Biosynthesis of Fatty Acids and Eicosanoids:- Fatty Acid Synthesis Occurs in the Cytosol of Many Organisms but in the Chloroplasts of Plants
In most higher eukaryotes, the fatty acid synthase com plex is found exclusively in the cytosol (Fig. 21–8), as are the biosynthetic enzymes for nucleotides, amino acids, and glucose. This location segregates synthetic processes from degradative reactions, many of which take place in the mitochondrial matrix. There is a corresponding segregation of the electron-carrying cofactors used in anabolism (generally a reductive process) and those used in catabolism (generally oxidative). Usually, NADPH is the electron carrier for anabolic reactions, and NAD serves in catabolic reactions. In hepatocytes, the [NADPH]/[NADP ratio is very high (about 75) in the cytosol, furnishing a strongly reducing environment for the reductive synthesis of fatty acids and other biomolecules. The cytosolic [NADH]/[NAD+] ratio is much smaller (only about 8x10-4), so the NAD-dependent oxidative catabolism of glucose can take place in the same compartment, and at the same time, as fatty acid synthesis. The [NADH]/[NAD+] ratio in the mitochondrion is much higher than in the cytosol, because of the flow of electrons to NAD from the ox idation of fatty acids, amino acids, pyruvate, and acetyl CoA. This high mitochondrial [NADH]/[NAD+] ratio favors the reduction of oxygen via the respiratory chain. In hepatocytes and adipocytes, cytosolic NADPH is largely generated by the pentose phosphate pathway (see Fig. 14–21) and by malic enzyme (Fig. 21–9a). The NADP-linked malic enzyme that operates in the carbon-assimilation pathway of C4 plants (see Fig. 20–23) is unrelated in function. The pyruvate produced in the reaction shown in Figure 21–9a reenters the mitochondrion. In hepatocytes and in the mammary gland of lactating animals, the NADPH required for fatty acid biosynthesis is supplied primarily by the pentose phosphate pathway (Fig. 21–9b).
In the photosynthetic cells of plants, fatty acid syn thesis occurs not in the cytosol but in the chloroplast stroma (Fig. 21–8). This makes sense, given that NADPH is produced in chloroplasts by the light reactions of photosynthesis:
Again, the resulting high [NADPH]/[NADP+] ratio provides the reducing environment that favors reductive anabolic processes such as fatty acid synthesis.
FIGURE 21–8 Subcellular localization of lipid metabolism. Yeast and vertebrate cells differ from higher plant cells in the compartmentation of lipid metabolism. Fatty acid synthesis takes place in the compart ment in which NADPH is available for reductive synthesis (i.e., where the [NADPH]/[NADP+] ratio is high). Processes in red type are covered in this chapter.
