Fatty acid biosynthesis, differences from steps

Although fatty acids are both oxidized to acetyl-CoA and synthesized from acetyl-CoA, fatty acid oxidation is not the simple reverse of fatty acid biosynthesis but an entirely different process taking place in a separate compartment of the cell. The separation of fatty acid oxidation in mitochondria from biosynthesis in the cytosol allows each process to be individually controlled and integrated with tissue requirements. Each step in fatty acid oxidation involves acyl-CoA derivatives catalyzed by separate enzymes, utihzes NAD and FAD as coenzymes, and generates ATP. It is an aerobic process, requiring the presence of oxygen. 

Cholesterol, like long-chain fatty acids, is made from acetyl-CoA, but the assembly plan is quite different. In early experiments, animals were fed acetate labeled with 14C in either the methyl carbon or the carboxyl carbon. The pattern of labeling in the cholesterol isolated from the two groups of animals (Fig. 21-32) provided the blueprint for working out the enzymatic steps in cholesterol biosynthesis. 

Fatty acid biosynthesis also occurs in steps of two carbon atoms. Biosynthesis takes place in the cytosol. In addition to occurring in a different cellular compartment from degradation, biosynthesis involves totally different enzymes and different coenzymes. 

Fatty acid synthesis in plants differs from that in animals in the following ways location (plant fatty acid synthesis occurs mainly in the chloroplasts, whereas in animals fatty acid biosynthesis occurs in the cytoplasm), metabolic control (in animals the rate-limiting step is catalyzed by acetyl-CoA carboxylase, whereas in plants, this does not appear to be the case), enzyme structure (the structures of plant acetyl-CoA carboxylase and fatty acid synthetase are more closely related to similar enzymes in E. coli than to those in animals). 

Guiet et al. (2003) demonstrated that deuterium (2H) distribution in fatty acids was non-statistical and could be related to isotopic discrimination during chain extension and desaturation. Petroselinic acid (C18 1A6) (Fig. 21.4), a fatty acid characteristic of the seeds of the Apiaceae, has been shown to be biosynthesized from palmitoyl-ACP (C16 0) by two steps, catalysed by a dedicated A4-desaturase and an elongase. The isotopic profile resulting from this pathway is similar to the classical plant fatty acid pathway, but the isotopic fingerprint from both the desaturase and elongase steps shows important differences relative to oleic and linoleic acid biosynthesis. 

It is clear that, to avoid metabolic chaos, biosynthetic pathways cannot use the same enzyme machinery as the corresponding catabolic ones. Sometimes, as in the synthesis of glucose from pyruvate (gluconeogenesis), this implies the use of alternative enzymes for only a few specific steps in the pathway, sometimes, as in the biosynthesis of fatty acids, the pathway is localised in a different cellular compartment from the catabolic pathway, and uses different enzymes. We now discuss each of these pathways in turn. 

C20H32O2, Mr 304.47, mp. -49.5 °C, bp. 163°C (133 Pa). A biochemically important essential fatty acid, precursor of various eicosanoids. In animals, A. is formed in several steps from linoleic acid by introduction of 2 double bonds and chain extension by 2 carbon atoms linoleic acid - y- linolenic acid - di-homo-y-linolenic acid arachidonic acid. In nature A. occurs in animal lipids, especially in phospholipids of cell membranes, from which phospholipase A2 releases A. on stimulation by hormones or mediators. A. serves as starting material for the biosynthesis of numerous physiologically active oxygen derivatives (especially hydroxy-, hydroperoxy-, and epoxy compounds) known as the eicosanoids. Their separation into different groups in the so-called A. cascade is shown in the figure... 

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