Succinyl-CoA transferase

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...

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

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

Fig. 5. Biosynthetic pathways for (I) 6-methylsalicylic acid and (II) the triacetic acid lactone. The structures of the intermediates have not been identified. The stereochemical course of the prochiral carbons (C-2 and C-4 in the triketide intermediate, C-3 and C-5 in 6-MSA) was investigated using R)- and (S)- [l- C,2- H]malonic acid extender substrate analogs in a coupled assay with 6-MSAS and succinyl-CoA transferase. The distinguishable hydrogens originating from the chiral malonyl CoA are labeled with H and H. Triacetic acid lactone synthesis is catalyzed by 6-MSAS in the absence NADPH...

MSA does not contain any chiral carbon centers. Before the aromatization of the six-membered ring occurs, two prochiral carbons (C-2 and C-4 in the six-carbon intermediate) evolve, each of which loses a hydrogen in the process of the dehydratization/aromatization steps. In addition, C-3 of the six-carbon intermediate forms a chiral center when the ketone is reduced to a hydroxyl by a ketoreductase activity (Fig. 5). The chirality of this hydroxyl carbon is unclear since the intermediate has not been isolated. It is also unknown if this carbon retains its chirality in an eight-carbon intermediate or whether the hydroxyl is eliminated by dehydration prior to the third condensation reaction. The stereospecificity at the prochiral C-2 and C-4 carbons in the reaction intermediates was addressed using chemically synthesized (] )- and (S)-[1- C, 2- H]malonate precursors which were enzymatically converted into CoA derivatives via succinyl CoA transferase [127,128]. Thus, the prochiral methylene in malonyl CoA was replaced by chiral, double-labeled (S)- or (J )-[1- C, 2- H]malonyl CoA substrates in the reaction mixture with 6-MSAS. The condensation is expected to occur with inversion of configuration and the intact methylene... 

In normal liver, only relatively small amounts of ketone bodies are formed. Their concentration in the blood is 0.5-D.8 mg per 100 ml plasma. The acetoacetate produced by this physiological K. is degraded in the peripheral musculature. Coenzyme A from succi-nyl-CoA is transferred to the acetoacetate by aceto-acetate succinyl-CoA transferase. Direct activation of acetoacetate by coenzyme A and ATP can also occur (Fig, 2). The acetoacetyl-CoA produced in either case is thioclastically cleaved into two molecules of acetyl-CoA, consuming a CoA molecule in the process. In carbohydrate deficiency (starvation, ketone-mia in ruminants), or deficient carbohydrate utilization (diabetes mellitus), K. is greatly increased. The cause of this pathological K. is a disturbance of the equilibrium between the degradation of fatty acids to acetyl-CoA and its utilization in the tricarboxylic acid cycle. The several-fold increase in the oxidation of the fatty acids leads under these conditions to an increase in the intracellular acetyl-CoA concentration. This leads to the condensation of 2 molecules of... 

The utilization of acetoacetate is controlled by the activity of the citric acid cycle. The reaction of acetoacetate succinyl CoA transferase provides an alternative to the reaction of succinyl CoA synthase (see Figure 5.18), and there will only be an adequate supply of succinyl CoA to permit conversion of acetoacetate to acetoacetyl CoA as long as the rate of citric acid cycle activity is adequate. 

The liver is a major metaboUc organ. It is the location of the urea cycle, purine synthesis and is the main site of lipid synthesis. It is also the site of KB synthesis, though it is unable to utilize KBs for energy as it lacks the enzymes 3-ketoacyl CoA transferase or succinyl CoA transferase (also known as thiophorase). Approximately 10 per cent of the liver s mass is glycogen, compared with 1—2 per cent of the mass of muscle. However, as there is far more muscle than liver in the body, about two-thirds of the body s glycogen by weight is stored in muscle. 

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. 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

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 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... 

Oxoacyl-CoA transferase (see fig. 18.8) is involved in the transfer of a CoASH from succinyl-CoA to acetoacetate to produce succinate and aceto-acetyl-CoA. A cursory examination of this reaction suggests a simple transfer of the CoA moiety. However, it is soon realized that the loss of an oxygen by the acetoacetate and the gain of an oxygen by the succinyl group present a dilemma. Produce a rational mechanism that explains the preservation of the thio-ester energy and solves this dilemma. Hint Consider a succinyl phosphate intermediate. 

Fig. 20.1. Generalized scheme of the main pathways of aerobic and anaerobic carbohydrate degradation in parasitic flatworms. The aerobic pathway is indicated by open arrows, whereas the anaerobic pathway (malate dismutation) is indicated by solid arrows. Abbreviations AcCoA, acetyl-CoA ASCT, acetateisuccinate CoA-transferase C, cytochrome c CI-CIV, complexes I—IV of the respiratory chain CITR, citrate FRD, fumarate reductase FUM, fumarate MAL, malate Methylmal-CoA, methylmalonyl-CoA OXAC, oxaloacetate PEP, phosphoenolpyruvate PROP, propionate Prop-CoA, propionyl-CoA PYR, pyruvate RQ, rhodoquinone SDH, succinate dehydrogenase SUCC, succinate Succ CoA, succinyl CoA UQ, ubiquinone.

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