| Alternative pathways of oxidation of fatty acids
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| Unsaturated fatty acids yield less FADH2 when they are oxidized
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| Unsaturated fatty acids are already partially oxidized, so less FADH2, and correspondingly less ATP, is produced by their oxidation. The double bonds in polyunsaturated fatty acids have cis geometry and occur at three-carbon intervals, whereas the intermediates in β-oxidation have trans geometry and the reactions proceed in two-carbon steps. The metabolism of unsaturated fatty acids therefore requires several additional enzymes, both to shift the position and to change the geometry of the double bonds.
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| Odd-chain fatty acids gain access to the TCA cycle via propionyl-CoA
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Figure 14.5 Metabolism of propionyl-CoA to succinyl-CoA. Propionyl-CoA from odd-chain fatty acids is a minor source of carbons for gluconeogenesis. The intermediate, methylmalonyl CoA, is also produced during catabolism of branched-chain amino acids . Defects in methylmalonyl-CoA mutase or deficiencies in vitamin B12 lead to methylmalonic-aciduria. |
| The oxidation of fatty acids with an odd number of carbons proceeds from the carboxyl end, like that of normal fatty acids, except that propionyl-CoA is formed by the last thiolase cleavage reaction. The propionyl-CoA is converted to succinyl-CoA by a multi-step process involving three
enzymes and the vitamins biotin and cobalamin (Fig. 14.5). The succinyl-CoA enters directly into the TCA cycle.
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| Branched-chain fatty acids must be catabolized, to acetyl CoA and propionyl CoA via α-oxidation
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| Figure 14.6 α-Oxidation of branched-chain phytanic acids. The first carbon of phytanic acids is removed as carbon dioxide. In subsequent cycles of β-oxidation, acetyl-CoA and propionyl-CoA are released alternately. |
| There is continuing debate among nutritionists about the health benefits of butter versus those of margarine in foods. |
| Comments. Butter is rich in saturated fatty acids and cholesterol, which are risk factors for atherosclerosis. Margarine contains no cholesterol, and is richer in unsaturated fatty acids. However, the unsaturated fatty acids in margarine are mostly the unnatural trans-fatty acids formed during the partial hydrogenation of vegetable oils. Trans-fatty acids affect plasma lipids in the same fashion as long-chain saturated fats, suggesting that there are comparable risks associated with the consumption of butter or margarine. The resolution of this issue is complicated by the fact that various forms of margarine, for example soft-spread and hard-block types, vary significantly in their content of trans-fatty acids. |
| Phytanic acids are branched-chain polyisoprenoid lipids found in plant chlorophylls. Because the β-carbon of phytanic acids is at a branch point, it is not possible to oxidize this carbon to a ketone. The first and essential step in catabolism of phytanic acids is microsomal α-oxidation to pristanic acid,
releasing the (α-)carbon-1 as carbon dioxide. Thereafter, as shown in Figure 14.6, acetyl-CoA and propionyl-CoA are released alternately and in equal amounts. Refsum's disease is a rare neurologic disorder, characterized by accumulation of phytanic acid deposits in nerve tissues as a result of a genetic defect in α-oxidation.
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