concentrations of these lipoproteins correspond with a high incidence of artery disease (stroke and heart disease). The LDLs carry cholesterol and fatty acids to sites of cellular membrane synthesis. 

Horton, J.D., Goldstein, J.L., Brown, M.S. 2002. SREBPs Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125-1131. 

LDL binds specifically to lipoprotein receptors on the cell surface. The resulting complexes become clustered in regions of the plasma membrane called coated pits. Endocytosis follows (see Fig. 13-3). The clathrin coat dissociates from the endocytic vesicles, which may recycle the receptors to the plasma membrane or fuse with lysosomes. The lysosomal proteases and lipases then catalyze the hydrolysis of the LDL-receptor complexes the protein is degraded completely to amino acids, and cholesteryl esters are hydrolyzed to free cholesterol and fatty acid. New LDL receptors are synthesized on the endoplasmic reticulum (ER) membrane and are subsequently reintroduced into the plasma membrane. The cholesterol is incorporated in small amounts into the endoplasmic reticulum membrane or may be stored after esterification as cholesteryl ester in the cytosol this occurs if the supply of cholesterol exceeds its utilization in membranes. Normally, only very small amounts of cholesteryl ester reside inside cells, and the majority of the free cholesterol is in the plasma membrane. 

Analytical methods for plant sterol analysis are commonly based on procedures used for cholesterol analysis. However, a significant shortcoming of these methods is the fact that cholesterol occurs only as free cholesterol and fatty acid esters. Therefore, the analytical methods optimized for cholesterol analysis are not suitable, or only suitable with some restrictions, for the analysis of conjugates found only in plants (SFs, SGs, and ASGs). Further, the methods described below only give the total amount of plant sterols and no information of the different sterol species found in the samples. However, if detailed information about the sterol composition is not required, and the amount of sterols to be analyzed is sufficiently high for these less sensitive but simpler methods, they provide a less laborious alternative for the analysis. 

Methylmalonyl CoA arises directly as an intermediate in the catabolism of valine, and is formed by the carboxylation of propionyl CoA arising in the catabolism of isoleucine, cholesterol, and fatty acids with an odd number of carbon atoms. Normally, as shown in Figure 10.13, it undergoes an adeno-sylcobalamin-dependentrearrangementto succinyl CoA, catalyzed by methylmalonyl CoA mutase. In vitamin B12 deficiency, the activity of this enzyme is greatly reduced, although there is induction of the apoenzyme to some 1.5- to 5-fold above that seen in control animals. 

The best-known cholesterol esterase (Table I) is also a pancreatic enzyme. Cholesterol esterases not only hydrolyze cholesterol esters but also synthesize them from cholesterol and fatty acid in a reversible reaction. This is important in the digestion of cholesterol itself because... 

Pancreatic and Intestinal wall esterases break down cholesterol esters to free cholesterol and fatty acids. 

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