Triglyceride and Phospholipid Synthesis

Glycerol phosphate comes from glycerol not in adipose) or from dihydroxyacetone phosphate (in liver and adipose). Nitrogen-containing phospholipids are made from diglyceride. Other phospholipids are made from phosphatidic acid. 

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Lipogenesis, the synthesis of lipids from carbohydrate via acetyl-CoA, occurs almost exclusively in the liver cells and the fatty tissue, (s. fig. 3.9) According to lipid topogenesis (4), the enzymes involved in triglyceride and phospholipid synthesis are localized on the cytoplasmic surface of the endoplasmic reticulum. The level of hepatic synthesis is regulated primarily by the insulin-glucagon quotient, as described by R.H. Unger in 1971. 

Several different aspects of lipid metabolism have been studied in the liver with the help of radioautography. These include triglyceride and phospholipid synthesis and secretion (O. Stein and Stein, 1966a,b, 1967a, 1969) as well as chylomicron triglyceride and cholesterol metabolism (O. Stein and Stein, 1967c Stein et al., 1969). 

Mechanism of Action. Like the systemic azoles, clotrimazole and other topical antifungal azoles work by inhibiting the synthesis of key components of the fungal cell membrane that is, these drugs impair production of membrane sterols, triglycerides, and phospholipids.9 Loss of these components results in the membrane s inability to maintain intracellular homeostasis, leading to death of the fungus. 

Lowered levels of cholesterol, triglycerides, and phospholipid biosynthesis due to vanadium were discovered several years ago (see Refs. 3,4, and 14). It has recently been found that vanadate(V) at concentrations of 1 mM inhibits mevalonate synthesis, the rate limiting step in cholesterol biosynthesis159. In this instance the active form of the metal may be vanadyl(IV). 

Triglyceride and phospholipid formation. This figure depicts the formation of triacylglycerol from a-glycerolphosphate and fatty-acyl CoA. The formation of phosphatidylethanolamine and phosphatidylcholine from scratch (i.e., from serine and methionine methyl groups) is also shown. The formation of phosphatidylcholine, starting with choline, is also depicted and is the major pathway for phosphatidylcholine synthesis. 

A molecular variation of plasma membrane has been reported by Puccia et al. Reduction of total lipids (XL) content and significant variations of triglyceride (TG) and phospholipids (PL) fractions were observed as a consequence of exposure of C. intestinalis ovaries to TBTCl solutions. In particular, an evident TG decrease and a PL increase were observed, which probably provoked an increment in membrane fluidity, because of the high concentration of long chain fatty acids and, as a consequence, PL. This could be a cell-adaptive standing mechanism toward the pollutants, as observed in Saccharomyces cerevisiae. Also the increase in the content of the polyunsaturated fatty acids (PUPA), important in the synthesis of compounds such as prostaglandin which are present in the ovary in a stress situation, was probably a consequence of a defense mechanism to the stress provoked by the presence of TBTCl. 

The primary developmental mechanism of the atherosclerotic process is not completely understood. It seems likely that the development of atherosclerosis is preceded by metabolic abnormalities of the synthesis, transport, and utilization of lipids. Lipids such as triglycerides and cholesterol esters are circulated in the blood in the form of particles (lipoproteins) wrapped in hydrophilic membranes that are synthesized from phospholipids and free cholesterol. Cholesterol is transported by particles of various sizes synthesized from triglycerides, cholesterol esters, and phospholipids, each of which plays a very specific role. 

The major biochemical changes observed are a striking depletion of ATP, impaired protein synthesis, defective incorporation of amino acids, and the appearance of RNA and proteins containing the ethyl rather than the methyl group. The plasma levels of triglycerides, cholesterol, lipoprotein, and phospholipid are all decreased. 

Nielsen, M.O., Jakobsen, K. 1994. Changes in mammary uptake of free fatty acids, triglyceride, cholesterol and phospholipid in relation to milk synthesis during lactation in goats. Comp. Biochem. Physiol. 109A, 857-867. 

Note that the enzymes CDP-choline 1,2-diacylglycerol transferase in phospholipid synthesis and acyl-CoA transferase in triglyceride synthesis have the common substrate 1,2-diacylglycerol thus we have this two-way synthesis shown in Fig. 13-13. 

Synthesis and metabolism of cholesterol, phospholipids, triglycerides and lipoproteins. 

Cholesterol and triglycerides, as the major plasma hpids, are essential substrates for cell membrane formation and hormone synthesis and provide a source of free fatty acids. Hyperlipidemia is defined as an elevation of one or more of cholesterol, cholesterol esters, phospholipids, or triglycerides. Lipids, being water immiscible, are not present in free form in the plasma but rather circulate as hpoproteins. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. The density of plasma lipoproteins is determined by their relative content of protein and lipid. Density, composition, size, and electrophoretic mobility divide lipoproteins into four classes (Table 21-1). 

Experiments carried out with Mucor mucedo (mildew) show that Terrazole inhibits, at the cellular level, the synthesis of triglycerides and sterol esters, stimulates that of free fatty acids and phospholipids,480 but does not appreciably affect nucleic add synthesis.481 Phospholipase is released in cell membranes and mitochondria the associated reduction in mitochondrial... 

Metabolic effects include interference with the biosynthesis of cystine and cholesterol, depression and stimulation of phospholipid synthesis and, at higher concentrations, inhibitions of serotonin oxidation. A 1981 study did not reveal any decrease in serum cholesterol or increase in serum triglycerides (Kiviluoto et al., 1981). 

Serum lipid concentrations vary during the menstrud cycle with serum cholesterol and phospholipid minimal at approximately the time of ovulation [227]. Serum lipids, triglycerides and cholesterol increase during pregnancy concomitantly with increased placental oestrogen synthesis [228, 229]. 

Plasma P-lipoprotein concentration in rats receiving orotic acid falls to less than 1% of normal and rebounds to normal level within 48 hours following withdrawal of orotic acid [300]. When perfused in situ, the livers from orotic acid fed rats released a-lipoprotein, albumin, and other plasma proteins but no detectable p-lipoprotein. They also released smaller amounts of cholesterol and phospholipids than normal livers and no triglycerides, although they contained ten times the normal amount of triglycerides [300]. Since p-lipoprotein has a specific role in the normal transport of triglycerides, the fatty liver produced by orotic acid appears to result from the inhibition of synthesis or release of hepatic P-lipoprotein. 

In the early stages of development of soybean seeds the lipid is virtually devoid of triglyceride and the main constituents are phospholipids and glycoli-pids. From the 9th day after flowering triglycerides are rapidly synthesized, coinciding with the onset of deposition of the lipid stores. Phospholipid synthesis continues throughout the period of deposition but at a low rate [144]. 

Synthesis of cholesterol, endogenous triglyceride, lipoproteins and phospholipids. It also catabolizes fatty acids and excretes the breakdown products of cholesterol metabolism in the bile. 

In this in vitro system, the presence of serum in cell culture medium is not necessary, but the type of transwell is important (the total amount of H-triglycerides secreted was two-fold higher when using 3 pm versus 1 pm pore size transwells), and oleic acid supplementation is required for the formation and secretion of CMs as well as the transport of 3-carotene through Caco-2 cells. Finally, the presence of Tween 40 does not affect CM synthesis and secretion in this in vitro cell culture system. Thus, CMs secreted by Caco-2 cells were characterized as particles rich in newly synthesized H-triglycerides (90% of total secreted) containing apolipoprotein B (30% of total secreted) and H-phospholipids (20% of total secreted) and with an average diameter of 60 nm. These characteristics are close to those of CMs secreted in vivo by enterocytes. ... 

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