tricarboxylic acid; PC = pyruvate carboxylase; PDH = pyruvate dehydrogenase.
E. Further elongation
Although palmitate, a 16-carbon, fully saturated LCFA (16:0), is the primary end product of FAS activity, it can be further elongated by the addition of two-carbon units to the carboxylate end primarily in the smooth endoplasmic reticulum (SER). Elongation requires a system of separate enzymes rather than a multifunctional enzyme. Malonyl CoA is the two-carbon donor, and NADPH supplies the electrons. The brain has additional elongation capabilities, allowing it to produce the very-long-chain fatty acids ([VLCFA] over 22 carbons) that are required for synthesis of brain lipids.
F. Chain desaturation
Enzymes (fatty acyl CoA desaturases) also present in the SER are responsible for desaturating LCFA (that is, adding cis double bonds). The desaturation reactions require oxygen (O2), NADH, cytochrome b5, and its flavin adenine dinucleotide (FAD)-linked reductase. The fatty acid and the
NADH get oxidized as the O2 gets reduced to H2O. The first double bond is typically inserted between carbons 9 and 10, producing primarily oleic acid, 18:1(9), and small amounts of palmitoleic acid, 16:1(9). A variety of polyunsaturated fatty acids can be made through additional desaturation combined with elongation.
Humans have carbon 9, 6, 5, and 4 desaturases but lack the ability to introduce double bonds from carbon 10 to the ω end of the chain. This is the basis for the nutritional essentiality of the polyunsaturated ω-6 linoleic acid and ω-3 linolenic acid.
G. Storage as triacylglycerol components
Mono-, di-, and triacylglycerols consist of one, two, or three molecules of fatty acid esterified to a molecule of glycerol. Fatty acids are esterified through their carboxyl groups, resulting in a loss of negative charge and formation of neutral fat. [Note: An acylglycerol that is solid at room temperature is called a fat. If liquid, it is an oil.] 1. Arrangement: The three fatty acids esterified to a glycerol molecule to form a TAG are usually not of the same type. The fatty acid on carbon 1 is typically saturated, that on carbon 2 is typically unsaturated, and that on carbon 3 can be either. Recall that the presence of the unsaturated fatty acid(s) decrease(s) the Tm of the lipid. An example of a TAG molecule is shown in Figure 16.12.
2.
Triacylglycerol storage and function: Because TAG are only slightly soluble in water and cannot form stable micelles by themselves, they coalesce within white adipocytes to form large oily droplets that are nearly anhydrous. These cytosolic lipid droplets are the major energy reserve of the body. [Note: TAG stored in brown adipocytes serve as a source of heat through nonshivering thermogenesis (see p. 79).] 3.