Acyl carrier protein, function

Acyl azide, amines from, 935 Acyl carrier protein, function of, 1 140 Acyl cation, electrostatic potential map of, 558... 

In bacteria and plants, the individual enzymes of the fatty acid synthase system are separate, and the acyl radicals are found in combination with a protein called the acyl carrier protein (ACP). However, in yeast, mammals, and birds, the synthase system is a multienzyme polypeptide complex that incorporates ACP, which takes over the role of CoA. It contains the vitamin pantothenic acid in the form of 4 -phosphopan-tetheine (Figure 45-18). The use of one multienzyme functional unit has the advantages of achieving the effect of compartmentalization of the process within the cell without the erection of permeability barriers, and synthesis of all enzymes in the complex is coordinated since it is encoded by a single gene. 

Figure 21-2. Fatty acid synthase multienzyme complex. The complex is a dimer of two identical polypeptide monomers, 1 and 2, each consisting of seven enzyme activities and the acyl carrier protein (ACP). (Cys— SH, cysteine thiol.) The— SH of the 4 -phosphopantetheine of one monomer is in close proximity to the— SH of the cysteine residue of the ketoacyl synthase of the other monomer, suggesting a "head-to-tail" arrangement of the two monomers. Though each monomer contains all the partial activities of the reaction sequence, the actual functional unit consists of one-half of one monomer interacting with the complementary half of the other. Thus, two acyl chains are produced simultaneously. The sequence of the enzymes in each monomer is based on Wakil.

Pantothenic acid Functional part of CoA and acyl carrier protein fatty acid synthesis and metabolism ... 

Pantothenic acid has a central role in acyl group metabolism when acting as the pantetheine functional moiety of coenzyme A or acyl carrier protein (ACP) (Figure 45-18). The pantetheine moiety is formed after combination of pantothenate with cysteine, which provides... 

Kato, Y., Bai, L., Xue, Q. et al. (2002) Functional expression of genes involved in the biosynthesis of the novel polyketide chain extension unit, methoxymalonyl-acyl carrier protein, and engineered biosynthesis of 2-desmethyl-2-methoxy-6-deoxyerythronolide B. Journal of the American Chemical Society, 124, 5268. 

Each subunit of the enzyme binds acetyl residues as thioesters at two different SH groups at one peripheral cysteine residue (CysSH) and one central 4-phosphopante-theine group (Pan-SH). Pan-SH, which is very similar to coenzyme A (see p. 12), is covalently bound to a protein segment of the synthase known as the acyl-carrier protein (ACP). This part functions like a long arm that passes the substrate from one reaction center to the next. The two subunits of fatty acid synthase cooperate in this process the enzyme is therefore only capable of functioning as a dimer. 

Synthesis of fatty acids in bacteria requires a small acyl carrier protein (ACP) whose functions are similar to those of CoA. However, it contains pante-... 

Both bacteria and plants have separate enzymes that catalyze the individual steps in the biosynthetic sequence (Fig. 17-12). The fatty acyl group grows while attached to the small acyl carrier protein (ACP).54 58 Control of the process is provided, in part, by the existence of isoenzyme forms. For example, in E. coli there are three different P-oxoacyl-ACP synthases. They carry out the transfer of any acyl primer from ACP to the enzyme, decarboxylate malonyl-ACP, and carry out the Claisen condensation (steps b, e, and/in Eq. 17-12)58a e One of the isoenzymes is specialized for the initial elongation of acetyl-ACP and also provides feedback regulation.58c The other two function specifically in synthesis of unsaturated fatty acids. 

Citrate lyase catalyzes the cleavage of citrate to oxaloacetate and acetate in the presence of Mg2+ or Mn2+, but in the presence of EDTA it catalyzes its synthesis. The enzyme is a complex of three subunits. The y-subunit functions as an acyl carrier protein (ACP). The a-subunit is an acyl transferase involved in citryl-ACP formation and the release of acetate, and the /8-subunit catalyzes the cleavage of the citryl-ACP intermediate to oxaloacetate and acetyl-ACP. The enzyme from Klebsiella aerogenes has been purified, and binds 18 Mn2"1 in a cooperative manner. 

The last step in the fatty acid biosynthetic pathway is catalyzed by enoyl-acyl carrier protein (ACP) reductase, which is responsible for reduction of the double bond in the enoyl-ACP derivative (Heath and Rock, 1995 Payne et al., 2002). While fabl genes encode enoyl-ACP reductases (FabI enzymes) in S. aureus and E. coli, an alternative enoyl-ACP reductase, FabK, replaces the function of Fabl in a number of bacterial species such as Streptococcus pneumoniae (Heath and Rock, 2000). More interestingly, a number of bacterial species (such as Enterococcus faecalis and Pseudomonas aeruginosa) possess both the Fabl and FabK enzymes (Heath and Rock, 2000). To discover Fabl-specific antibacterial inhibitors, Payne and colleagues at GlaxoSmithKline (GSK) developed assays for various versions of enoyl-ACP reductases (Payne et al., 2002 Seefeld et al., 2003) based on the following reaction scheme ... 

The )9-ketoacyl-synthases/acyltransferases (KS/ AT) in each module effect the chain elongation by methyl-malonyl-coenzyme A units catalyzing a Claisen e.ster condensation followed by decarboxylation (Scheme 2). Subsequent domains are module-specific ketoreductases (KR), dehydratases (DH) or enoyl-reductases (ER), which regulate the functionalization of the newly prepared fi-oxoesters. The stepwise growing chain is picked up by an acyl-carrier protein (ACP). 

Pantothenic acid has a central role in energy-yielding metabolism as the functional moiety of coenzyme A (CoA), in the biosynthesis of fatty acids as the prosthetic group of acyl carrier protein, and through its role in CoA in the mitochondrial elongation of fatty acids the biosynthesis of steroids, porphyrins, and acetylcholine and other acyl transfer reactions, including postsynthetic acylation of proteins. Perhaps 4% of all known enzymes utilize CoA derivatives. CoA is also bound by disulfide links to protein cysteine residues in sporulating bacteria, where it may be involved with heat resistance of the spores, and in mitochondrial proteins, where it seems to be involved in the assembly of active cytochrome c oxidase and ATP synthetase complexes. 

Vagelos PR, Majerus PW, Alberts AW, Larrahee AR, Ailhaud CP. Structme and function of the acyl carrier protein. Eed. Proc. 1966 25 1485-1494. 

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