Fatty acids branched chain

Whilst straight-chain fatty acids are the most common, branched-chain acids have been found to occur in mammalian systems, e.g. in wool fat and butter fat. They are also characteristic fatty acid constituents of the lipid part of cell walls in some 

The prostaglandins are a group of modified C20 fatty acids first isolated from human semen and initially assumed to be secreted by the prostate gland. They are now known to occur widely in animal tissues, but only in tiny amounts, and they have been found to exert a wide variety of pharmacological effects on humans and animals. They are active at very low, hormone-like concentrations and can regulate blood pressure, contractions of smooth 

Yet another variant for the metabolism of arachi-donic acid is the formation of leukotrienes, a series of fatty acid derivatives with a conjugated triene functionality, and first isolated from leukocytes. In a representative pathway (others have 

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D. V. Kinsman, "Branched-Chain Fatty Acids," in R. W. Johnson and E. Frit2, eds.. Fatty A.cids in Industry Marcel Dekker, Inc., New York, 1989,... 

In addition to unsaturated fatty acids, several other modified fatty acids are found in nature. Microorganisms, for example, often contain branched-chain fatty acids, such as tuberculostearic acid (Figure 8.2). When these fatty acids are incorporated in membranes, the methyl group constitutes a local structural perturbation in a manner similar to the double bonds in unsaturated fatty acids (see Chapter 9). Some bacteria also synthesize fatty acids containing cyclic structures such as cyclopropane, cyclopropene, and even cyclopentane rings. 

Although /3-oxidation is universally important, there are some instances in which it cannot operate effectively. For example, branched-chain fatty acids with alkyl branches at odd-numbered carbons are not effective substrates for /3-oxidation. For such species, a-oxidation is a useful alternative. Consider phy-tol, a breakdown product of chlorophyll that occurs in the fat of ruminant animals such as sheep and cows and also in dairy products. Ruminants oxidize phytol to phytanic acid, and digestion of phytanic acid in dairy products is thus an important dietary consideration for humans. The methyl group at C-3 will block /3-oxidation, but, as shown in Figure 24.26, phytanic acid a-hydroxylase places an —OFI group at the a-carbon, and phytanic acid a-oxidase decar-boxylates it to yield pristanie add. The CoA ester of this metabolite can undergo /3-oxidation in the normal manner. The terminal product, isobutyryl-CoA, can be sent into the TCA cycle by conversion to succinyl-CoA. 

FIGURE 24.26 Branched-chain fatty acids are oxidized by o -oxidation, as shown for phytanic acid. The product of the phytanic acid oxidase, pristanic acid, is a suitable substrate for normal /3-oxidation. Isobutyryl-CoA and propionyl-CoA can both be converted to suc-cinyl-CoA, which can enter the TCA cycle. 

Saturated fatty acids may be envisaged as based on acetic acid (CId3—COOH) as the first member of the series in which —CHj— is progressively added between the terminal CHj— and —COOH groups. Examples are shown in Table 14-1. Other higher members of the series are known to occur, particularly in waxes. A few branched-chain fatty acids have also been Isolated from both plant and animal sources. 

Hafner, E.W., Holley, B.W., Holdom, K.S. et al. (1991) Branched-chain fatty acid requirement for avermectin production by a mutant of Streptomyces avermitilis lacking branched-chain 2-oxo acid dehydrogenase activity. Journal of Antibiotics (Tokyo), 44, 349-356. 

Duran, E., Komuniecki, R.W., Komuniecki, P.R., Wheelock, M.J., Klingbeil, M.M., Ma, Y.C. and Johnson, K.R. (1993) Characterization of cDNA clones for the 2-methyl branched-chain enoyl-CoA reductase. An enzyme involved in branched-chain fatty acid synthesis in anaerobic mitochondria of the parasitic nematode Ascaris suum. Journal of Biological Chemistry 268, 22391—22396. 

Refsum s disease AR Oxidation of branched chain fatty acids phytan-olyl CoA 2-hydroxylase in some cases Increase of branched-chain phytanic acid, especially in PNS myelin 1, 38, Ch. 40... 

Bifunctional protein deficiency. The enzyme defect involves the D-bifunctional protein. This enzyme contains two catalytic sites, one with enoyl-CoA hydratase activity, the other with 3-hydroxyacyl-CoA activity [13]. Defects may involve both catalytic sites or each separately. The severity of clinical manifestations varies from that of a very severe disorder that resembles Zellweger s syndrome clinically and pathologically, to somewhat milder forms. Table 41-6 shows that biochemical abnormalities involve straight chain, branched chain fatty acids and bile acids. Bifunctional deficiency is often misdiagnosed as Zellweger s syndrome. Approximately 15% of patients initially thought to have a PBD have D-bifunctional enzyme deficiency. Differential diagnosis is achieved by the biochemical studies listed in Table 41-7 and by mutation analysis. 

Fig. 21.15. Partial gas chromatogram of extracted lipids. Peaks Ci4 0 to Ci8 o> saturated straight fatty chain acids (FA) with 14 to 18 carbon atoms C45br and Ci7 r, iso- and anteiso- branched-chain fatty acids Ci8 i FA, mono-unsatu-rated CigtoOH-FA, hydroxylated form derived by bacterial hydration of the original oleic acid. (Reprinted/redrawn from Nature, 432, 35-36, Copyright 2004, Nature Publishing Group, with permission.)...

The fatty acids with an even number of carbon atoms most frequently involved in acylglycerols are palmitic, stearic, oleic and linoleic, while odd-numbered and branched chain fatty acids only occur infrequently. Animal acylglycerols contain mainly saturated fatty acids although many fish oils are... 

One could plunge into the steric problems posed by the mechanism of protein synthesis on the ribosome 25 26)> or consider the steric fit of the hormone insulin to its acceptor in the cell membrane 27>. Or one could delve into the beautiful intricacy of terpenoid, squalene and steroid metabolism, or get lost in double bond formation, or in the steric problems posed by the branched chain fatty acids and their derivatives 28-34). 

Maefarlane, G.T., Gibson, G.R., Beatty, J.H., and Cummings, J.H., Estimation of short-chain fatty acid production from protein by human intestinal bacteria based on branched-chain fatty acid measurements, F M5 Mfcroftfo/. Ecol., 101 81-88 (1992). 

Capsaicinoids Are Products of the Phenylpropanoid Pathway and the Branched Chain Fatty Acid Pathway... 

The intermediates for the branched chain fatty acid production have been detected in tissues [69], The saturated and desaturated forms of the branched chain acyl-ACP and acyl-CoA are in the same relative amounts as in the final capsaicinoid products, as demonstrated for two different cultivated species, habanero (C. chinense) and jalapeno (C. annuum). From these results the authors indicate that the desaturation step occurs prior to release from the FAS complex. 

Stored under continuous light, and placental extracts from non-pungent fruit could synthesize capsaicinoids if vanillylamine and isocapric acid are provided. Together, these results raise the possibility that the gene product at Pml is a regulatory gene or a structural gene upstream in either the phenylpropanoid pathway or the branched chain fatty acid pathway and not capsaicinoid synthase. 

Valproate, a simple branched-chain fatty acid, was first reported as a successful treatment for acute mania by Lambert and colleagues in 1966. Following this report, at least 16 uncontrolled trials consistently supported the observation that valproate has acute and long-term mood-stabilizing effects in patients with bipolar disorder (reviewed by Keck et al. 1992a). Recently, five double-blind controlled studies of valproate have been completed that provide definitive evidence of its efficacy in acute mania. 

Kinetic resolution of branched-chain fatty acids has been reported recently by Franssen et al. [24]. With the help of immobilised Candida antarctica lipase B, racemic 4-methyloctanoic acid (responsible for sheep-like and goat-like flavours in sheep and goat milk and cheese, respectively) was esterified with ethanol. Only the R ester could be obtained, whereas (S)-4-methyloctanoic acid was not converted (Scheme 22.1). 

The VLCFA as well as the branched-chain fatty acids phytanic acid and pristanic acid are extremely hydrophobic and practically insoluble in water. Their intracellular presence is in the form of coenzyme A esters. These acids are usually stored in lipid-containing tissues such as adipose tissue, but they may also be constituents of various physiologically important lipids such as myelin. In this respect, the VLCFA and the branched-chain fatty acids are abundant in many tissues/organs. 

Circulating VLCFA and branched-chain fatty acids are mainly present in an esterified form such as triglycerides, phospholipids, cholesterol esters and even car-... 

The saturated VLCFA and branched-chain fatty acids are stable compounds they are not likely to be destroyed by oxidative processes. In this respect, storage of samples does not require more precautions than freezing. 

Harwood, C.S. Canale-Parola, E. Properties of acetate kinase isozymes and a branched-chain fatty acid kinase from a spirochete. J. Bacteriol., 152, 246-254 (1982)... 

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... 

RGURE17-17 The a oxidation of a branched-chain fatty acid (phytanic add) in peroxisomes Phytanic acid has a methyl-substituted /3 carbon and therefore cannot undergo /3 oxidation. The combined action of the enzymes shown here removes the carboxyl carbon of phytanic acid, to produce pristanic acid, in which the /3 carbon is unsubstituted, allowing oxidation. Notice that /3 oxidation of pristanic acid releases propionyl-CoA, not acetyl-CoA. This is further catabolized as in Figure 17-11. (The details of the reaction that produces pristanal remain controversial.)... 

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