Triacylglycerol biosynthesis

Section 26 4 Phospholipids are intermediates in the biosynthesis of triacylglycerols from fatty acids and are the principal constituents of the lipid bilayer component of cell membranes... 

Phosphatidic acids not only are intennediates in the biosynthesis of triacylglycerols but also are biosynthetic precursors of other members of a group of compounds called phosphoglycerides or glycerol phosphatides. Phosphorus-containing derivatives of lipids are known as phospholipids, and phosphoglycerides are one type of phospholipid. 

Diacylglycerol is glycerol esterified to two fatty acids at the sn-1 and sn-2 positions. It is a membrane-embedded product of phospholipase C action and an activator of protein kinase C. It is also an intermediate in the biosynthesis of triacylglycerol, phosphatidyletha-nolamine and phosphatidylcholine. 

Phosphatidate Is the Common Precursor in the Biosynthesis of Triacylglycerols, Many Phosphoglycerols, Cardiolipin... 

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. 

Tijburg LBM, Geelen MJH, van Golde LMG Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phos-phatidylethanolamine in the liver. Biochim Biophys Acta 1989 1004 1. 

Two possible pathways for the biosynthesis of 2-AG have been proposed (1) a phospholipase C (PLC) hydrolysis of membrane phospholipids followed by a second hydrolysis of the resulting 1,2-diacylglycerol by diacylglycerol lipase or (2) a phospholipase Ai (PLA,) activity that generates a lysophospholipid, which in turn is hydrolyzed to 2-AG by lysophospholipase C (Fig. 5) (Piomelli, 1998). Alternative pathways may also exist from either triacylglycerols by a neutral lipase activity or lysophosphatidic acid by a dephosphorylase. The fact that PLC and diacylglycerol lipase inhibitors inhibit 2-AG formation in cortical neurons supports the contention that 2-AG is, at least predominantly, biosynthesized by the PLC pathway (Stella, 1997). However, a mixed pathway may also be plausible. 

Lamb RG, Koch JC, Bush SR. An enzymatic explanation of the differential effects of oleate and gemfibrozil on cultured hepatocyte triacylglycerol and phosphatidylcholine biosynthesis and secretion. Biochim Biophys Acta 1993 1165 299-305. 

As precursors for the biosynthesis of fats (lipogenesis), the adipocytes use triacylglycerols from lipoproteins (VLDLs and chylomicrons see p. 278), which are formed in the liver and intestines and delivered by the blood. Lipoprotein lipase [1], which is located on the inner surface of the blood capillaries, cleaves these triacylglycerols into glycerol and fatty acids, which are taken up by the adipocytes and converted back into fats. 

Transfer of an additional acyl residue to DAG forms triacylglycerols (enzyme diacyl-glycerol acyltransferase 2.3.1.20). This completes the biosynthesis of neutral fats. They are packaged into VLDLs by the liver and released into the blood. Finally, they are stored by adipocytes in the form of insoluble fat droplets. 

Malonyl-CoA, the first intermediate in the cytosolic biosynthesis of long-chain fatty acids from acetyl-CoA (see Fig. 21-1), increases in concentration whenever the animal is well supplied with carbohydrate excess glucose that cannot be oxidized or stored as glycogen is converted in the cytosol into fatty acids for storage as triacylglycerol. The inhibition of carnitine acyltrans-ferase I by malonyl-CoA ensures that the oxidation of... 

We first describe the biosynthesis of fatty acids, the primary components of both triacylglycerols and phospholipids, then examine the assembly of fatty acids into triacylglycerols and the simpler membrane phospholipids. Finally, we consider the synthesis of cholesterol, a component of some membranes and the precursor of steroids such as the bile acids, sex hormones, and adrenocortical hormones. 

T Biosynthesis and degradation of triacylglycerols are regulated such that the favored path depends on the metabolic resources and requirements of the moment. The rate of triacylglycerol biosynthesis is profoundly altered by the action of several hormones. Insulin, for example, promotes the conversion of carbohydrate to triacylglycerols (Fig. 21-19). People with severe diabetes mellitus, due to failure of insulin secretion or action, not only are unable to use glucose properly but also fail to synthesize fatty acids from... 

FIGURE 21-18 Phosphatidic acid in lipid biosynthesis. Phosphatidic acid is the precursor of both triacylglycerols and glycerophospholipids. The mechanisms for head-group attachment in phospholipid synthesis are described later in this section. 

Glycerol 3-phosphate is required for the biosynthesis of tria-cylglycerols. Adipocytes, specialized for the synthesis and degradation of triacylglycerols, cannot use glycerol directly, because they lack glycerol kinase, which catalyzes the reaction... 

Familial adenomatous polyposis 574 Faraday, numerical value of 283 Farnesyl group 402, 559 Fat(s). See also Triacylglycerol (triglyceride) composition of 380 hydrolysis of 507 Fatty acid(s) 380-382 activation of 512 acyl CoA, derivatives of 507 biosynthesis of 722 branched chain 381 cyclopropane-containing 399 essential 721 in lipids 380 names of, table 380 oxidation 511 pKa values of 380 stability of 589... 

Figure 21-4 Biosynthesis of triacylglycerols, glycol ipids, and major phospholipids that are formed both in prokaryotes and eukaryotes. More complete schemes of phospholipid synthesis are shown in Figs. 21-3 and 21-5. Green arrow pathway occurring only in eukaryotes.

Figure 21-5 A more complete outline of the biosynthesis of triacylglycerols, glycolipids, and phospholipids including characteristic eukaryotic pathways. Green lines indicate pathways utilized by both bacteria and eukaryotes. Structures of some of the compounds are shown in Fig. 21-4. The gray arrows show the formation of phosphatidylserine by exchange with ethano-lamine (Eq. 21-10).

Outline of pathways for the biosynthesis of major cellular lipids (other than cholesterol) in a mammalian cell. Most of the metabolism of these lipids occurs on membrane surfaces because of the insoluble nature of the substrates and products. These lipids play three major roles (l) they act as a storehouse of chemical energy, as with triacylglycerols (2) they are structural components of membranes (boxed compounds) and (3) they act as regulatory compounds (underlined), either as eicosanoids, which act as local hormones, or as phosphorylated inositols and diacylglycerols, which function as second messengers. 

---