Fatty acids, activation branched chain, metabolism

A second important difference between mitochondrial and peroxisomal fi oxidation in mammals is in the specificity for fatty acyl-CoAs the peroxisomal system is much more active on very-long-chain fatty acids such as hexacosanoic acid (26 0) and on branched-chain fatty acids such as phytanic acid and pristanic acid (see Fig. 17-17). These less-common fatty acids are obtained in the diet from dairy products, the fat of ruminant animals, meat, and fish. Their catabolism in the peroxisome involves several auxiliary enzymes unique to this organelle. The inability to oxidize these compounds is responsible for several serious human diseases. Individuals with Zellweger syndrome are unable to make peroxisomes and therefore lack all the metabolism unique to that organelle. In X-linked adrenoleukodystrophy (XALD), peroxisomes fail to... 

BCFAs make up the major proportion of fatty acids in the lipid extract from certain bacteria, such as bacilli [2]. Biosynthesis of BCFAs occurs with the branched-chain amino acids as primary precursors and malonyl-CoA (coenzyme A) as the chain extender (Figure 18.1). These BCFAs biosynthesized by bacteria and included in fermented food may contribute to the food s regulation of cell biology or metabolism [3-5]. A saturated BCFA, 13-methyltetradecanoic acid (13-MTD), was purified from a fermented soy product as an antitumor compound [6]. A BCFA was also found to induce apoptotic cell death in human cancer cells [6]. In this review, we describe the biological activities of BCFAs, with special reference to 13-MTD. 

Various pathways are employed for the degradation of branched-chain fatty acids, some of which arise from the metabolism of the branched-chain amino acids (see Leucine). Short-chain fatty adds are converted to their feitty acyl derivatives within the mitochondria, but long-chain fatty adds can be activated only by the endoplasmic reticulum and outer mi-tochondritd membrane. Long-chain acyl-CoA caimot penetrate the itmer mitochondrial membrane, and must be transported into the mitochondria as acyl-camitine (Fig. 3). 

In humans, methylmalonyl-CoA mutase is required for the metabolism of proprionate, derived from branched-chain amino acids, odd-chain fatty acids and cholesterol, into succinyl-CoA (Banerjee 1997 Pett et at. 2002). Methylmalonyl-CoA mutase requires AdoCbl as a cofactor. The mechanism involves the homolytic cleavage of the Co-C bond, forming cob(II)alamin and a 5 -deoxyadenosyl radical (Pett et at. 2002). The homolytic cleavage of the Co-C bond is increased 10 -fold in the presence of the enzyme. The 5 -deox-yadenosyl radical first abstracts a hydrogen atom from the substrate methyl-malonyl-CoA, which donates after a rearrangement reaction back to form succinyl-CoA (Pett et at. 2002). In humans, deficiency in methylmalonyl-CoA mutase causes an inherited metabolic disorder and is one of causes of methylmalonylacidemia. According to the severity of methylmalonyl-CoA mutase reduced activity, the deficiency is characterized as muf (detectable... 

The discovery of a novel pathway for biosynthesis of medium and short chain fatty acids in plants (a-keto acid elongation pathway, 1) raises the possibility (however unlikely) that medium-chain fatty acids (mcFAs) of certain oil seeds producing them may be derived by this pathway. Alternatively, these may be formed after release of elongating fatty acid chains from fatty acid synthase mediated biosynthesis (FAS) by specific medium chain thioesterases [2, 3,4]. Thus far the aKAE pathway is only known to occur in trichome glands of plants in the family Solanaceae. In the aKAE pathway, iso-, anteiso- or straight-chain keto acid products of branched-chain amino acid metabolism are elongated by one carbon (via acetate) per cycle. The final step is predicted to be oxidative decarboxylation to yield CoA activated acids. The mechanism that determines the chain length of aKAE products is not understood [1]. 

The metabolic pathway for the dissimilation of isoleucine has been derived largely from the results of experiments with variously C Mabeled 2-methylbut3rrate preparations (126) and confirmed by identification of the products of enzyme activity (127). The proposed scheme (Fig. 7) engenders confidence because it is in harmony with the established pathways for the catabolism of the other branched-chain amino acids and the fatty acid intermediates of this catabolism. 

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