Branched-chain fatty acid biosynthesis

Although the mitochondria are the primary site of oxidation for dietary and storage fats, the peroxisomal oxidation pathway is responsible for the oxidation of very long-chain fatty acids, jS-methyl branched fatty acids, and bile acid precursors. The peroxisomal pathway also plays a role in the oxidation of dicarboxylic acids. In addition, it plays a role in isoprenoid biosynthesis and amino acid metabolism. Peroxisomes are also involved in bile acid biosynthesis, a part of plasmalogen synthesis and glyoxylate transamination. Furthermore, the literature indicates that peroxisomes participate in cholesterol biosynthesis, hydrogen peroxide-based cellular respiration, purine, fatty acid, long-chain... 

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]. 

Familial adenomatous polyposis 574 Faraday, numerical value of 283 Farnesyl group 402, 559 Fat(s). See also Triacylglycerol (triglyceride) composition of 380 hydrolysis of 507 Fatty acid(s) 380-382 activation of 512 acyl CoA, derivatives of 507 biosynthesis of 722 branched chain 381 cyclopropane-containing 399 essential 721 in lipids 380 names of, table 380 oxidation 511 pKa values of 380 stability of 589... 

Kaneda, T., Biosynthesis of Branched-Chain Fatty Acids. V. Microbial... 

The biosynthesis of terpenes clearly follows a somewhat different course from fatty acids in that branched-chain compounds are formed. One way that this can come about is for 2-oxobutanoyl coenzyme A to undergo an aldol addition at the keto carbonyl group with the ethanoyl coenzyme A to give the 3-methyl-3-hydroxypentanedioic acid derivative, 8 ... 

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]. 

These results confirmed that branched-chain amino acid catabolism via the BCDH reaction provides the fatty acid precursors for natural avermectin biosynthesis in S. avermitilis. In contrast, B. subtilis appears to possess two mechanisms for branched-chain precursor supply. The dual substrate pyruvate/branched-chain a-keto acid dehydrogenase (aceA) and an a-keto acid dehydrogenase (bfmB), which also has some ability to metabolize pyruvate, appears to be primarily involved in supplying the branched-chain initiators of long, branched-chain fatty acid biosynthesis [32,42], Two mutations are therefore required to generate the bkd phenotype in B. subtilis [31,42],... 

Figure 6.7 Biosynthesis of (2 ,4 ,6 )-5-ethyl-3-methyl-2,4,6-nonatriene, pheromone component of Carpophilus freemani Dobson (Nitidulidae). The pathway is a modification of normal fatty acid biosynthesis, involving initiation with acetate elongation with first propionate (to provide the methyl branch), then butyrate (to provide the ethyl branch) and chain termination with a second butyrate. The final butyrate to add suffers a loss of C02, after adding in a unique head-to-head reaction. Intermediates of the pathway likely occur as activated (e.g. CoA) derivatives (Petroski et al., 1994 Bartelt and Weisleder, 1996).

Several pheromones may be involved in mediating the mating behavior of the yellow mealworm, Tenebrio molitor L. (reviewed in Plarre and Vanderwel, 1999), but only one has been identified to date. Tanaka et al. (1986, 1989) identified the female-produced male attractantas(4/ )-(+)-4-methylnonan-l-ol(4-methylnonanol). Females produce the pheromone through a modification of normal fatty acid biosynthesis (Islam et al., 1999 Bacala, 2000). Initiation of the pathway with one unit of propionate results in the uneven number of carbons in the chain incorporation of another unit of propionate during elongation provides the methyl branch reduction of the fatty acyl intermediate produces the alcohol pheromone (Figure 6.8). 

Methyl-branched fatty acids are intermediates in branched alkane biosynthesis (Juarez et al., 1992). Thus, [l-14C]propionate labeled methyl-branched fatty acids of 16-20 carbons, but did not label straight chain-saturated and monounsaturated fatty acids (Chase et al., 1990). 

The biosynthesis of hydrocarbons occurs by the microsomal elongation of straight chain, methyl-branched and unsaturated fatty acids to produce very long-chain fatty acyl-CoAs (Figure 11.1). The very long chain fatty acids are then reduced to aldehydes and converted to hydrocarbon by loss of the carboxyl carbon. The mechanism of hydrocarbon formation has been controversial. Kolattukudy and coworkers have reported that for a plant, an algae, a vertebrate and an insect, the aliphatic aldehyde is decarbonylated to the hydrocarbon and carbon monoxide, and that this process does not require cofactors (Cheesbrough and Kolattukudy, 1984 1988 Dennis and Kolattukudy, 1991,1992 Yoder et al., 1992). In contrast, the Blomquist laboratory has presented evidence that the aldehyde is converted to hydrocarbon and carbon dioxide in a process that... 

Vitamin B12 is essential for the methylmalonyl-CoAmutase reaction. Methylmalonyl-CoA mutase is required during the degradation of odd-chain fatty acids and of branched-chain amino acids. Odd-chained fatty acids lead to propionyl-CoA as the last step of P-oxida-tion. Methylmalonyl-CoA can be derived from propionyl-CoA by a carboxylase reaction similar to that of fatty acid biosynthesis. The cofactor for this carboxylation reaction is biotin, just as for acetyl-CoA carboxylase. The reaction of methylmalonyl-CoA mutase uses a free radical intermediate to insert the methyl group into the dicar-boxylic acid chain. The product is succinyl-CoA, a Krebs cycle intermediate. The catabolisms of branched-chain lipids and of the branched-chain amino acids also require the methylmalonyl-CoA mutase, because these pathways also generate propionyl-CoA. 

Next to fumarate reduction, some organisms use specific reactions in lipid biosynthesis as an electron sink to maintain redox balance in anaerobically functioning mitochondria. In anaerobic mitochondria two variants are known the production of branched-chain fatty acids and the production of wax esters. The parasitic nematode Ascaris suum reduces fumarate in its anaerobic mitochondria, but instead of only producing acetate and succinate or propionate, like most other parasitic helminths, this organism also use the intermediates acetyl-CoA and propionyl-CoA to form branched-chain fatty acids (Komuniecki et al. 1989). This pathway is similar to reversal of P-oxidation and a complex mixture of the end products acetate, propionate, succinate and branched-chain fatty acids is excreted. In this pathway, the... 

Wongtangtintharn, S., Oku, H., Iwasaki, H., Toda, T. 2004. Effect of branched-chain fatty acids on fatty acid biosynthesis of human breast cancer cells. J. Nutr. Sci. Vitaminol. 50, 137-143. 

First, the use of two specific reactions — All desaturation and controlled 2 carbon chain shortening of fatty acid precursors to account for the biosynthesis of a large number of pheromones — has been an extremely fruitful approach. Even in a case where it seemed uncertain if this approach was appropriate (22)r it turned out that it was (23.). Other reactions should now be added to increase the range of products accounted for. Examples already mentioned include the A10 desaturase and the chain elongation of branched-chain starting materials. Other functional groups that appear in sex pheromones should also be accounted for, such as epoxides. 

Neurological complications also are associated with vitamin B-12 deficiency and result from a progressive demyelination of nerve cells. The demyelination is thought to result from the increase in methylmalonyl-CoA that result from vitamin B-12 deficiency. Methylmalonyl-CoA is a competitive inhibitor of malonyl-CoA in fatty acid biosynthesis as well as being able to substitute for malonyl-CoA in any fatty acid biosynthesis that may occur. Since the myelin sheath is in continual flux the methylmalonyl-CoA-induced inhibition of fatty acid synthesis results in the eventual destruction of the sheath. The incorporation methylmalonyl-CoA into fatty acid biosynthesis results in branched-chain fatty acids being produced that may severely alter the architecture of the normal membrane structure of nerve cells... 

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