Is citrate synthase inhibited by ATP?
Citrate synthase is responsible for the rate of reaction in the first step of the cycle when the acetyl-CoA is combined with oxaloacetic acid to form citrate. It is inhibited by high concentrations of ATP, acetyl-CoA, and NADH which indicates an already high level of energy supply.
Why is citrate synthase inhibited by ATP?
ATP is an allosteric inhibitor of citrate synthase. The effect of ATP is to increase the value of KM for acetyl CoA. Thus, as the level of ATP increases, less of this enzyme is saturated with acetyl CoA and so less citrate is formed.
Does citrate synthase require ATP?
Reaction. ATP citrate lyase is responsible for catalyzing the conversion of citrate and Coenzyme A (CoA) to acetyl-CoA and oxaloacetate, driven by hydrolysis of ATP.
Is citrate a competitive inhibitor of citrate synthase?
Citrate synthase (citrate oxaloacetate-lyase (pro-3S-CH2cOO leads to acetate-CoA), EC 4.1. Coenzyme A is inhibitory, being competitive with acetyl-CoA (Ki = 0.15 mM) and non-competitive with oxaloacetate. Citrate has no effect.
What is the total yield of ATP in TCA cycle in eukaryotic cells?
The total energy gained from the complete breakdown of one (six-carbon) molecule of glucose by glycolysis, the formation of 2 acetyl-CoA molecules, their catabolism in the citric acid cycle, and oxidative phosphorylation equals about 30 ATP molecules, in eukaryotes.
Which product is released by the citrate synthase?
Citrate synthase catalyzes the Claisen condensation between acetyl CoA and oxaloacetate to yield, after hydrolysis of the thioester bond, citrate and CoA. This reaction probably occurs via the stabilized enolate anion of acetyl CoA.
Does ATP synthase require energy?
The ATP synthase (or F1F0 ATPase and also referred to as complex V) uses the free energy of an electrochemical gradient of protons (or sodium ions) generated by the respiratory chain to synthesize ATP.
What type of inhibitor is citrate?
Citrate inhibits the reaction and is an example of product inhibition. The inhibition of citrate synthase by acetyl-CoA analogues has also been well documented and has been used to prove the existence of a single active site.
Why is ATP 36 or 38?
In eukaryotic cells, the theoretical maximum yield of ATP generated per glucose is 36 to 38, depending on how the 2 NADH generated in the cytoplasm during glycolysis enter the mitochondria and whether the resulting yield is 2 or 3 ATP per NADH.
How to inhibit citrate synthase with acetyl-CoA?
Experimental procedures Acetyl-CoA, CoA (chromatographically pure) and CoA derivatives were obtained from P-L Biochemicals, Inc. This acetyl-CoA was identical kinetically to that prepared from acetic anhydride and CoA after purification by DEAE-cellulose and Biogel P-2 chromatography as described by C. Fung and M.F. Utter (personal communication).
Which is a stronger inhibitor of citrate synthase ATP or succinyl-CoA?
Inhibition of citrate synthase by succinyl-CoA and other metabolites. The kinetic experiments reported here with purified citrate synthase from beef heart and rat liver show that succinyl-CoA is a much stronger inhibitor of citrate production than ATP, strictly competitive with acetyl-CoA and noncompetitive with respect to oxalacetate.
What are kinetic patterns of inhibition of citrate synthase?
Kinetic patterns and parameters are summarized in table 1. Care was taken to examine ATP inhibition at low concentrations of oxalacetate and under conditions where Shepherd and Garland [2] had observed an allosteric inhibition by ATP. The ATP concentration used did not contribute significantly to the ionic 36 strength.
How does Mg2 + affect the activity of citrate synthase?
Mg2+inhibits citrate synthase slightly, but relieves the inhibition caused by ATP in a complex manner. 7. At constant total adenine nucleotide concentration made up of various proportions of ATP, ADP and AMP, the activity of citrate synthase is governed by the concentration of the sum of the energy-rich phosphate bonds of ADP and ATP. 8.