Fatty acid elongase system

This pathway (the microsomal system ) elongates saturated and unsaturated fatty acyl-CoAs (from Cjg upward) by two carbons, using malonyl-CoA as acetyl donor and NADPH as reductant, and is catalyzed by the microsomal fatty acid elongase system of enzymes (Figure 21-5). Elongation of stearyl-CoA in brain increases rapidly during myehnation in order to provide C22 and C24 fatty acids for sphingoEpids. 

The rate limiting step in fatty acid synthesis is catalyzed by acetyl-CoA carboxylase to produce malonyl-CoA at the expense of one ATP.31 Malonate and acetate are transferred from CoA to acyl carrier protein in the cytosolic fatty acid synthetase complex, where chain extension leads to the production of palmitate. Palmitate can then be transferred back to CoA, and the chain can be extended two carbons at a time through the action of a fatty acid elongase system located in the endoplasmic reticulum. The >-hydroxylation that produces the >-hydroxyacids of the acylceramides is thought to be mediated by a cytochrome p450 just when the fatty acid is long enough to span the endoplasmic reticular membrane. 

Figure 21-S. Microsomal elongase system for fatty acid chain elongation. NADH is also used by the reductases, but NADPH is preferred.

SYNTHESIS OF POLYUNSATURATED FATTY ACIDS INVOLVES DESATURASE ELONGASE ENZYME SYSTEMS... 

Figure 23-3. Biosynthesis of the co9, co6,and co3 families of polyunsaturated fatty acids. Each step is catalyzed by the microsomal chain elongation or desaturase system 1,elongase 2,A desaturase 3,A desaturase 4,A desaturase. ( .Inhibition.)...

Increasing the degree of unsaturation and chain length of these fatty acids is achieved by enzymes known as desaturases and elongases (Sinnhuber et al., 1972). Their activity is greatly influenced by temperature, as we have seen earlier under temperature compensation , even in isolated systems. Schiinke and Wodtke (1983) observed a 30-fold increase in the desaturase activity of the... 

The end product of the Type II fatty acid synthetase of plants is palmitoyl-ACP (Stumpf, 1980) which then serves as the substrate for the elongation system (palmitate elongase). Palmitate elongase has been studied in a number of soluble and membrane-bound subcellular fractions from plants (cf. Harwood, 1979). The enzyme is sensitive to arsenite in contrast to the Type II synthetase which is inhibited by cerulenin. These selective inhibitions seem to be related to the properties of the )8-ketoacyl-ACP synthetase. Two of these enzymes have been purified from spinach leaves (Shimakata and Stumpf, 19826). One will condense a broad range of primer units (up to C14) and is sensitive to cerulenin whereas the second is specific for palmitoyl-ACP and is inhibited by arsenite. The latter enzyme can, therefore, be regarded as a key part of the Type III synthetase, palmitate elongase. 

It was shown years, ago that C20-C24 fatty acids are chiefly located in the plasma membrane of leek cells, but are synthesized in (by) the endomembrane system. Two acyl-CoA elongases were detected, one elongating ClS-CoA chiefly in the ER, the second elongating C20-CoA chiefly in the GA. The elongases were solubilized and partially purified. The kinetic parameters have been studied and the role of the surrounding membrane lipids on the C20-C24 fatty acid biosynthesis is being investigated (see also LESSIRE et al., this volume BESSOULE et al., this volume). 

Fatty acid synthetases can be divided mainly into Type I and Type II enzymes (Table 3.8). Type I synthetases are multifunctional proteins in which the proteins catalysing the individual partial reactions are discrete domains. This type includes the animal synthetases and those from higher bacteria and yeast. Type II synthetases contain enzymes which can be separated, purified and studied individually. This system occurs in lower bacteria and plants and has been studied most extensively in E. coli. In addition, Type III synthetases - occurring in different organisms - catalyse the addition of C2 units to preformed acyl chains and are also known as elongases. Although, historically, the reactions of the yeast synthetase were unravelled first, we shall start by describing the separate reactions catalysed by the enzymes of E. coli. 

Very long chain fatty acids in plants are made by membrane-bound enzyme systems utilizing malonyl-CoA as the source of 2C units in similar fashion to the animal elongases. Acyl-CoAs have been shown to be the substrates in some of these systems and various elongases have been demonstrated which have different chain-length specificities. The production of very long chain (> 18C) fatty acids is required for the formation of the surface-covering layers, cutin and suberin (section 6.6.1), as well as for seed oil production in commercially-important crops such as rape and jojoba (sections 4.3 and 4.7). 

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