O Ii

Thiolase or SCPx thiolase O

Bile acids


Figure 4 Peroxisomal fatty-acid (FA) ^-oxidation pathways. While saturated long-chain fatty acids (LCFA) are preferentially degrade in mitochondria, saturated very-long-chain fatty acids (VLCFA) and some LCFA are shortened by peroxisomal ^-oxidation. Degradation of pristanic acid, the product of phytanic acid a-oxidation, and the conversion of the cholesterol-derived 27-carbon bile-acid precursors dihydroxycholestanoic acid (DHCA) and trihydroxycholestanoic acid (THCA) to 24-carbon bile acids also require this pathway. The mechanism by which these substrates enter peroxisomes is unknown. Four enzymatic reactions serve to shorten the substrates by either two (LCFA, VLCFA) or three (pristanic acid, DHCA, THCA) carbon atoms. The 2-methyl group of the latter substrates is shown in brackets. SCPx thiolase refers to the thiolase activity of sterol carrier protein x.

which are neurotoxic if allowed to accumulate. These fatty acids undergo several cycles of peroxiso-mal ^-oxidation until they are between eight and 10 carbon atoms long, after which they go to the mitochondria for further catabolism. Degradation of xenobiotic fatty acyl-like compounds (e.g., sulphur-substituted fatty acids and many nonsteroidal anti-inflammatory drugs) takes place in peroxisomes. Oxidation of dicarboxylic acids (from the diet or from w-oxidation) and 2-methyl-branched-chain fatty acids (from the diet or from a-oxidation) also occurs in peroxisomes.

The peroxisomal ^-oxidation pathway also fulfils an important biosynthetic role. In the hepatic synthesis of bile acids from cholesterol, the aliphatic side chain, which resembles an a-methyl-branched-chain fatty acid, must be shortened. A single cycle of peroxisomal ^-oxidation will remove a three-carbon portion of the side chain, converting the 27-carbon bile acid precursors dihydroxycholestanoic and tri-hydroxycholestanoic acids into the 24-carbon primary bile acids chenodeoxycholate and cholate, respectively.

Food Allergies

Food Allergies

Peanuts can leave you breathless. Cat dander can lead to itchy eyes, a stuffy nose, coughing and sneezing. And most of us have suffered through those seasonal allergies with horrible pollen counts. Learn more...

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