Succinyl transferase

CPB3787). 4//-Pyran-2,6-dicarboxylic acid is a weak inhibitor of tetra-hydrodipicolinate /V-succinyl transferase (86JBC6160). 

Figure 25 The arginine succinyl transferase (AST) pathway consists of five enzymes W -succinyltransferase (AST), W -succinylarginine dihydrolase (SADH), N -succinylornithine 5-aminotransferase (SOAT), W -succinylglutamate 5-semialdehyde dehydrogenase (SGSD), and W -succinylglutamate desuccinylase (SGDS).

So, the biosynthesis of methionine (Met, M), the first of the essential amino adds to be considered (Scheme 12.13), begins by the conversion of aspartate (Asp, D) to aspartate semialdehyde in the same way glutamate (Glu, E) was converted to glutamate semialdehyde (vide supra. Scheme 12.6). Phosphorylation on the terminal carboxylate of aspartate (Asp, D) by ATP in the presence of aspartate kinase (EC 2.7.2.4) and subsequent reduction of the aspart-4 yl phosphate by NADPH in the presence of aspartate semialdehyde dehydrogenase (EC 1.2.1.11) yields the aspartate semialdehyde. The aspartate semialdehyde is further reduced to homoserine (homoserine oxoreductase, EC 1.1.1.3) and the latter is succinylated by succinyl-CoA with the liberation of coenzyme A (CoA-SH) in the presence of homoserine O-succinyl-transferase (EC 2.3.1.46). Then, reaction with cysteine (Cys, C) in the presence of cystathionine y-synthase (EC 2.5.1.48) produces cystathionine and succinate. In the presence of the pyridoxal phosphate protein cystathionine P-lyase (EC 4.4.1.8), both ammonia and pyruvate are lost from cystathionine and homocysteine is produced. Finally, methylation on sulfur to generate methionine (Met, M) occurs by the donation of the methyl from 5-methyltetrahydrofolate in the presence of methonine synthase (EC 2.1.1.13). 

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... 

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. 

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... 

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. 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

Table 1.4.15 Data from a acid transferase deficiency patient affected with succinyl coenzyme A 3-oxo ... 

Succinyl coenzyme A 3-oxo acid transferase catalyses the transformation of ACAC into acetoacetyl coenzyme A in the mitochondria of extra-hepatic tissues. This enzyme defect may be suggested in cases of severe ketoacidosis often associated with neurologic dysfunction [16]. 

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... 

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

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.

The pathway can be divided into two metabolic cycles (Figure 3.4). In the first cycle, acetyl-CoA is carboxylated to malonyl-CoA, which is subsequently reduced and converted into propionyl-CoA via 3-hydroxypropionate as a free intermediate. Propionyl-CoA is carboxylated to methylmalonyl-CoA, which is subsequently converted to succinyl-CoA the latter is then used to activate L-malate by succinyl-CoA L-malate coenzyme A transferase, which forms L-malyl-CoA and succinate. Succinate is oxidized to L-malate via conventional steps. L-Malyl-CoA, the second characteristic intermediate of this cycle, is cleaved by L-malyl-CoA/P-methylmalyl-CoA lyase, thus regenerating the starting molecule acetyl-CoA and releasing gly-oxylate as a first carbon-fixation product [27]. 

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