Citric Acid Cycle 2
•Eight reactions and eight enzymes of the citric acid cycle
•ATP energy equivalent released in glucose metabolism
•Regulation of the citric acid cycle
•Metabolic reactions related to the citric acid cycle
Hans Idolf Krebs: Nobel Prize in Physiology or Medicine, 1953
“For his discovery of the citric acid cycle”
Fritzz Albert Lipmann: Nobel Prize in Physiology or Medicine, 1953
“For his discovery of co-enzyme A and its importance for intermediary metabolism” Citric Acid Cycle 2
The Eight Enzymes of the CAC
1. Citric Synthase The First reaction of the citric acid cycle.
Catalyzes the condensation of Acetyl Coa and oxaloacetate
The second Reaction
Catalzyes the reversible Isomerization of citrate and isocitrate with cis-acitonate as
•The hydration of the double bond of cis-aconitate could yield 4 potential stereoisomers.
•This enzyme catalyzes synthesis of only one isomer, isocitrate.
3. NAD Dependent Isocitrate Dehydrogenase
Catalyzes the oxidative decarboxylation of isocitrate to alpha -ketoglurate. This
reaction produces CO NA2H
•The CO c2rbon entered the ﬁrst stage of the citric acid cycle as a component of oxaloacetate
rather than a component of Acetyl-CoA -- NOT generated from our glucose! Citric Acid Cycle 2
4. α-Ketoglutarate Dehydrogenase
•alpha-ketoglutarate dehydrogenase is a multienzyme complex similar to the pyruvate
dehydrogenase. The vitamin thiamine is among coenzymes of the complex.
•The complex catalyzes the oxidative decarboxylation of alpha-ketoglutarate. The reaction
produces CO , 2ADH, and a high energy thioester succinyl CoA
5. Succinyl CoA Synthetase
Catalyzes the conversion of Succinyl Coa to Succinate Citric Acid Cycle 2
6. Succinate Dehydrogenase
The enzyme catalyzes the dehydrogenation of succinate to fumarate with reducing
FAD FADH 2
•The FAD prosthetic group is covalently linked to the enzyme.
Succinate dehydrogenase is the only membrane bound enzyme of the citric acid cycle.
•Upon reoxidation of FADH th2,released electrons enter the electron-transport chain of
Catalyzes the hydration of the trans double-bond of fumarate to form malate.
8. Malate Dehydrogenase
Catalyzes the ﬁnal step -- oxidation of malate to oxaloacetate.
•NAD+ is reduced to NADH and H+ is produced.
•Under standard conditions, the reaction is endergonic since oxaloacetate is consumed
immediately as it becomes produced.
The physiological concentration of oxaloacetate is very low.
• Citric Acid Cycle 2
Step Reactant Product Enzyme Notes
1) Oxidation of Acetyl-CoA Oxaloacetate Citric synthase exergonic (-32kJ/mol)
2) Reversible citrate Citrate Isocitrate Acitonase Speciﬁc to 1 of 4
3) Decarboxylation Isocitrate alpha- NAD+ CO 2s carbon from
of isocitrate ketoglutarate Dependent oxaloacetate, NOT from
isocitrate incoming Acetyl CoA
NAD+ CO 2 dehydrogenase
NADH H+ produced, but used up to
4) Oxidative a- Succinyl-CoA a-ketoglutarate Multienzyme complex
decarboxylation of ketoglutarate dehydrogenase