Enzyme condensing

It is also worth noting that the carbon of the carboxyl group that was added to drive this reaction is the one removed by the condensing enzyme. Thus, all the carbons of acetoacetyl-ACP (and of the fatty acids to be made) are derived from acetate units of acetyl-CoA. 

The presence of a condensing enzyme which combines pyruvate and acetyl CoA to yield dtramalic add has been confirmed. 

Citric Acid with the Crystalline Condensing Enzyme. Nature 166,403 (1950). 

Members of the CHS/STS family of condensing enzymes are relatively modest-sized proteins of 40-47 kDa that function as homodimers. Each enzyme typically reacts with a cinnamoyl-CoA starter unit and catalyzes three successive chain extensions with reactive acetyl groups derived from enzyme catalyzed decarboxylation of malonyl-CoA.11 Release of the resultant tetraketide together with or prior to polyketide chain cyclization and/or decarboxylation yields chalcone or resveratrol (a stilbene). Notably, CHS and STS catalyze identical reactions up to the formation of the intermediate tetraketide. Divergence occurs during the termination step of the biosynthetic cascade as each tetraketide intermediate undergoes a distinct cyclization reaction (Fig. 12.2). 

SCHRODER, J., The chalcone/stilbene synthase-type family of condensing enzymes. In Comprehensive Natural Products Chemistry, vol. 1, Polyketides and Other Secondary Metabolites Including Fatty Acids and Their Derivatives (U. Sankawa ed.), Elsevier, Amersterdam, 1999, pp. 749-771. 

HUANG W, JIA, J EDWARDS, P., DEHESH, K., SCHNEIDER, G., LINDQVIST, Y., Crystal structure of P-ketoacyl-acyl carrier protein synthase II from E. coli reveals the molecular architecture of condensing enzymes, EMBO J., 1998,17, 1183-1191. 

Citrate (xi)-synthase [EC 4.1.3.7] (also known as citrate condensing enzyme, citrogenase, and oxaloacetate trans-acetase) catalyzes the reaction of acetyl-CoA with oxaloacetate and water to produce citrate and coenzyme A (in which acetyl-CoA <- (pro-35)-CH2COO ). Citrate (re)-synthase [EC 4.1.3.28] catalyzes the same reaction, albeit with the opposite stereochemistry (thus, acetyl-CoA (pro-3R)-CH2COO ). 

This enzyme [EC 4.1.3.2], also known as malate condensing enzyme and glyoxylate transacetylase, catalyzes the reaction of L-malate with coenzyme A to produce acetyl-CoA, water, and glyoxylate. 

ABORTIVE COMPLEXES MALATE DEHYDROGENASE MALATE SYNTHASE (S)-2-METHYLMALATE DEHYDRATASE Malate condensing enzyme,... 

It has been shown that the reaction center of multifunctional fatty acid synthases of yeast and animal cells comprises two SH-groups Cys-SH of the condensation enzyme, and pantetheine-SH attached to ACP. The... 

Fig. 3. Krebs citric acid cycle. Enzymes involved (1) Condensing enzyme (2) aconitase (3) isocitric acid (4) a-ketoglucaric acid dehydrogenase (4) a succinic acid thiokinasc (5) succinic acid dehydrogenase (6) fumarasc (7) malaic acid dehydrogenase. Abbreviations CA = citric acid ACOM = eij-aconitic acid KG = a-ketoglutaric acid SIC = succinic acid FA = fumaric acid MA = malic acid OA = oxalaceiic acid...

As the name anaerobic implies, the double bond of the fatty acid is inserted in the absence of oxygen. Biosynthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate /3-hydroxydecanoyl-ACP is reached (fig. 18.15). At this point, a new enzyme, /3-hydroxydecanoyl-ACP dehydrase, becomes involved. This dehydrase can form the a-j8 trans double bond, and saturated fatty acid synthesis can occur as previously discussed. In addition, this dehydrase is capable of isomerization of the double bond to a cis /3-y double bond as shown in figure 18.15. The /3-y unsaturated fatty acyl-ACP is subsequently elongated by the normal enzymes of fatty acid synthesis to yield pal-mitoleoyl-ACP (16 1A9). The conversion of this compound to the major unsaturated fatty acid of E. coli, cA-vacccnic acid (18 1A11), requires a condensing enzyme that we have not previously discussed, /3-ketoacyl-ACP synthase II, which shows a preference for palmitoleoyl-ACP as a substrate. The subsequent conversion to vaccenyl-ACP is cata-... 

Schroder J (1999) The chalcone/stilbene-synthase family of condensing enzymes. In Sankawa U (ed) Comprehensive natural products chemistry, vol 1. Pergamon, Oxford, pp 749-771... 

It has been assumed for many years that the first step in the elongase cycle, the condensation step, regulates the chain length of the final product. Direct evidence for this has been obtained in Arabidopsis, where the fatty acid elongationl (FAE1) gene encodes for the condensing enzyme (Millar and Kunst, 1997). The... 

Millar A. A. and Kunst L. (1997) Very-long-chain fatty acid biosynthesis is controlled through the expression and specificity of the condensing enzyme. Plant J. 12, 121-131. 

Condensation of acetyl-ACP and malonyl-ACP to form acetoacetyl-ACP, releasing free ACP and C02 (catalyzed by acyl-malonyl-ACP condensing enzyme). 

This first round of elongation produces the four-carbon butyryl-ACP. The cycle now repeats with malonyl-ACP adding two-carbon units in each cycle to the lengthening acyl-ACP chain. This continues until the 16-carbon palmitoyl-ACP is formed. This molecule is not accepted by the acyl-malonyl-ACP condensing enzyme, and so cannot be elongated further by this process. Instead it is hydrolyzed by a thioesterase to give palmitate and ACP. 

All of the enzymes needed for one cycle are clumped together to form two large proteins (ACP, the acyl carrier protein, and CE, the condensing enzyme) which associate in a stable dimer. The long side-chain passes the substrate from enzyme to enzyme so that synthesis can be continuous until the chain is finished and only then is the thiol ester hydrolysed. The chart on p. 1428 illustrates this. 

Oxaloacetate looking for a partner Thinks active acetate looks OK Condensing enzyme arranging a merger Makes a new citrate, and kicks out CoA. 

Ragsdale, S. W., and Wood, H. G., 1985, Acetate biosynthesis by acetogenic bacteria evidence that carbon monoxide dehydrogenase is the condensing enzyme that catalyzes the final steps of the synthesis, J. Biol. Chem. 260 397093977. 

Thiolase A family of condensing enzymes with diverse functions such as the formation... 

The basic assembly cycle for both polyketide and fatty acid biosynthesis is shown in Fig. 1 in which a starter unit, normally acetate is transferred to the ketosynthase (KS) or condensing enzyme which catalyzes a decarboxylative condensation with... 

We next examine the coordinated functioning of the mammalian fatty acid synthase. Fatty acid synthesis begins with the transfer of the acetyl group of acetyl CoA first to a serine residue in the active site of acetyl transferase and then to the sulfur atom of a cysteine residue in the active site of the condensing enzyme on one chain of the dimeric enzyme. Similarly, the malonyl group is transferred from malonyl CoA first to a serine residue in the active site of malonyl transferase and then to the sulfur atom of the phosphopantetheinyl group of the acyl carrier protein on the other chain in the dimer. Domain 1 of each chain of this dimer interacts with domains 2 and 3 of the other chain. Thus, each of the two functional units of the synthase consists of domains formed by different chains. Indeed, the arenas of catalytic action are... 

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