Fatty acids chain reduction

Fatty acids derived from animal and vegetable sources generally contain an even number of carbon atoms siace they are biochemically derived by condensation of two carbon units through acetyl or malonyl coenzyme A. However, odd-numbered and branched fatty acid chains are observed ia small concentrations ia natural triglycerides, particularly mminant animal fats through propionyl and methylmalonyl coenzyme respectively. The glycerol backbone is derived by biospeciftc reduction of dihydroxyacetone. 

Fatty acid chains are taken apart two carbon atoms at a time by (3 oxidation. Biosynthesis of fatty acids reverses this process by using the two-carbon acetyl unit of acetyl-CoA as a starting material. The coupling of ATP cleavage to this process by a carboxylation-decarboxylation sequence, the role of acyl carrier protein (Section H,4), and the use of NADPH as a reductant (Section I) have been discussed and are summarized in Fig. 17-12, which gives the complete sequence of... 

For fatty acid biosynthesis, reduction after each condensation step affords a growing hydrocarbon chain. In the absence of this reduction process, the growing poly- -keto chain needs to be stabilized on the enzyme surface until the chain length is complete, at which point cyclization or other reactions can occur. The poly-fj-kelo ester is very reactive, and there are various possibilities... 

In insects, especially Diptera, several pioneer studies reviewed by Blomquist et al. (1987) established that long chain hydrocarbons, some of which play a pheromone role, were derived from very long chain fatty acids by reduction and decarboxylation. Thus, pheromone biosynthesis shares steps with those leading to basic lipid molecules and also with those of the well-known pheromones of Lepidoptera (Roelofs and Wolf, 1988). All often display several double bonds located in various positions while the volatile butterfly compounds bear functional groups (acetate, aldehyde or alcohol) and aliphatic chains with 12-16 carbons. Contact pheromones of flies have much longer chains (21C-39C) (Pennanec h et al., 1991). 

A process with potential practical applicability is the hydrogenation of edible oils. Reduction of multiply unsaturated triglycerides with hydrogen over Ni-based catalysts is frequently used to gain autoxidative stability of edible oils. According to the Polanyi-Horiuti mechanism, multiple 1,2 or 1,4 diadsorption of the fatty acid tail with exclusively c/s-configuration around the double bonds causes cis-trans isomerisation, whilst the number of double bonds is being reduced. The trans-fatty acid chains have adverse effects on the human metabolism and must be minimized. 

In the second round of fatty acid synthesis, butyryl ACP condenses with malonyl ACP to form a C5-P-ketoacyl ACP. This reaction is like the one in the first round, in which acetyl ACP condenses with malonyl ACP to form a C4-P-ketoacyl ACP. Reduction, dehydration, and a second reduction convert the C5-P-ketoacyl ACP into a C5-acyl ACP, which is ready for a third round of elongation. The elongation cycles continue until Ci5-acyl ACP is formed. This intermediate is a good substrate for a thioesterase that hydrolyzes C 15-acyl ACP to yield palmitate and ACP. The thioesterase acts as a ruler to determine fatty acid chain length. The synthesis of longer-chain fatty acids is discussed in Section 22.6. 

ER fatty acid chain elongation, which uses two-carbon units provided by mal-onyl-CoA, is a cycle of condensation, reduction, dehydration, and reduction reactions similar to those observed in cytoplasmic fatty acid synthesis. In contrast to the cytoplasmic process, the intermediates in the ER elongation process are CoA esters. These reactions can lengthen both saturated and unsaturated fatty acids. Reducing equivalents are provided by NADPH. 

Fatty acids. Selective reduction in short-chain fatty acids (C < 20) and input of long-chain fatty acids (C > 20) in deeper layers suggest an alteration with time. The 12, 16, and 18 fatty acids as detected in the seafloor surface samples, would reflect original composition of OM and indicate a marine origin of the slope sediments. 

The malonic ester synthesis might seem like an arcane technique that only an organic chemist would use. Still, it is much like the method that cells use to synthesize the long-chain fatty acids found in fats, oils, waxes, and cell membranes. Figure 22-4 outlines the steps that take place in the lengthening of a fatty acid chain by two carbon atoms at a time. The growing acid derivative (acyl-CoA) is activated as its thioester with coenzyme A (structure on page 1027). A malonic ester acylation adds two of the three carbons of malonic acid (as malonyl-CoA), with the third carbon lost in the decarboxylation. A )8-ketoester results. Reduction of the ketone, followed by dehydration and reduction of... 

Branch methyl groups located near the center of the fatty acid chain are derived by carbon transfer firom 5-adenosyl-L-methionine to an unsaturated fatty acyl derivative in a phospholipid, followed by a reduction, e.g. synthesis of lO-methyktearic acid (tuber-culostearic add) in mycobacteria, Nocardia, Sirepio-myces and Brevibacterium ... 

The ketoacyl-ACP is then reduced to yield a hydroxyl group. In turn, this is dehydrated to yield a carbon-carbon double bond, which is reduced to yield a saturated fatty acid chain. Thus, the sequence of chemical reactions is the reverse of that in P-oxidation (section 5.5.2). For both reduction reactions in fatty acid synthesis, NADPH is the hydrogen donor. One source of this NADPH is the pentose phosphate pathway (section 5.4.2) and the other is the oxidation of malate (arising from oxaloacetate) to pyruvate, catalysed by the malic enzyme (see Figure 5.27). 

Allenic groups have distinctive IR and NMR spectra, and all the natural fatty acids containing this functional group exhibit a marked optical activity. The position of the group in the fatty acid chain can be determined by partial reduction and oxidation of the monoene fragments as described above [74]. 

As fatty acids or triacylglycerols cool, Gibbs free energy (G = H — TS) decreases by reduction of both enthalpy (H) and entropy (5, the degree of disorder). At decreased S, the fatty acid chains assume polelike structures... 

If a two-carbon unit is added to an already existing chain containing 2 or more carbons in order to obtain fatty acids, two reductions are necessary, each of which requires 2 electrons. 

D Adamo et al. (1961) have studied the distribution of hydrogen of lactate-2- H in the fatty acid chain. Only 3% of radioactivity were found in the terminal methyl group, and, as almost no isotopes were recovered in the a position, reduction mechanisms, probably via NADH, were involved in hydrogen incorporation. 

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