Enzymes succinyl CoA synthetase

Succinyl-CoA + Pi + GDP <=> Succinate + GTP + CoASH Enzyme Succinyl-CoA Synthetase... 

Succinate is an intermediate of the citric acid cycle (and the glyoxylate cycle) produced by action of the enzyme succinyl-CoA synthetase on succinyl-CoA. Succinate is converted to fumarate by action of the enzyme succinate dehydrogenase (with formation of FADH2)... 

Succinyl-CoA is an intermediate of the citric acid cycle produced by decarboxylation of oi-ketoglutarate. The reaction is catalyzed by the a-ketoglutarate dehydrogenase enzyme complex. Succinyl-CoA is converted to succinate (with formation of GTP) in a reaction catalyzed by the enzyme succinyl-CoA synthetase. 

PEPCK requires, in addition to oxaloacetate, its second substrate GTP or ITP. If the enzyme is located in the mitochondria, then GTP will also be necessary in the mitochondria. GTP is generated in substrate level phosphorylation by the citric acid cycle enzyme succinyl-CoA synthetase (reaction 3.9), which is present in the mitochondrial matrix. 

Succinyl-CoA is converted to succinate by the enzyme succinate thiokinase (succinyl-CoA synthetase). This is the only example in the citric acid cycle of substrate-level phosphorylation. Tissues in which glu-coneogenesis occurs (the hver and kidney) contain two isoenzymes of succinate thiokinase, one specific for GDP and the other for ADP. The GTP formed is used for the decarboxylation of oxaloacetate to phos-phoenolpymvate in gluconeogenesis and provides a regulatory hnk between citric acid cycle activity and the withdrawal of oxaloacetate for gluconeogenesis. Nongluconeogenic tissues have only the isoenzyme that uses ADP. 

Fig. 2 SDS-polyacrylamide gel electrophoresis of T. vaginalis hydrogenosomes purified by isopycnic centrifugation on a Percoll gradient. 1 PFOR 2 malic enzyme, 64-kDa hy-drogenase, and Cpn 60 3 succinyl CoA synthetase fi subunit 4 Hmp35 5 succinyl CoA synthetase a subunit 6 Hmp31 (ATP/ADP carrier) 7 adenylate kinase 8 thiol peroxidase. Well-resolved but unmarked bands mostly belong to malic enzyme fragments or unknown proteins. Proteins were identified by mass spectroscopy. The 12% gel is stained with Coomassie Brilliant Blue R 250 (authors original)...

Succinyl-CoA synthetase (SCS), also known as succinate thiokinase (STK) or succinate CoA ligase ( 6.2.1.4-5), is so far the only known hydrogenosomal enzyme directly involved in energy conservation. The protein catalyzes the reversible, substrate-level phosphorylation of ADP or GDP to the respective triphosphate at the expense of the high-energy thioester bond of succinyl-CoA. Succinate and CoA are released in the reaction. The I vaginalis enzyme... 

The enzyme that catalyzes this reversible reaction is called succinyl-CoA synthetase or succinic thioki-... 

Balance Sheet for the Citric Acid Cycle The citric acid cycle has eight enzymes citrate synthase, aconitase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, succinyl-CoA synthetase, succinate dehydrogenase, fumarase, and malate dehydrogenase. 

Succinyl CoA is cleaved by succinate thiokinase (also called succinyl CoA synthetase), producing succinate and ATP (or GTP). This is an example of substrate-level phosphory lation. Succinate is oxidized to fumarate by succinate dehydrogenase, producing FADH2. The enzyme is inhibited by oxaloacetate. Fumarate is hydrated to malate by fumarase (fumarate hydratase), and malate is oxidized to oxaloacetate by malate dehy drogenase, producing NADH. 

An enzyme catalyzing a reaction similar to that of acetyl-CoA synthetase is succinyl-CoA synthetase... 

Most tissues oxidize the acetyl-CoA produced during P-oxidation to C02 and water via the TCA cycle. During fasting, however, the liver utilizes the intermediates of the TCA cycle as gluconeogenic substrates. Under these conditions, the Ever converts acetyl-CoA to ketone bodies (acetoacetate and P-hydroxybutyrate) (Figure 32-5). Most other peripheral tissues can oxidize ketone bodies by the pathway shown in the figure. After entering the mitochondria, acetoacetate reacts with succinyl-CoA to form acetoacetyl-CoA, a reaction that is catalyzed by 3-oxoacid-CoA transferase. Alternatively, acetoacetyl-CoA is formed by direct activation of acetoacetate by the enzyme acetoacetyl-CoA synthetase. Acetoacetyl-CoA is then cleaved to form two molecules of acetyl-CoA by acetoacetyl-CoA thiolase.As noted earlier in... 

Figure 17.13. Reaction Mechanism of Succinyl CoA Synthetase. The formation of GTP at the expense of succinyl CoA is an example of suhstrate-level phosphorylation. The reaction proceeds through a phosphorylated enzyme intermediate.

Figure 17.14. Structure of Succinyl CoA Synthetase. The enzyme is composed of two subunits. The a subunit contains a Rossmann fold that binds the ADP component of CoA, and the (3 subunit contains a nucleotideactivating region called the ATP-grasp domain. The ATP-grasp domain is shown here binding a molecule of ADP. The histidine residue picks up the phosphoryl group from near the CoA and swings over to transfer it to the nucleotide bound in the ATP-grasp domain.

J. D. Johnson, W.W. Muhonen, and D.O. Lambeth. 1998. Characterization of the ATP- and GTP-specific succinyl-CoA synthetases in pigeon The enzymes incorporate the same subunit Biol. Chem. 273 27573-27579. (PubMed)... 

Enzymes a) citrate synthase b) aconitase c) isocitrate dehydrogenase d) a-oxoglutarate dehydrogenase e) succinyl CoA synthetase f) succinate dehydrogenase g) fumarase h) malate dehydrogenase i) nucleoside diphosphokinase. 

This reaction is the only step in the citric acid cycle that directly yields a compound with high phosphoryl-transfer potential. Some mammalian succinyl CoA synthetases are specific for GDP and others for ADP. The . coli enzyme uses either GDP or ADP as the phosphoryl-group acceptor. We have already seen that GTP is an important component of signal-transduction systems (Chapter 14). Alternatively, its 7 phosphoryl group can be readily transferred to ADP to form ATP, in a reaction catalyzed by nuc/eostde diphosphokinase. 

Figure 17,13 Reaction mechanism of succinyl CoA synthetase. The reaction proceeds through a phosphorylated enzyme intermediate. (1) Orthophosphate displaces coenzyme A, which generates another energy-rich compound, succinyl phosphate. (2) A histidine residue removes the phosphoryl group with the concomitant generation of succinate and phosphohistidine. (3) The phosphohistidine residue then swings over to a bound nucleoside diphosphate, and (4) the phosphoryl group is transferred to form the nucleoside triphosphate.

---