Transacylase, transacylation

Knudsen and Grunnet (1982) have proposed an interesting system for the control of medium-chain fatty acid synthesis by ruminant mammary tissue. Their proposal is based on their observations that ruminant mammary tissue fatty acid-synthetase exhibits both medium-chain thioesterase (Grunnet and Knudsen 1978) and transacylase (Knudsen and Grunnet 1980) activity and that medium-chain fatty acids synthesized de novo can be incorporated into TG without an intermediate activation step (Grunnet and Knudsen 1981). They proposed that the synthesis of the medium-chain fatty acids is controlled by their incorporation into TG (Grunnet and Knudsen 1981). Further work will be needed to substantiate transacylation as a chain-termination mechanism in fatty acid synthesis by ruminant mammary tissue. 

Elegant experiments, which capitalized on the ability of iodoacetamide to specifically alkylate the active site cysteine of the -ketoacyl synthase, were performed, which definitively proved the capability of the yeast FAS in decar-boxylating malonyl CoA [75]. Following alkylation, FAS activity is abolished however, the enzyme still transacylates malonyl CoA to the phosphopantetheine thiol, where it is decarboxylated before being transferred back to CoA by the transacylase prior to its release as acetyl CoA. 

Kumar, P., Koppisch, A.T., Gane, D.E. Khosla, G. Enhancing the modularity of the modular polyketide synthases transacylation in modular polyketide synthases catalyzed by malonyl-GoA AGP transacylase. J. Am. Chem. Soc. 125, 14307-14312 (2003). 

Fig. 9. Biosynthesis of platelet-activating factor (PAF) via the remodeling pathway. Lyso-PAF, the immediate precursor of PAF, can be formed from l-alkyl-2-acyl-sn-glycero-3-phosphocholine through the direct action of (I) PLAj or (II) CoA-independent transacylase. The lysoplasmenylethanolamine (or other potential ethanolamine- and choline-containing lysoglycerophospholipids) is thought to be generated by (III) a PLAj that exhibits a high degree of selectivity for substrates with an atachidonoyl moiety at the sn-2 position. The transacylase (II) appears to possess both acyl transfer and PLAj hydrolytic activities. Lyso-PAF produced by either the transacylation (II) or direct PLAj (I) action can be acetylated to form PAF by (IV) an acetyl-CoA acetyltransferase.

Transacylation reversible transfer of acyl groups (R-CO-) from a donor to an acceptor, e.g. transfer of the acyl residue CH3-CO- from acetyl-CoA to an acceptor Y CH3-CO - S-CoA -t Y -> CH3-CO-Y + CoA. T. is catalysed by transacylases, which are important in the synthesis and degradation of fatty acids, synthesis of conjugated bile acids via cholic acid-CoA compounds, and other reactions such as acetylation of amino acids and amines. 

In animals and microorganisms, NAPE appeared to be synthesized by a Ca " -dependent transacylase activity whereby a fatty acid is transferred from the 5 -lor -2 0-acyl position of a phospholipid to the ethanolamine head group of PE (Schmid et al., 1990). Evidence indicated that transacylation could occur intermolecularly (with PE, PC or cardiolipin able to serve as the acyl donor), or intramolecularly. Most notably, free fatty acids or acyl moieties from fatty acylCoA were not incorporated into NAPE. To date, this transacylase activity has not been solubilized from any membrane source in an active form. 

It is well known that the two-carbon units for condensation in de novo fatty acid synthesis are provided as malonate. A specific transacylase transfers the malonate from coenzyme A to ACP. Malonyl-CoA ACP transacyl-ases have been purified from a number of sources including leaf and seed tissues as well as the cyanobacterium Anabaena variabilis. The enzymes usually have masses of about 40 kDa and appear to use a random sequence mechanism. Tissue-specific isoforms have been reported in some instances though their significance is not known. 

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