What is succinyl CoA synthetase?
Succinyl coenzyme A synthetase ( SCS, also known as succinyl-CoA synthetase or succinate thiokinase or succinate-CoA ligase) is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate. The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule (either GTP or ATP) ...
How is the succinyl-CoA synthetase 587 enzyme structure calculated?
SUCCINYL-COA SYNTHETASE 587 enzyme is generally in excellent agreement with that calculated for an a & structure using the amino acid compositions of the separated subunits. Moreover, these data clearly rule out the possibility that the smaller subunit is derived from the larger one by proteolysis.
How can we study in vivo synthesis and Assembly of succinyl-CoA synthetase?
As a first step in studying the in vivo synthesis and assembly of the enzyme in the mammalian mitochondrial matrix, we have cloned and sequenced a 900 bp cDNA fragment that encodes most of the alpha subunit of rat liver succinyl-CoA synthetase.
What is the active site of succinyl-CoA synthetase?
The active site of Succinyl-CoA Synthetase seems to be more complicated than the other examples. In fact there appears to be two active sites each with a Coenzyme A in the active site. There does appear to be some similarities and generalizations about each active site.
Is Succinyl-CoA synthetase A transferase?
The last group of Class III CoA-transferases include enzymes involved in the metabolism of oxalate, carnitine, bile acids, toluene, and other aromatic compounds, as well as the succinyl-CoA:citramalate CoA-transferase that is involved in the 3-hydroxypropionate cycle of CO2-fixation.
Is Succinyl-CoA synthetase a regulatory enzyme?
Regulation. Succinyl-CoA synthetase is not a major regulator in the Krebs cycle, making it dependent on the steps prior. However, there has been evidence that a high-affinity GDP-binding site does allosterically regulate the activity of the enzyme.
Is succinyl-CoA an intermediate?
Succinyl-CoA is an important intermediate in the citric acid cycle, where it is synthesized from α-Ketoglutarate by α-ketoglutarate dehydrogenase (EC 1.2. 4.2) through decarboxylation, and is converted into succinate through the hydrolytic release of coenzyme A by succinyl-CoA synthetase (EC 6.2. 1.5).
What is the product of Succinyl-CoA synthetase?
Product Description Succinyl-CoA synthetase from E. coli is responsible for the coupled hydrolysis of succinyl-CoA to the production of ATP (or GTP) in the substrate-level phosphorylation step of the citric acid cycle (TCA).
Is succinyl-CoA synthetase a ligase?
Succinyl-CoA ligase, also called succinate synthase, is an enzyme in the Krebs cycle that converts succinyl-CoA to succinate and free coenzyme A, and converts ADP or guanosine diphosphate (GDP) to ATP or guanosine triphosphate (GTP) respectively (2,3). It is a mitochondrial matrix enzyme composed of two subunits.
Is succinate Thiokinase a ligase?
Succinyl coenzyme A synthetase (SCS, also known as succinyl-CoA synthetase or succinate thiokinase or succinate-CoA ligase) is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate.
What enzyme in the TCA cycle produces succinyl-CoA?
alpha-ketoglutarate dehydrogenaseExplanation: The citric acid cycle enzyme that catalyzes the reaction directly responsible for the production of succinyl-CoA is alpha-ketoglutarate dehydrogenase. Alpha-ketoglutarate dehydrogenase catalyzes the conversion of alpha-ketoglutarate, , and CoA-SH to succinyl-CoA, NADH, , and .
What is a succinyl group?
succinyl group (CHEBI:37952) is a divalent carboacyl group (CHEBI:23855) succinyl group (CHEBI:37952) is substituent group from succinic acid (CHEBI:15741) IUPAC Name. butanedioyl.
What does succinyl-CoA do in the citric acid cycle?
The citric acid cycle intermediate succinyl-CoA plays an important role in fatty acid and amino acid metabolism because it is the entry point of odd-chain fatty acids, propionate, and the branched chain amino acids valine and isoleucine into the citric acid cycle.
What is succinate in biology?
Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria. Recently, new roles for succinate outside metabolism have emerged.
Which amino acids form succinyl-CoA?
Succinyl-CoA can also be synthesized from propionyl-CoA by way of methylmalonyl-CoA, which is formed in the oxidation of branched-chain amino acids (e.g., valine, isoleucine) and in the terminal stage of oxidation of odd-chain-length fatty acids (Chapter 18).
What is the SCS enzyme?
SCS, also known as succinyl CoA ligase (SUCL), is the fifth enzyme of the TCA cycle. The protein is a heterodimeric enzyme, the α subunit of which, encoded by the SUCLG1 gene, couples the reversible conversion of succinyl-CoA to succinate bringing to the formation of a nucleoside triphosphate molecule (either GTP or ATP). The β subunit is encoded by either the SUCLG2 or the SUCLA2 gene, determining the specificity for GDP or ADP, respectively.
How is succinyl coa formed?
Succinyl-CoA can also be synthesized from propionyl-CoA by way of methylmalonyl-CoA, which is formed in the oxidation of branched-chain amino acids (e.g., valine, isoleucine) and in the terminal stage of oxidation of odd-chain-length fatty acids ( Chapter 18 ).
What is the phosphorylation of sugar in bacteria?
43 One such process is sugar import via the PTS system, an essential component of which is the histidine phosphocarrier protein (HPr). In PTS, the phosphate group of phosphoenolpyruvate is transferred first from component E1 to HPr, then to component E2 which phosphorylates the transported sugar. HPr is phosphorylated on N δ of His-I5, at the N terminus of the first α helix of this small (87 residues) protein, which has been extensively studied by NMR and X-ray crystallography. HPr is not self-phosphorylating, and its phosphohistidine is unstable as in NDP kinase. Although HPr phosphorylation by component E1 and excess phosphoenolpyruvate is easily achieved in solution, it is not practical in the crystal, and phosphorylation by phosphoramidate has not been reported. Thus, the phosphohistidine form has been studied by NMR. As there is no reporter proton to locate the phosphate group itself, NMR provides information only on the protein structure, which differs little from the free form. 44 , 45
How does methylmalonyl-CoA convert to L-isomer?
Methylmalonyl-CoA racemase converts D-methylmalonyl-CoA to the L-isomer by labilization of an α -hydrogen atom, followed by uptake of a proton from the medium.
What is the entry point of the citric acid cycle?
Entry via Succinyl-CoA. The citric acid cycle intermediate succinyl-CoA plays an important role in fatty acid and amino acid metabolism because it is the entry point of odd-chain fatty acids, propionate, and the branched-chain amino acids valine and isoleucine into the citric acid cycle.
What is the role of succinyl-coa in the citric acid cycle?
The citric acid cycle intermediate succinyl-CoA plays an important role in fatty acid and amino acid metabolism because it is the entry point of odd-chain fatty acids, propionate, and the branched chain amino acids valine and isoleucine into the citric acid cycle.
How is GTP converted to ATP?
GTP is converted to ATP by nucleoside-diphosphate kinase:
What are the active sites of succinyl coa synthetase?
Succinyl-CoA synthetase or Succinyl-CoA ligase is a tetramer with an active site on each subunit. This can be seen in the Jmol representation (the PDB code is 1CQJ). The two subunits are denoted alpha and beta. A phosphorylated histidine intermediate (HIS 246 alpha) is responsible for the dephosphorylation of ATP and it is suspected that there is another active site on the beta subunit that is responsible for the continued catalysis of the reaction. There is a suspected nucleotide binding site on the N-terminal of the beta subunit which would imply that there are two active sites roughly 35 A apart from each other and that the HIS 246 alpha loop moves between them during catalysis. On the alpha subunit it has been shown that GLU 208 alpha interacts in some way with the active HIS 246 alpha residue in the phosphorylated and dephosphorylated enzyme and it is supposed that GLU 197 beta serves a similar purpose on the beta subunit.
What is the name of the enzyme that catalyzes the reversible reaction of succinyl?
Succinyl-CoA synthetase or succinate-CoA ligase catalyzes the reversible reaction of succinyl-CoA + NDP + Pi <-> succinate + CoA + NTP (where N is either adenosine or guanosine. It can be found in Escherichia coli and is the fifth step in the citric acid cycle. Due to its involvement in the citric acid cycle it is very important in all living cells that use oxygen as a part of cellular respiration. This entire process (Citric acid cycle) is necessary in producing one GTP or ATP, three NADHs, and two carbon dioxides. See also:
What happens after succinyl-coa is phosphorylated?
After the Succinyl-CoA has been phosphorylated and subsequently dephosphorylated it is release as succinate which continues along the Krebs cycle.
Does sucinyl coa sythetase have a steady state kinetic pattern?
It has been shown in E. coli that Succinyl Coa sythetase does not have a steady state kinetic pattern. What has been seen is a kinetic pattern that is consistent when the sequential addition of all substrates is done, to form a quaternary structure before releasing any products. This would then give evidence of a limitation on the initial rate kinetics. This is because the order of substrate attachment and product release is limited. And as seen previously the reaction is dependent on the presence of either GDP and GTP or ATP and ADP and the amount of concentrations that they are present at.
Which residue is involved in the dephosphorylation of ATP?
The histidine residue involved in the (de)phosphorylation of (ATP)ADP acts through the following mechanism.
Is succinyl coa synthetase a regulator?
Succinyl-CoA synthetase is not a major regulator in the Krebs cycle, making it dependent on the steps prior. However, there has been evidence that a high-affinity GDP-binding site does allosterically regulate the activity of the enzyme. It has also been seen that the binding of GDP to these allosteric sites actually leads to an increase in the rate of phosphorylation of Succinyl-Coa synthetase. This could be due to the fact that GDP is probably altering the affinity of the enzyme for GTP.
Function
Structure
- Succinyl-CoA synthetase or Succinyl-CoA ligase is a tetramer with an active site on each subunit. This can be seen in the Jmol representation (the PDB code is 1CQJ). The two subunits are denoted alpha and beta. A phosphorylated histidine intermediate (HIS 246 alpha) is responsible for the dephosphorylation of ATP and it is suspected that there is a...
Mechanism
- The histidine residue involved in the (de)phosphorylation of (ATP)ADP acts through the following mechanism. A cooperative binding catalysis mechanism has been proposed and it has been shown that binding of ATP at one catalytic site promotes catalytic activity at another catalysis site. It has been shown that the enzyme will bind with ATP in the presence of Mg+2 to form a co…
Bound Form of Succinyl-Coa Synthetase
- The form of succinyl-CoA synthetase shown here (PDB code 1CQI) is the bound form with two ADP-Mg complexes (the ADP is highlighted and the Mg is in green). As seen here, the Histidine 246residues on both the alpha and beta subunits are present and interacting with the lone Pi group while the ADP group is bound elsewhere on the subunit.
Kinetics
- It has been shown in E. coli that Succinyl Coa sythetase does not have a steady state kinetic pattern. What has been seen is a kinetic pattern that is consistent when the sequential addition of all substrates is done, to form a quaternary structure before releasing any products. This would then give evidence of a limitation on the initial rate kinetics. This is because the order of substra…
Regulation
- Succinyl-CoA synthetase is not a major regulator in the Krebs cycle, making it dependent on the steps prior. However, there has been evidence that a high-affinity GDP-binding site does allosterically regulate the activity of the enzyme. It has also been seen that the binding of GDP to these allosteric sites actually leads to an increase in the rate of phosphorylation of Succinyl-Co…