Polyunsaturated fatty acids metabolic transformation

Dhopeshwarkar GA, Subramanian C. Biosynthesis of polyunsaturated fatty acids in the developing brain 1. Metabolic transformations of intracraniaUy administered 1- C linolenic acid. Lipids 1976 11 67-71. 

Fig. 6. Three irnportam oxidative pathways for the metabolism of polyunsaturated fatty acids. A. The principal steps in the formation of prostaglandin endoperoxides from arachidonic acid. B. Likely mechanism for the formation of hydroperoxy cis.trans conjugated fatly acids by autooxidalion or by lipoxygena.sc.s. In the latter case, positional as well as stereospecificity arc normally found. The formed hydroperoxides may then be enzymatically transformed into leukotrienes (not shown) or to hydroxy acids. C. The enzymatic sequence in cytochrome P-450 mediated oxygenation. The first electron is donated from NADPH via the f lavoprotein (Fp) NADPH-cytochrome-P-450-reductase. while the second electron comes either from NADPH or NADH. In this way the monooxygenase enzymes inlrrxluce one oxygen from air into the substrate.

Monooxygenase metabolism of essential fatty acids has received comparatively little attention. DiAugustine and Fonts found that in liver microsomes, linoleic acid, linolenic acid and arachidonic acid induced spectral changes of type I, which are associated with metabolism, but the products were not identified [394]. These polyunsaturated fatty acids could be expected to be wl- and w2-hydroxylated like their saturated counterparts and to be transformed into hydroxylated cis,trans conjugated products by chemical peroxidation (autooxidation) as discussed above. Recent studies show that cytochrome P-450 can metabolise polyunsaturated fatty acids to a large extent by epoxidation. The epoxides are rapidly hydrolysed to vicinal diols by microsomal or soluble enzymes. 

Fatty acid saturation metabolism, so called biohydrogenation, is considered to be a detoxif ting metabolism of gut bacteria to transform toxic-free polyunsaturated fatty acids to less toxic-free saturated fatty acids. We have revealed the complex metabolic... 

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