Succinyl CoA Synthase and Regulation of the Enzyme

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The amino acid responsible for activity is the phosphorylated histidine intermediate (HIS 246 alpha) which is the residue responsible for dephosphorylation of ATP and another site is suspected to be present in the beta subunit that ensures continued metabolism. It is also suspected that there is a nucleotide binding site at the N-terminal of beta subunit (Harel, 2014). This suggests that there are two active sites which are situated approximately 35A apart and that the HIS 246 alpha loop usually moves between them while catalysis is occurring. There is also GLU 208 alpha on the alpha subunit which interacts with the active HIS 246 residue in both the phosphorylated and dephosphorylated enzyme (Harel, 2014) As indicated above the histidine residue is the one involved in dephosphorylation or phosphorylation of ATP or ADP respectively. It has been proposed that the process involves a cooperative binding catalysis. Thus binding of ATP at one site enhances catalysis at another catalytic site (Schürmann et al, 2011). Binding of ATP occurs only in the presence of magnesium ion (Mg++) forming a complex which contains two ATP residue plus 2 phosphoric acid residues. If incubation is done this complex is converted to another one with 4 phosphoric acid residues per given protein. The complex with 4 phosphoric acid residues is the only one with the capability to react with succinate and CoA to give Succinyl CoA complex (Harel, 2014). This complex then releases phosphoric residues as many as bound succinate. The transfer of this phosphoric residue from the first active site correlates with the transfer to the second active site supporting the cooperative binding mechanism. These, therefore, means that both ADP and ATP can both be activating or inhibiting depending on which stage of catalysis they bind to the enzyme(Harel, 2014). These, therefore, support the reversibility of the catalysis. After the phosphorylation of the Succinyl-CoA .subsequent dephosphorylation, it is released and continues along the Krebs cycle as succinate.