24 Questions
What is the purpose of the thioester bond in the citric acid cycle?
To store energy for the cell
The carbons in CO2 originate from pyruvate in the citric acid cycle.
False
What is the function of the enzyme succinyl-CoA synthetase?
Phosphoryl transfer to GDP, producing succinate plus GTP
The energy from the thioester bond is used to produce ______________ during substrate-level phosphorylation.
GTP
What is the product of the succinate dehydrogenase reaction?
FADH2
Match the enzyme with its function:
Succinyl-CoA synthetase = Phosphoryl transfer to GDP, producing succinate plus GTP Succinate dehydrogenase = Converts succinate to fumarate, producing FADH2
GTP is not as good as ATP in the cell.
False
What is the byproduct of the citric acid cycle after two pyruvates go through the cycle?
2CO2
What is the role of the iron-sulfur center in aconitase?
Both substrate binding and catalysis
The carbon lost as CO2 in the isocitrate dehydrogenase reaction is originally from carbons in acetyl-CoA.
False
What is the function of the manganese ion in the isocitrate dehydrogenase reaction?
The manganese ion enhances the electron withdrawing power of the carbonyl, facilitating decarboxylation.
Aconitase also regulates ___________ uptake and metabolism in the cell.
iron
What is the similarity between the α-ketoglutarate dehydrogenase complex and the pyruvate dehydrogenase complex?
Both have a similar structure and function
What is the effect of inhibiting isocitrate dehydrogenase?
Increase in citrate levels
The iron-sulfur center is only involved in substrate binding.
False
Match the following enzymes with their respective cofactors:
Isocitrate dehydrogenase = Mn2+ Aconitase = Iron-sulfur center α-Ketoglutarate dehydrogenase = TPP, lipoyllysine, CoA, FAD, and NAD+ Pyruvate dehydrogenase = NAD+
Citrate synthase is activated by succinyl-CoA.
False
What is the reaction catalyzed by isocitrate dehydrogenase?
An oxidation coupled to a hydride transfer to NAD+.
What is the role of α-ketoglutarate in the citric acid cycle?
α-ketoglutarate is an important branch point for amino acid metabolism.
The Aconitase reaction is a ______________ reaction.
reversible
What is the function of succinyl-CoA in the citric acid cycle?
Inhibition of citrate synthase
The citric acid cycle and PDH complex are regulated independently.
False
Match the following enzymes with their functions:
Citrate synthase = Regulation of citrate levels Isocitrate dehydrogenase = Control of citrate levels Aconitase = Reversible dehydration reaction α-ketoglutarate dehydrogenase = Branch point for amino acid metabolism
What is the effect of accumulated citrate on phosphofructokinase-1 in glycolysis?
Inhibition
Study Notes
Iron-Sulfur Center in Aconitase
- Iron-sulfur center acts in both substrate binding and catalysis (dehydration and hydration)
- Aconitase regulates iron uptake and metabolism in the cell
Isocitrate Dehydrogenase
- Isocitrate dehydrogenase is an oxidation coupled to a hydride transfer to NAD+
- The enzyme uses a Mn2+ ion cofactor, enhancing the electron withdrawing power of the carbonyl and facilitating decarboxylation
- Carbon lost as CO2 is not originally from carbons in acetyl-CoA
α-KG Dehydrogenase Complex
- α-ketoglutarate dehydrogenase complex performs oxidative decarboxylation, splits the carbon-carbon bond, releases CO2, and reduces NAD+ to NADH
- Has a structure similar to PDH complex and also works similarly
- Has E1, E2, E3 and coenzymes TPP, lipoyllysine, CoA, FAD, and NAD+
- The energy of the oxidation is conserved in the form of a thioester bond
Similar Reactions
- Thioester bond is a high-energy bond with very negative free-energy of hydrolysis
- α-KG dehydrogenase complex and PDH complex share similarities
Origin of Carbon Atoms in CO2
- The carbons in CO2 originate from oxaloacetate, not from pyruvate
- Net complete oxidation of glucose occurs after two pyruvates go through the citric acid cycle
Succinyl-CoA Synthetase
- Succinyl-CoA synthetase performs phosphorylysis of the thioester bond, followed by phosphoryl transfer to GDP, producing succinate plus GTP
- Transfer of phosphate is mediated by His residue in the active site
- GTP is as good as ATP, with free conversion of NTPs in the cell
Succinate Dehydrogenase
- Succinate dehydrogenase converts succinate to fumarate, with reducing power transferred to FAD
- FADH2 yields 1.5 ATP
- Rate controlling enzymes: citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase
Regulation of Activity
- Regulation of activity: activated by substrate availability, inhibited by product accumulation
- Allosteric inhibition or activation by other intermediates
Other Regulation Mechanisms
- Citrate synthase is also inhibited by succinyl-CoA
- α-ketoglutarate is an important branch point for amino acid metabolism
- Succinyl-CoA communicates the flow at this branch point to the start of the cycle
- Inhibition of isocitrate dehydrogenase leads to accumulation of isocitrate, pushing the equilibrium towards citrate
- Accumulated citrate leaves mitochondria and inhibits phosphofructokinase-1 in glycolysis
This quiz covers the functions and mechanisms of enzymes involved in the citric acid cycle, including aconitase and isocitrate dehydrogenase.
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