Succinyl thiokinase

The citric acid cycle One is generated directly in the cycle at the succinyl thiokinase step (Figure... 

Aconitase catalyzes the isomerization of citrate to isodtrate, isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate, and a-ketoglutarate dehydrogenase catalyzes the oxidative decarboxylation of a-keto-glutarate to succinyl-CoA. Succinyl-CoA and the remaining intermediates are the 4-carbon intermediates of the Krebs cycle. Succinyl thiokinase catalyzes the release of coenzyme A from succinyl-CoA and the production of GTP. Succinate dehydro-... 

The overall scheme for glucose oxidation was given in Eq. (5.13). Reduction of 6 O2 in the body results in the production of 12 molecules of water. However, Eq. (5.13) shows that only 6H2O are produced. Why are I2H2O not listed The catabolism of one molecule of glucose results in the production of two molecules of pyruvate. Complete oxidation of two pyruvates results in the use of six molecules of water. Water is used by citrate synthase for the hydrolysis of coenz5mie A from acetyl-CoA, by succinyl thiokinase for the hydrolysis of coenz5one A from suc-cinyl-CoA, and by fumarase for the hydration of fumarate. 

Water is produced in this manner at such points as succinyl thiokinase and ATP synthase. The water molecules involved are not included in the calculation of the waters of oxidation. 

The resulting succinyl-CoA serves as substrate to succinyl thiokinase, an enzyme typical of mitochondria and many prokaryotes. 

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 (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). 

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... 

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 ... 

The generation of GTP by succinate thiokinase is another example of substrate-level phosphorylation (see p. 100). [Note Succinyl CoA is also produced from propionyl CoA derived from the metabolism of fatty acids with an odd number of carbon atoms (see p. 191), and from metabolism of several amino acids (see p. 264). 

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. 

Succinate Thiokinase Couples the Conversion of Succinyl-CoA to Succinate with the Synthesis of GTP... 

The reaction is complex and involves an intermediate in which a phosphate is attached to a histidine residue of the succinate thiokinase enzyme. Probably CoA is first displaced by inorganic phosphate, forming succinyl phosphate. A nitrogen atom of a specific histidine residue then attacks phosphorus, displacing succinate and forming an A-phos-phoryl derivative. In the final step GDP attacks the phosphorus atom of that derivative forming GTP. The role of GTP in this reaction is played by ATP in some organisms. 

The products of the isoleucine catabolic pathway are propionyl-CoA and ace-tyl-CoA valine catabolism produces one molecule of propionyl-CoA and two molecules of carbon dioxide. Propionyl-CoA is further cataboli25ed to succinyl-CoA, an intermediate of the Krebs cycle (Figure 8.7). This pathway is also used for catabolism of the short-chain fatty acid propionic acid, after its conversion to the thiol ester form by thiokinase. The first step in propionyl-CoA breakdown is catalyzed by propionyl-CoA carboxylase, a biotin-requiring enzyme. The second step is catalyzed by methylmalonyl-CoA mutase, a vitamin Bi2-requiring enzyme. 

In this complex reaction catalyzed by succinyl-CoA synthase (succinate thiokinase), the energy-rich thioester linkage of succinyl-CoA is hydrolyzed with release of free energy that is conserved in the substrate phosphorylation of GDP with phosphate to form GTP ... 

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