Malonyl-CoA: acyl carrier protein

Malonyl-CoA Acyl carrier protein transacylase (MCAT or FabD) catalyzes the transfer of a malonyl group between coenzyme A and acyl carrier proteins that are the privileged transporters of the FASH system. Although essential, this enzyme is present in excess and does not have a regulatory role in the FASH pathway, which might explain the relative paucity of reported inhibitors [1],... 

SF Haydock, JF Aparicio, I Molnar, T Schwecke, LE Khaw, A Konig, AFA Marsden, IS Galloway, J Staunton, PF Leadlay. Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA acyl carrier protein trans-acylase domains in modular polyketide synthases. FEBS Lett 374 246-248, 1995. 

Fig. 2 Metabolic routes for mcl-PHA biosynthesis. Pseudomonas putida GPol synthesizes PHA through P-oxidation and P. putida KT2440 synthesizes PHA through fatty add de novo synthesis. Special PHA consisting of 4-hydroxyalkanoate, 5- hydroxyalkanoate, or 6-hydroxyalkanoate can be produced by various bacteria when suitable precursors are supplied. 1 acyl-CoA synthetase, 2 acyl-CoA dehydrogenase, 3 enoyl-CoA hydratase, 4 NAD-dependent (5)-3-hydroxyacyl-CoA dehydrogenase, 5 3-ketoacyl-CoA thiolase, 6 (ItFspecific enoyl-CoA hydratase, 7 NADPH-dependent 3-ketoacyl-CoA reducatase, 8 3-hydroxyacyl-CoA epimerase, 9 mcl-PHA polymerase, 10 acetyl-CoA carboxylase, 11 malonyl-CoA-acyl carrier protein (ACP) tiansacylase, 12 3-keto-ACP synthase, 13 3-keto-ACP reductase, 14 3-hydroxyacyl-ACP dehydratase, 15 enoyl-ACP reductase, 16 acyl-ACP thiolase, 17 (l )-3-hydroxyacyl-ACP-CoA transacylase, 18 mcl-PHA polymerase...

There is increasing evidence that in plant tissues the synthesis of palmitic acid, the most abundant and important saturated fatty acid in higher plants, involves at/e novo system, so called because it utilizes acetyl-CoA, malonyl-CoA, acyl carrier protein (ACP), and a battery of soluble, nonassociated enzymes (palmitoyl-ACP synthetase) to form, as its terminal product, palmi-toyl-ACP. Palmitoyl-ACP is then elongated by another set of enzymes called... 

Figure 7.7 Common metabolic pathways that are involved in the biosynthesis of PHA in microorganisms. FabC malonyl-CoA acyl carrier protein (ACP) transcylase, FabD malonyl-CoA-ACP transacylase, FabG 3-ketoacyl-CoA reductase, PhaA P-ketothiolase, PhaB NAOH-dependent acetoacetyl-CoA reductase, PhaC polyhydroxyalkanoates synthase, PhaG 3-hydroxyacyl-ACP GoA transferase, PhaJ (R)-enoyl-GoA hydratase and TCA tricarboxylic acid...

European Atomic Energy Community Ethylene-vinyl alcohol Malonyl-CoA acyl carrier protein Malonyl-CoA-ACP transacylase 3-Ketoacyl-CoA reductase... 

C. Oefner, H. Schulz, A. D Arcy, G.E. Dale, Mapping the active site of Escherichia coU malonyl-CoA-acyl carrier protein transacylase (FabD) by protein crystallography. Acta Crystallogr. Sect. D-Biol. Crystallogr. 62,613-618 (2006)... 

Stapleton, S.R. and Jaworskl, J.G. 1982. Malonyl-CoA acyl carrier protein transacylase from spinach. Fed.Proc., 41 1192. 

Malonyl-CoA is converted into malonyl-ACP (acyl-carrier protein) by a highly specific enzyme, ACP-malonyltransferase. Reactants participate in the synthetic pathway, only when linked to the ACP. Malonyl-ACP donates a two-carbon unit to elongate the acyl group attached to ACP. Initially, malonyl-ACP condenses with acetyl-ACP formed from acetyl-CoA by the action of ACP-acetyltrans-ferase. The enzyme is less specific than ACP-malo-nyltransferases and can also bond propionyl groups from propionyl-CoA to ACP to form pro-pionyl-ACP in the synthesis of fatty acids with an odd number of carbons. During the condensation reaction, CO2 is released to drive the formation of acetoacetyl-ACP, a reaction which otherwise would be thermodynamically unfavourable. The free energy provided by ATP in the carboxylation step is therefore employed to synthesize acetoacetyl-ACP from acetyl-ACP and malonyl-ACP. 

FIGURE 25.7 The pathway of palmhate synthesis from acetyl-CoA and malonyl-CoA. Acetyl and malonyl building blocks are introduced as acyl carrier protein conjugates. Decarboxylation drives the /3-ketoacyl-ACP synthase and results in the addition of two-carbon units to the growing chain. Concentrations of free fatty acids are extremely low in most cells, and newly synthesized fatty acids exist primarily as acyl-CoA esters. 

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. 

Figure 11.4 Condensation, dehydration and reduction reactions in fatty add synthesis. These reactions constitute the major components of the pathway of fatty acid synthesis and are all catalysed by fatty acid synthase. The reduction reactions, indicated by addition of 2H in the diagram, involve the conversion of NADPH to NADP . (The re-conversion of NADP back to NADPH occurs in the pentose phosphate pathway.) The condensation reaction results in an increase in size of acyl-ACP by two carbon units in each step. The two carbons for each extension are each provided by malonyl-CoA. ACP - acyl carrier protein.

This enzyme [EC 2.3.1.39], also known as acyl-carrier protein malonyltransferase, catalyzes the reaction of malonyl-CoA with an acyl-carrier-protein to produce coenzyme A and a malonyl-[acyl-carrier-protein]. 

MALONYL-CoA ACP-TRANSACYASE Acyl carrier protein synthase,... 

The sex pheromone is interesting from a biosynthetic perspective (see Fig. 4.3) because it is closely connected with primary metabohsm. That is, the monomer 4 is an intermediate in fatty acid biosynthesis. Condensation of acetyl-ACP (8 ACP, acyl carrier protein) with malonyl-CoA (9 CoA, coenzyme A) yields acetoacyl-ACP (10). Enantioselective reduction with NADPH leads to (R)-3-hydroxybutyryl-ACP (11). Two units of this precursor could then be condensed to form the pheromone 5, which then degrades to 4 and 6 as described above. Alternatively, 4 can also be formed by direct hydrolysis of intermediate 11. 

In non-ruminants, the malonyl CoA is combined with an acyl carrier protein (ACP) which is part of a six-enzyme complex (molecular weight c. 500 kDa) located in the cytoplasm. All subsequent steps in fatty acid synthesis occur attached to this complex through a series of steps and repeated cycles, the fatty acid is elongated by two carbon units per cycle (Figure 3.8, see also Lehninger, Nelson and Cox, 1993). 

Figure 3.8 One complete cycle and the first step in the next cycle of the events during the synthesis of fatty acids. ACP = acyl carrier protein, a complex of six enzymes i.e. acetyl CoA-ACP transacetylase (AT) malonyl CoA-ACP transferase (MT) /3-keto-ACP synthase (KS) /J-ketoacyl-ACP reductase (KR) / - hydroxyacyl-ACP-dehydrase (HD) enoyl-ACP reductase (ER).

The core of the E. coli fatty acid synthase system consists of seven separate polypeptides (Table 21-1), and at least three others act at some stage of the process. The proteins act together to catalyze the formation of fatty acids from acetyl-CoA and malonyl-CoA. Throughout the process, the intermediates remain covalently attached as thioesters to one of two thiol groups of the synthase complex. One point of attachment is the —SH group of a Cys residue in one of the seven synthase proteins (j3-ketoacyl-ACP synthase) the other is the —SH group of acyl carrier protein. 

After malonyl-CoA synthesis, the remaining steps in fatty acid synthesis occur on fatty acid synthase, which exists as a multienzyme complex. In the initial reactions acetyl-CoA and malonyl-CoA are transferred onto the protein complex by acetyl-CoA transacylase and malonyl-CoA transacylase (step 1 and step 2 in fig. 18.12a). The acceptor for the acetyl and malonyl groups is acyl carrier protein (ACP). ACP also carries all of the intermediates during fatty acid biosynthesis. The prosthetic group that binds these intermediates is... 

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... 

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. 

Pantothenic acid is part of the CoA molecule (for instance, as acetyl CoA, malonyl CoA, and succinyl CoA), and part of the acyl carrier protein of fatty acid biosynthesis. 

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