Acyl carrier protein derivatives

This enzyme [EC 2.3.1.15] catalyzes the reaction of an acyl-CoA with xn-glycerol 3-phosphate to produce coenzyme A and a l-acyl-xn-glycerol 3-phosphate. The acyl-CoA derivatives contain an acyl group with a chain length of at least ten carbon atoms. In addition, the acyl-CoA can be substituted by an acyl-[acyl-carrier protein] derivative. 

This enzyme, officially known as 3-hydroxypalmitoyl-[acyl-carrier protein] dehydratase [EC 4.2.1.61], is the fatty-acid synthase component that catalyzes the conversion of (3 i )-3-hydroxypalmitoyl-[acyl-carrier protein] to form 2-hexadecenoyl-[acyl-carrier protein] and water. This enzyme displays specificity toward 3-hydroxyacyl-[acyl-carrier protein] derivatives (with chain lengths from Ci2 to Cie), with highest activity on the palmitoyl derivative. See also Fatty Acid Synthetase... 

This enzyme [EC 1.1.1.100], also known as 3-oxoacyl-[acyl-carrier protein] reductase, catalyzes the reaction of a (3i )-3-hydroxyacyl-[acyl-carrier protein] with NADP to produce 3-oxoacyl-[acyl-carrier protein] and NADPH. The enzyme prefers acyl-carrier protein derivatives over simple CoA derivatives as substrates. 

Acyl carrier protein, fatty acid synthase sequence, 45-46 Acyl carrier protein derivatives, desaturation, 13,l4f Acyl lipids, formation, 47-48 Aglycone skeletons saponins, 288f Solanum glycoalkaloids, 288f... 

Fatty add synthase is a large multienzyme complex in the cytoplasm that is rapidly induced in the liver after a meal by high carbohydrate and the concomitant rise in insulin levels. It contains an acyl carrier protein (AGP) that requires the vitamin pantothenic add. Althoi malonyl CoA is the substrate used by fetty acid synthase, only the carbons from the acetyl CoA portion are actually incorporated into the fatty acid produced. Therefore, the fetty add is derived entirely from acetyl CoA. 

This enzyme catalyzes the reaction of an acyl-CoA derivative with l-acyl-vn-glycerol 3-phosphate to generate coenzyme A and l,2-diacyl-5 n-glycerol 3-phosphate. The animal enzyme is reported to be specific for the transfer of unsaturated fatty acyl groups. Interestingly, the acyl-[acyl-carrier-protein] can also act as an acyl donor. 

V2 2 Second derivative operator, + 02 ACP Acyl carrier protein... 

The remaining series of reactions of fatty acid synthesis in eukary-l otes is catalyzed by the multifunctional, dimeric enzyme, fatty acid synthase. Each fatty acid synthase monomer is a multicatalytic polypeptide with seven different enzymic activities plus a domain that covalently binds a molecule of 4 -phosphopantetheine. [Note 4-Phosphopantetheine, a derivative of the vitamin pantothenic add (see p. 379), carries acetyl and acyl units on its terminal thiol (-SH)j group during fatty acid synthesis. It also is a component of 00-enzyme A.] In prokaryotes, fatty acid synthase is a multienzyme complex, and the 4 -phosphopantetheine domain is a separate protein, referred to as the acyl carrier protein (ACP). ACP is used below to refer to the phosphopantetheine-binding domain of the eukaryotic fatty acid synthase molecule. The reaction numbers in1 brackets below refer to Figure 16.9. [Note The enzyme activities listed are actually separate catalytic domains present in each mulf-1 catalytic fatty acid synthase monomer.]... 

A closely related E. coli protein is a 79-kDa multifunctional enzyme that catalyzes four different reactions of fatty acid oxidation (Chapter 17). The amino-terminal region contains the enoyl hydratase activity.32 A quite different enzyme catalyzes dehydration of thioesters of (3-hydroxyacids such as 3-hydroxydecanoyl-acyl carrier protein (see Eq. 21-2) to both form and isomerize enoyl-ACP derivatives during synthesis of unsaturated fatty acids by E. coli. Again, a glutamate side chain is the catalytic base but an imidazole group of histidine has also been implicated.33 This enzyme is inhibited irreversibly by the N-acetylcysteamine thioester of 3-decynoic acids (Eq. 13-8). This was one of the first enzyme-activated inhibitors to be studied.34... 

Branched carbon skeletons are formed by standard reaction types but sometimes with addition of rearrangement steps. Compare the biosynthetic routes to three different branched five-carbon units (Fig. 17-19) The first is the use of a propionyl group to initiate formation of a branched-chain fatty acid. Propionyl-CoA is carboxylated to methylmalonyl-CoA, whose acyl group is transferred to the acyl carrier protein before condensation. Decarboxylation and reduction yields an acyl-CoA derivative with a methyl group in the 3-position. 

Figure 21-3 Major pathways of synthesis of fatty acids and glycerolipids in the green plant Arabidopsis. The major site of fatty acid synthesis is chloroplasts. Most is exported to the cytosol as oleic acid (18 1). After conversion to its coenzyme A derivative it is converted to phosphatidic acid (PA), diacylglycerol (DAG), and the phospholipids phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Desaturation also occurs, and some linoleic and linolenic acids are returned to the chloroplasts. See text also. From Sommerville and Browse.106 See also Figs. 21-4 and 21-5. Other abbreviations monogalactosyldiacylglycerol (MGD), digalactosyldiacylglycerol (DGD), sulfolipid (SL), glycerol 3-phosphate (G3P), lysophosphatidic acid (LPA), acyl carrier protein (ACP), cytidine diphosphate-DAG (CDP-DAG).

Outline of the reactions for fatty acid biosynthesis. Fatty acids grow in steps of two-carbon units and take place on a multienzyme complex, (a) The initial reactions of fatty acid biosynthesis are shown. In the first reaction, acetyl-CoA reacts with ACP (acyl carrier protein) to form acetyl-ACP (step 1). ACP is shown with its SH group emphasized (see fig. 18.13) to remind readers that the acyl derivatives are linked to ACP via a thioester bond. Malonyl-CoA, derived from the carboxylation of acetyl-CoA (see fig. 18.9), reacts... 

FIGURE 19.4 Modular organization of the six modules (I—VI) of 6-deoxyerythronolide B synthase (DEBS) enzyme as derived from Saccharopolyspora erythraea. Enzyme activities are acyltransferases (AT), acyl carrier proteins (ACP), fi-ketoacyl-ACP synthases (KS), P-ketoreductases (KR), dehytratases (DH), enoyl reductases (ER), and thioesterases (TE). The TE-catalyzed release of the polyketide chain results in the formation of 6-dEB (70), 375 379 383... 

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 ... 

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. 

Organisms of all biological kingdoms convert 64 into the cys-teamine derivative phosphopantetheine (65) using L-cysteine as substrate. 65 is converted to coenzyme A (66) by attachment of an adenosine moiety via a pyrophosphate linker and phosphorylation of the ribose moiety. Phosphopantetheine can be attached covalently to serine residues of acyl carrier proteins that are parts of fatty acid synthases and polyketide synthases. 

In plant systems, de novo synthesis occurs in the plastid and results mainly in the conversion of acetate to palmitate. All 16 carbon atoms in palmitic acid are derived from acetate— half from the methyl carbon and half from the acyl carbon. Two of the carbon atoms (C-15 and C-16) come directly from acetate, and the other 14 come from acetate via the more reactive malonate. Production of malonate requires the incorporation of an additional carbon atom into the acetyl group. This is supplied as bicarbonate, and this same carbon atom is subsequently lost as carbon dioxide. The acyl groups are attached to co-enzyme A (CoASH) during part of the cycle and to acyl carrier protein (ACPSH) during another part. The abbreviated symbols used for these co-enzymes emphasize the thiol groups (SH) to which the acyl chains are attached. 

Pantothenic acid is of ubiquitous occurrence in nature, where it is synthesized by most microorganisms and plants fi-om pantoic acid (D-2,4-dihydroxy-3,3-dimethylbutyric acid) derived from L-vafine, and p-alanine derived from L-aspartate. Addition of cysteamine at the C-terminal end and phosphorylation at C4 of pantoic acid forms 4 -phosphopantetheine, which serves as a covalently attached prosthetic group of acyl carrier proteins, and, when attached... 

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