Succinyl-CoA synthetase succinate

Succinyl CoA synthetase (succinate thiokinase) catalyzes a substrate-level phosphorylation of GDP to GTP. 

The subsequent cleavage of the thio-ester succinylCoA into succinate and coenzyme A by succinic acid-CoA ligase (succinyl CoA synthetase, succinic thiokinase) is strongly exergonic and is used to synthesize a phosphoric acid anhydride bond ( substrate level phosphorylation , see p. 124). However, it is not ATP that is produced here as is otherwise usually the case, but instead guanosine triphosphate (CTP). However, GTP can be converted into ATP by a nucleoside diphosphate kinase (not shown). 

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. 

Isocitrate Dehydrogenase a Ketoglutarate Dehydrogenase Complex Succinyl-CoA Synthetase Succinate Dehydrogenase... 

The cleavage of the thioester bond of succinyl CoA is coupled to the phosphorylation of a purine nucleoside diphosphate, usually GDP. This reaction is catalyzed by succinyl CoA synthetase (succinate thiokinase). This enzyme is an a2 2 heterodimer the functional unit is one a(3 pair. The mechanism is a clear example of energy transformations energy inherent in... 

Isocitrate dehydrogenase a-Ketoglutarate dehydrogenase Succinyl-CoA synthetase Succinate dehydrogenase Fumarase... 

Lsocitrate Dehydrogenase—The First Oxidadon in die Cycle m-Ketoglutarate Dehydrogenase—A Second Decarboxylation Succinyl-CoA Synthetase—A Substrate-Level Phosphoryladon Succinate Dehydrogenase—An Oxidadon Involving FAD... 

The mechanism of succinyl-CoA synthetase is postulated to involve displacement of CoA by phosphate, forming succinyl phosphate at the active site, followed by transfer of the phosphoryl group to an active-site histidine (making a phosphohistidine intermediate) and release of succinate. The phosphoryl moiety is then transferred to GDP to form GTP (Figure 20.13). This sequence of steps preserves the energy of the thioester bond of succinyl-CoA in a series of high-energy intermediates that lead to a molecule of ATP ... 

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. 

Succinyl-CoA synthetase (GDP) [EC 6.2.1.4], also known as succinate CoA ligase, catalyzes the reversible reaction of GTP with succinate and coenzyme A to produce GDP, succinyl-CoA, and orthophosphate. The nucleotide substrate can be replaced with ITP and itaconate can substitute for succinate. 

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-... 

Succinate thiokinase (also called succinyl CoA synthetase) cleaves the high-energy thioester bond of succinyl CoA (see Figure 9.6). This reaction is coupled to phosphorylation of GDP to GTP. GTP and ATP are energetically interconvertible by the nucleoside diphos phate kinase reaction ... 

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. 

Conversion of succinyl CoA to succinate [catalyzed by succinyl CoA synthetase the reaction requires inorganic phosphate and GDP (or ADP)]. 

Succinyl CoA is converted to succinate (4C) by succinyl CoA synthetase. The reaction uses the energy released by cleavage of the succinyl-CoA bond to synthesize either GTP (mainly in animals) or ATP (exclusively in plants) from P and, respectively, GDP or ADP. 

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. 

STEPS s-6 Hydrolysis and dehydrogenation of succinyl CoA. Succinyl CoA is hydrolyzed to succinate in step 5. The reaction is catalyzed by succinyl CoA synthetase and is coupled with phosphorylation of guanosine diphosphate (GDP) to give guanosine triphosphate (GTP). The overall transformation is similar to that of step 8 in glycolysis (Figure 29.4), in which a thiol ester is converted into an acyl phosphate and a phosphate group is then transferred to ADP. 

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.

The answer is b. (Murray, pp 182-189. Scriver, pp 1521-1552. Sack, pp 121-138. Wilson, pp 287-317.) Reducing equivalents are produced at four sites in the citric acid cycle. NADH is produced by the isocitrate dehydrogenase-catalyzed conversion of a-ketoglutarate to succinyl CoA and by the malate dehydrogenase-catalyzed conversion of malate to oxaloacetate. FADH, is produced by the succinate dehydrogenase-catalyzed conversion of succinate to fumarate. Succinyl CoA synthetase catalyzes the formation of succinate from succinyl CoA, with the concomitant phosphorylation of GDP to GTP... 

Succinyl-CoA, which is produced in the tricarboxylic acid cycle, is normally converted to succinate by the action of succinyl-CoA synthetase in catalyzing reaction (26). 

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