Acetyl CoA hydrolase

Figure 3. Mitochondrial fatty acid oxidation. Long-chain fatty acids are converted to their CoA-esters as described in the text, and their fatty-acyl-groups transferred to CoA in the matrix by the concerted action of CPT 1, the acylcarnitine/carnitine exchange carrier and CPT (A) as described in the text. Medium-chain and short-chain fatty acids (Cg or less) diffuse directly into the matrix where they are converted to their acyl-CoA esters by a acyl-CoA synthase. The mechanism of p-oxidation is shown below (B). Each cycle of P-oxidation removes -CH2-CH2- as an acetyl unit until the fatty acids are completely converted to acetyl-CoA. The enzymes catalyzing each stage of P-oxidation have different but overlapping specificities. In muscle mitochondria, most acetyl-CoA is oxidized to CO2 and H2O by the citrate cycle (Figure 4) some is converted to acylcamitine by carnitine acetyltransferase (associated with the inner face of the inner membrane) and exported from the matrix. Some acetyl-CoA (if in excess) is hydrolyzed to acetate and CoASH by acetyl-CoA hydrolase in the matrix. Enzymes ...

Thiolester hydrolases (EC 3.1.2) play an important role in the biochemistry of lipids. They catalyze the hydrolysis of acyl-coenzyme A thiolesters of various chain lengths to free fatty acids and coenzyme A. The current list of over 20 specific enzymes includes acetyl-CoA hydrolase (EC 3.1.2.1), pal-mi toy 1-Co A hydrolase (EC 3.1.2.2), and an acyl-CoA hydrolase (EC 3.1.2.20) of broad specificity for medium- to long-chain acyl-CoA [128],... 

These results were recently confirmed by Roughan and Slack (1977). The wide distribution of acetyl-CoA synthetase in leaf, seed, and tuber tissue coupled with the presence of an acetyl-CoA hydrolase suggests that these two enzymes may be involved in the transport of acetate from a site of its synthesis (namely, the mitochondria) in a form that is essentially metaboli-cally inert (as acetate) to a site where it is effectively converted and utilized as a thioester derivative. 

Jacobson and Stumpf, in 1972, reported a very rapid entry of free acetate into isolated chloroplasts. The half-time for equilibration across the envelope membrane was less than 5 s. However, acetyl-CoA was essentially nonpermeable across the chloroplast envelope membrane. That a coupled acetyl-CoA hydrolase-acetyl-CoA synthetase system may serve as an efficient transport unit is suggested by the observation that free acetate is rarely found in the plant cell. 

Fig. 2.11. Acetic acid formation pathways in yeasts. 1 = pyruvate decarboxylase 2 = alcohol dehydrogenase 3 = pyruvate dehydrogenase 4 = aldehyde dehydrogenase 5 = acetyl-CoA hydrolase 6 = acetyl-CoA synthetase...

The activity of carbamoyl phosphate synthase I is determined by A -acetylglutamate, whose steady-state level is dictated by its rate of synthesis from acetyl-CoA and glutamate and its rate of hydrolysis to acetate and glutamate. These reactions are catalyzed by A -acetylglu-tamate synthase and A -acetylglutamate hydrolase, respectively. Major changes in diet can increase the concentrations of individual urea cycle enzymes 10-fold to 20-fold. Starvation, for example, elevates enzyme levels, presumably to cope with the increased production... 

Figure 11.5 Reactions of the fatty acid synthase complex. A single multi-subunit enzyme is responsible for the conversion of acetyl-CoA to palmitate. The subunits in the enzyme are (i) acetyltransferase, (ii) malonyltransferase, (iii) oxoacyl synthase, (iv) oxoacyl reductase, (v) hydroxyacyl dehydratase, (vi) enoyl reductase. Finally, a separate enzyme, thioester hydrolase, hydrolyses palmitoyl-CoA to produce palmitate (vii).

Fig. 7. Enzyme-coupled assay in which the hydrolase-catalyzed reaction releases acetic acid. The latter is converted by acetyl-CoA synthetase (ACS) into acetyl-CoA in the presence of (ATP) and coenzyme A (CoA). Citrate synthase (CS) catalyzes the reaction between acetyl-CoA and oxaloacetate to give citrate. The oxaloacetate required for this reaction is formed from L-malate and NAD in the presence of L-malate dehydrogenase (l-MDH). Initial rates of acetic acid formation can thus be determined by the increase in adsorption at 340 nm due to the increase in NADH concentration. Use of optically pure (Ry- or (5)-acetates allows the determination of the apparent enantioselectivity i app i81)-...

The nickel enzymes covered in this article can be divided into two groups redox enzymes and hydrolases. The five Ni redox enzymes are hydrogenase, CO dehydrogenase (CODH), acetyl-CoA synthase (ACS), methyl-Coenzyme M reductase (MCR), and superoxide dismutase (SOD). Glyoxalase-I and urease are Ni hydrolases. Ni proteins that are not enzymes are not covered, because they have been recently reviewed. These include regulatory proteins (NikR) and chaperonins and metal uptake proteins (CooJ, CooE, UreE, and ABC transporters). A recent crystal structure of NikR, shown in Figure l(i), is a notable recent achievement in this area. ... 

For example, acetyl-CoA produces ethyl acetate by ethanolysis. In disrupted plant tissues, for example during production of juices, esters are rapidly broken down by various hydrolases, which results in a change of the flavour character. Also, many esters of aromatic acids are components of the aroma of fruits and spices. 

Chapter 5 presents a simple method for making acyl-ACPs for use in PKS enzyme assays. This allows the synthesis of more realistic substrate mimics, where the full phosphopantetheine linker chain tethers the acyl chain to the ACP. Matthew went on to use these products to probe the substrate specificity of the acyl hydrolase from the pederin PKS, and demonstrate that its major housekeeping role is probably in targeting unwanted acetyl-ACP, which may be derived from acetyl-CoA during initial activation of the PKS by the promiscuous phosphopantetheine transferases. 

The intracellular biodegradation pathway of PHB is illustrated and combined with the biosynthetic pathway in Fig. 14.9 (Muller and Seebach, 1993 Senior and Dawes, 1971, 1973 Doi et al, 1992b Haywood et al, 1988). PHB is first depolymerized by PHB depolymerase to produce the 7 -3-hydroxybutyric acid (7 -3-HB) or 7 -3HB oligomers. The latter is further depolymerized by oligomer hydrolase to 7 -3HB monomer. 7 -3HB is dehydrogenated with NAD into acetoacetic acid which follows esterification with CoA-SH to produce acetoacetyl-CoA by the action of acetoacetyl-CoA synthase with the aid of ATP. The acetoacetyl-CoA is degraded into acetyl-CoA by /3-ketothiolase. This compound then enters the tricarboxylic acid (TCA) cycle to transform carbon dioxide and water under aerobic conditions. 

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