Isoleucine branched fatty acids from

Isoenzymes (isozymes) 536, 538 Isoionic point 106 Isolation of compounds 98-108 Isoleucine (He, I) 52s, 539 biosynthesis 540 branched fatty acids from 381 configuration 43 Isologous interactions 337-353 in oligomers 349 - 353 square 352s... 

Branched fatty acids of the anteiso series have a branch here and a 5-carbon "starter piece" derived from isoleucine... 

The methylmalonyl-CoA unit, which is the precursor to methyl-branched fatty acids and hydrocarbons, arises from the carbon skeletons of valine and isoleucine, but not succinate (Dillwith et al., 1982). Propionate is also a precursor to methylmalonyl-CoA, and in the course of these studies, a novel pathway for... 

The branched fatty acids the oxidation of which will be considered now are carbon compounds derived from amino acid metabolism. Isovalerate, methylbu-tyrate, and isobutyrate are related to the metabolism of leucine, isoleucine, and valine, respectively. The interest in the metabolism of branched fatty acids stems partly from the fact that the branched amino acids from which they are derived are precisely those that accumulate in maple syrup disease. 

One of the sex pheromone components of the housefly, Musca domestica, is Z9-21 H that is found on the cuticular surface of the fly. This compound is formed by the elongation of Z9-18 CoA using malonyl-CoA and NADPH to Z15-24 CoA which is decarboxylated to form Z9-21 Hc (Fig. 3) [78-80]. Other pheromone components include an epoxide and ketone that are produced from Z9-21 Hc by a cytochrome P450 [81,82] and methyl-branched alkanes that are produced by the substitution of methylmalonyl-CoA in place of malonyl-CoA at specific points during chain elongation [83,84]. A novel microsomal fatty acid synthase is involved in production of methyl-branched alkanes in most insects [85-87]. This fatty acid synthase is different from the ubiquitous soluble fatty acid synthase that produces saturated straight chain fatty acids in that it is found in the microsomes and prefers methylmalonyl-CoA. The amino acids valine and isoleucine can provide the carbon skeletons for methylmalonyl-CoA as well as propionate [83]. 

As discussed earlier, the avermectin polyketide backbone is derived from seven acetate and five propionate extender units added to an a branched-chain fatty acid starter, which is either (S( I )-a-mcthylbutyric acid or isobutyric acid. The C25 position of naturally occurring avermectins has two possible substituents a. sec-butyl residue derived from the incorporation of S(+)-a-methy lbutyry 1-CoA ( a avermectins), or an isopropyl residue derived from the incorporation of isobutyiyl-CoA ( b avermectins). These a branched-chain fatty acids, which act as starter units in the biosynthesis of the polyketide ring, are derived from the a branched-chain amino acids isoleucine and valine through a branched-chain amino acid transaminase reaction followed by a branched-chain a-keto acid dehydrogenase (BCDH) reaction (Fig. 5) [23]. 

Linear capsiacinoids with a C9/C12 chain are only trace constituents of capsicum oleoresin, which mainly contains branched capsaicinoids. The acyl moiety of these compounds is produced by the branched chain fatty acids pathway (Scheme 4.1) [30[. Depending on the nature of the amino acid that acts as the acyl starter precursor, different capsaicinoids are formed. Thus, capsaicinoids of the iso series such as CPS and homocapsaicin I are derived from valine and leucine via isobutyrylCoA and isovalerylCoA, respectively, while those from the anteiso series such as homocapsaicin II originate from isoleucine via 2-methylbutyrylCoA (Scheme 4.1) [31[. The polymethylene moiety of norcapsaicin has one less carbon than capsaicin. The... 

The liver also plays an essential role in dietary amino acid metabolism. The liver absorbs the majority of amino acids, leaving some in the blood for peripheral tissues. The priority use of amino acids is for protein synthesis rather than catabolism. By what means are amino acids directed to protein synthesis in preference to use as a fuel The K jyj value for the aminoacyl-tRNA synthetases is lower than that of the enzymes taking part in amino acid catabolism. Thus, amino acids are used to synthesize aminoacyl-tRNAs before they are catabolized. When catabolism does take place, the first step is the removal of nitrogen, which is subsequently processed to urea. The liver secretes from 20 to 30 g of urea a day. The a-ketoacids are then used for gluconeogenesis or fatty acid synthesis. Interestingly, the liver cannot remove nitrogen from the branch-chain amino acids (leucine, isoleucine, and valine). Transamination takes place in the muscle. 

Succinyl-CoA can also be synthesized from propionyl-CoA by way of methylmalonyl-CoA, which is formed in the oxidation of branched-chain amino acids (e.g., valine, isoleucine) and in the terminal stage of oxidation of odd-chain-length fatty acids (Chapter 18). Succinyl-CoA is utilized in the activation of acetoacetate (Chapter 18) and the formation of (5-aminolevulinate, a precursor of pro-phyrin (Chapter 29). 

In an analogous manner, a carboxyl group may also be transferred to propionyl-CoA (for the biosynthesis of branched or odd-numbered fatty acids, isoleucine synthesis, or cholesterol metabolism) or to 3-methylcrotonyl-CoA (a degradation product of leucine after addition of water, there results hydroxymethyl-glutaryl-CoA, the precursor of mevalonic acid cf. section 7.1.2). [117] Oxaloacetic acid is derived from pyruvate, which is of central importance for gluco-neogenesis. [108] In addition, biotin participates also in the transfer of carboxylic acid functions. In prokaryotes, biotin functions as a cofactor for decarboxylases (Tab. 7.6). 

Provided that the fatty acid contains an even number of C-atoms, it can be totally degraded to acetyl-CoA by p-oxidation. If the fatty acid contains an uneven number of C-atoms, however, the stepwise removal of two carbons at a time by p-oxidation eventually leads to a Cj compound, i.e. propionyl-CoA, which must be metabolized by alternative pathways. These pathways are shown in Rg.2 considerable quantities of propionyl-CoA also arise from the degradation of the branched-chain amino acids, isoleucine and valine (see L-leucine). The main pathway involves carboxylation of propionyl-CoA to methylma-lonyl-CoA, followed by the vitamin B]2-dependent isomerization of methylmalonyl-CoA to sucdnyl-... 

Propionic acid fermentation is not limited to propionibacteria it functions in vertebrates, in many species of arthropods, in some invertebrates imder anaerobic conditions (Halanker and Blomquist, 1989). In eukaryotes the propionic acid fermentation operates in reverse, providing a pathway for the catabolism of propionate formed via p-oxidation of odd-numbered fatty acids, by degradation of branched-chain amino acids (valine, isoleucine) and also produced from the carbon backbones of methionine, threonine, thymine and cholesterol (Rosenberg, 1983). The key reaction of propionic acid fermentation is the transformation of L-methylmalonyl-CoA(b) to succinyl-CoA, which requires coenzyme B12 (AdoCbl). In humans vitamin B deficit provokes a disease called pernicious anemia. 

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. 

In addition to the fatty acids with straight (unbranched) chains and an even number of C atoms, small amounts of acids with branched methyl groups or with an odd number of C atoms are also found in nature. Their metabolic fate in jS-oxi-dation is of considerable interest and can best be studied on the examples of the methyl branched C4- and the Ce-carboxylic acids. These two acids arise from the catabolism of the amino acids leucine, isoleucine, and valine by transamination and oxidative decarboxylation, as described in Chapt. VIII-10. Basically only two situations need to be discussed one with a methyl group in the a-position, or potentially in a-position (i.e. by repeated shortening of the chain by two C atoms the methyl group eventually ends up in a-position) the other with a methyl group in the -position, or at least potentially in /3-position. 

Modifications of the breakdown are necessitated by methyl branching. Branched-chain fatty acids arise also from the amino acids leucine, isoleucine, and valine (cf. Chapt. XII-5). Propionyl-CoA (instead of acetyl-CoA), is formed from isoleucine and valine, and this is converted to succinate by carboxylation and isomerization. 

The major fatty acids in most gram-positive and some gram-negative genera are branched chain iso or anteiso fatty acids. The Type II FAS enzymes present in these bacteria make use of primers different from the usual acetyl-CoA. For example. Micrococcus lysodeikticus is rich in 15C acids of both the iso type, 13-methyl-Ci4 or the anteiso type, 12-methyl-Ci4. These have been shown to originate from leucine and isoleucine respectively (Figure 3.8). 

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