1,2.3-Triacylglycerol synthesis

Enzymes and regulation of TAG synthesis have been reviewed in depth by Coleman et al. (2000, 2004). 

For metabolism to occur, fatty acids must be activated to their acyl 

Interestingly, for maximum TAG synthesis, a preference was shown for palmitoyl-CoA as substrate for the initial acylation of glycerol-3-phosphate (Kinsella and Gross, 1973), apparently accelerating the rate of supply of substrate as acceptor for de novo-synthesized fatty adds, whereas oleic acid reduced total de novo synthesis, apparently by competing with butyryl CoA for the esterification of diacylglycerol (Hansen and Knudsen, 1987). 

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The regulation of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine biosynthesis is driven by the availability of free fatty acids. Those that escape oxidation are preferentiaUy converted to phos-phohpids, and when this requirement is satisfied they are used for triacylglycerol synthesis. 

Fatty acid and triglyceride (triacylglycerol) synthesis acetyl-CoA carboxylase and fatty acid synthase multi-enzyme complex... 

Figure 11.7 Synthesis of triaq/lglyceroL The precursors are glycerol 3-phosphate and long-chain acyl-CoA. R, is a saturated fatty acid, R2 is an unsaturated fatty acid (one or two doubte bonds) and R3 is either saturated or unsaturated. The activity of GPAT-1 regulates triacylglycerol synthesis. In all reactions involving RCO.SCoA, the CoASH is released but is not shown in this diagram. P,- - phosphate.

Fatty acid synthesis (provides acetyl-CoA) Fatty acid synthesis Fatty acid desaturation Triacylglycerol synthesis... 

FIGURE 21-19 Regulation of triacylglycerol synthesis by insulin. Insulin stimulates conversion of dietary carbohydrates and proteins to fat. Individuals with diabetes mellitus lack insulin in uncontrolled disease, this results in diminished fatty acid synthesis, and the acetyl-CoA arising from catabolism of carbohydrates and proteins is shunted instead to ketone body production. People in severe ketosis smell of acetone, so the condition is sometimes mistaken for drunkenness (p. 909). 

Synthesis of Fatty Acids from Glucose After a person has ingested large amounts of sucrose, the glucose and fructose that exceed caloric requirements are transformed to fatty acids for triacylglycerol synthesis. This fatty acid synthesis consumes acetyl-CoA, ATP, and NADPH. How are these substances produced from glucose ... 

Triacylglycerol synthesis acetyl-CoA---> fatty acids---> triacylglycerol... 

PA is the precursor of many other phosphoglycerides. The steps in its synthesis from glycerol phosphate and two fatty acyl CoAs were illustrated in Figure 16.14, p. 187, in which PA is shown as a precursor of triacylglycerol. [Note Essentially all cells except mature ery-. throcytes can synthesize phospholipids, whereas triacylglycerol synthesis occurs essentially only in liver, adipose tissue, lactating mammary glands, and intestinal mucosal cells.]... 

VLDLs are produced in the liver (Figure 18.17). They are composed predominantly of triacylglycerol, and their function is to carry this lipid from the liver to the peripheral tissues. There, the triacylglycerol is degraded by lipoprotein lipase, as discussed for chylomicrons (see p. 226). [Note "Fatty liver" (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic triacylglycerol synthesis and the secretion of VLDL. Such conditions include obesity, uncontrolled diabetes mellitus, and chronic ethanol ingestion.]... 

Increased triacylglycerol synthesis Triacylglycerol synthesis is favored because fatty acyl CoA is available both from de rxxo synthesis from acetyl CoA and from hydrolysis of the triacylglycerol component of chylomicron remnants removed from Ihe blood by hepatocytes (see p. 176). Glycerol 3-phosphate, Ihe... 

Glucose transport into the adipocyte and its subsequent metabolism are depressed owing to low levels of circulating insulin. This leads to a decrease in fatty acid and triacylglycerol synthesis. 

Decreased uptake of fatty acids In fasting, lipoprotein lipase activity of adipose tissue is low. Consequently, circulating triacyl-glycerol of lipoproteins is not available for triacylglycerol synthesis in adipose tissue. 

Glycogen synthesis Fatty acid synthesis Triacylglycerol synthesis VLDL synthesis... 

Table 2 Inhibition of Triacylglycerol Synthesis by DGAT Inhibitors in Assays Using Rat Liver Microsomes and Intact Raji Cells...

S Cases, S J Smith, Y-W Zheng, HM Myers, SR Lear, E Sande, S Novak, C Collins, CB Welch, AJ Lusis, SK Erickson, RV Farese Jr. Identification of a gene encoding an acyl CoA diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci (USA) 95 13018-13023, 1998. 

Hansen, H.O., Grunnet, I. and Knudsen, J. 1984a. Triacylglycerol synthesis in goat mammary gland. The effect of ATP, Mg2+ and glycerol 3-phosphate on the esterification of fatty acids synthesized de novo. Biochem J. 220, 513-519. 

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