CoA transferases

In peripheral tissues acetoacetate exported by the liver reacts with succinyl-CoA formed in the citrate cycle to give acetoacetyl-CoA and succinate catalyzed by a specific CoA transferase. 

When ketone bodies are being metabolized in extra-hepatic tissues there is an alternative reaction catalyzed by succinyl-CoA-acetoacetate-CoA transferase (thio-phorase)—involving transfer of CoA from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA (Chapter 22). 

In extrahepatic tissues, acetoacetate is activated to acetoacetyl-CoA by succinyl-CoA-acetoacetate CoA transferase. CoA is transferred from succinyl-CoA to form acetoacetyl-CoA (Figure 22-8). The acetoacetyl-CoA is split to acetyl-CoA by thiolase and oxidized in the citric acid cycle. If the blood level is raised, oxidation of ketone bodies increases until, at a concentration of approximately 12 mmol/L, they saturate the oxidative machinery. When this occurs, a large proportion of the oxygen consumption may be accounted for by the oxidation of ketone bodies. 

Human succinyl CoA-transferase E. coll acetate CoA transferase a E. coll acetate CoA transferase b... 

Fig. 1. The metabolic cycle for the synthesis and degradation of poly(3HB). (1) 3-ketothiolase (2) NADPH-dependent acetoacetyl-CoA reductase (3) poly(3HB) synthase (4) NADH-dependent acetoacetyl-CoA reductase (5), (6) enolases (7) depolymerase (8) d-(-)-3-hydroxybutyrate dehydrogenase (9) acetoacetyl-CoA synthetase (10) succinyl-CoA transferase (11) citrate synthase (12) see Sect. 3...

In combination of this polymerase with purified propionyl-CoA transferase of Clostridium propionicum, a two-enzyme in vitro PHB biosynthesis system was established which allowed the PHB synthesis from (R)-hydroxybutyric acid as substrate [119]. In this way, the PHB synthesis was independent of the consumption of the expensive CoA, and hence PHA could be readily produced in a semipreparative-scale... 

The enzymes responsible for their metabolism, d-P-hydroxybutyrate dehydrogenase, acetoacetate-succinyl-CoA transferase and acetoacetyl-CoA-thiolase, are present in... 

Tildon, J. T. and Cornblath, M. Succinyl-CoA 3-ketoacid CoA-transferase deficiency. A cause for ketoacidosis in infancy. /. Clin. Invest. 51 493 98,1972. 

Acetoacetate picked up from the blood is activated in the mitochondria by succinyl CoA ace-toacetyl CoA transferase (common name thiophorase), an enzyme present only in extrahepatic tissues 3-hydroxybutyrate is first oxidized to acetoacetate. Because the liver lacks this enzyme, it carmot metabolize the ketone bodies. 

Degradation of acetoacetate to acetyl CoA takes place in two steps (not shown). First, acetoacetate and succinyl CoA are converted into acetoacetyl CoA and succinate (enzyme 3-oxoacid-CoA transferase 2.8.3.5). Acetoacetyl CoA is then broken down by p-oxidation into two molecules of acetyl CoA (see p. 164), while succinate can be further metabolized via the tricarboxylic acid cycle. 

This enzyme [EC 4.1.3.6] (also known as citrate (pro-35)-lyase, citrase, citratase, citritase, citridesmolase, and citrate aldolase) catalyzes the conversion of citrate to acetate and oxaloacetate. Citrate lyase can be dissociated into subunits, two components of which are identical with citrate CoA-transferase [EC 2.8.3.10] and citryl-CoA lyase [EC 4.1.3.34]. 

This enzyme [EC 2.S.3.5], also known as succinyl-CoA 3-ketoacid CoA-transferase and 3-oxoacid CoA-transferase, catalyzes the reversible reaction of succinyl-CoA with a 3-oxo acid to produce succinate and a 3-oxo-acyl-CoA derivative. 

Succinyl-CoA acetate CoA transferase (acetate/succinate CoA transferase (ASCT), 2.8.3.8) catalyzes the transfer of the CoA moiety between acetate and succinate and produces the hydrogenosomal end product, acetate. This activity was first detected in the hydrogenosomes of T. foetus in the mid-1970s (Lindmark 1976) and subsequently in T. vaginalis as well (Steinbiichel and Muller 1986). However, the enzyme has not been purified or characterized in any detail, nor has it been sequenced. During the preliminary analysis of the... 

Fig. 1 Enzymes localized to B. hominis mitochondrial-like organelle. The enzymes are 1 malic enzyme, 2 pyruvate NADP oxidoreductase, 3 acetate succinate CoA transferase, 4 succinate thiokinase, 5 a-ketoglutarate dehydrogenase, 6 isocitrate dehydrogenase, and 7 aconitase...

Cyclophilin Carbonic anhydrase Iriose phosphate isomerase Carboxypeptidase A Phosphoglucomutase Succinyl-CoA transferase Urease... 

CoA, the coenzyme A derivative of acetoacetate, reduces its reactivity as a substrate for /3-ketoacyl-CoA transferase (an enzyme of lipid metabolism) by a factor of 106. Although this requirement for adenosine has not been investigated in detail, it must involve the binding energy between enzyme and substrate (or cofactor) that is used both in catalysis and in stabilizing the initial enzyme-substrate complex (Chapter 6). In the case of /3-ketoacyl-CoA transferase, the nucleotide moiety of coenzyme A appears to be a binding handle that helps to pull the substrate (acetoacetyl-CoA) into the active site. Similar roles may be found for the nucleoside portion of other nucleotide cofactors. 

In extraliepatic tissues, d-/3-hydroxybutyrate is oxidized to acetoacetate by o-/3-hydroxybutyrate dehydrogenase (Fig. 17-19). The acetoacetate is activated to its coenzyme A ester by transfer of CoA from suc-cinyl-CoA, an intermediate of the citric acid cycle (see Fig. 16-7), in a reaction catalyzed by P-ketoacyl-CoA transferase. The acetoacetyl-CoA is then cleaved by thiolase to yield two acetyl-CoAs, which enter the citric acid cycle. Thus the ketone bodies are used as fuels. 

Example 3-Oxoacyl-CoA transferase (Y = —S—CoA) B. Addition to a carbonyl group aldol condensation... 

---