Acyl CoA elongation systems

Vaz A. H., Jurenka R. A., Blomquist G. J. and Reitz R. C. (1988) Tissue and chain length specificity of the fatty acyl-CoA elongation system in the American cockroach. Arch. Biochem. Biophys. 267, 551-557. 

In studies with extracts of jojoba cotyledons, Pollard et al. (1979) clearly showed that the acyl-CoA elongation system which converted oleoyl-CoA to... 

Acyl-CoA Elongation Systems in Allium porrum Microsomes. 525... 

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. 

Although less active than the microsomal system, mitochondrial chain elongation has been extensively investigated, particularly in liver and brain. The two-carbon elongation donor in mitochondria is acetyl-CoA. Generally, a monounsaturated fatty acyl-CoA substrate is more active than saturated CoA and both support higher activity than PUFA, particularly in brain. 

Elongation of the acyl group to make fatty acids longer than 16 carbons (palmitate) occurs apart from palmitate synthesis. Whereas palmitate synthesis occurs in the cytosol, elongation occurs in both the mitochondria and endoplasmic reticulum (ER). The ER is the dominant system. Elongation in the ER differs from cytosolic synthesis in employing coenzyme A (instead of acyl carrier protein) and separate enzymes (instead of a complex). The condensation reaction occurs between malonyl-CoA and an acyl-CoA to form a / -ketoacyl-CoA (see here and here). Two enzymes catalyze this step in the endoplasmic reticulum, one of which is specific for unsaturated fatty acyl-CoAs. 

A mitochondrial system for elongation of fatty acid chains, using acetyl-CoA as the two-carbon donor does exist but has limited activity with acyl-CoA substrates with 16 or more carbon atoms and is probably concerned with the lengthening of shorter chains. 

The acyl-CoA synthesis is faster than elongation or desaturation reactions (Marcel and Suzue, 1972). The enz3nnes involved in the elongation are found either in the endoplasmic reticulum or in mitochondria but the specificity of each group is different. The microsomal system prefers A6 unsaturated acyl-CoA and hexanoyl CoA whereas the mitochondrial prefers medium chain acyl-CoA (Podack et al, 1974 Hinsch and Seubert, 1975). 

Elongating systems in mitochondria. Brain mitochondria are able to elongate acyl-CoA in the presence of acetyl-CoA (16). Pal-mityl-CoA is elongated by acetyl-CoA in the presence of NADPH and NADH providing mainly stearic acid. Similar patterns for enzymatic activity, cofactors, optimal pH and substrate requirements are found for stearyl-CoA elongation presuming that the same enzyme systems elongate both acyl-CoA (contrary to microsomes) (17). 

The mitochondrial system in the liver is active in the elongation of acyl-CoA derivatives with acetyl-CoA in the presence of NADH and NADPH. The intermediates and enz3nnes are similar to those of the mitochondrial 3-oxidation system but the apparent rate-limiting reaction, NADPH enoyl-CoA reductase, is distinctive (Hinsch Seubert, 1975). 

Further desaturation and acyl chain elongation of fatty acids are generally accepted to involve cytosolic membranous systems associated with the endoplasmic reticulum (Stumpf, 1989). A critical importance, therefore, would appear to exist for a detailed understanding of the mechanics by which the fatty acids are exported from the plastid. At present, there is little available information on the precise transport system or its regulation. Although fatty acids are presumed to be released on hydrolysis of acyl-ACPs by specific thioesterases, it is not known whether an initial formation of acyl-CoA is required prior to transport across the plastidic membrane in association with carnitine or some other system. A direct transacylation between ACP and CoA or some carrier system would be less expensive energetically than a process involving hydrolysis and synthesis. 

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