Tricarboxylic Acid Cycle

Dr Imran Siddiqui (MBBS, MPhil)

College of Medicine
King Saud Bin Abdulaziz University for Health
Sciences
 Fate of Pyruvate
Glucose
glycolysis
Anaerobic 2 Pyruvate Anaerobic
2CO2 aerobic

2 Ethanol + 2 CO2 2 Lactate

(in yeast) 2 Acetyl CoA (in contracting
muscle, RBCs)
citric acid cycle

4 CO2 + 4 H2O
(animal, plant, and microorganisms under aerobic conditions)
 Citric Acid Cycle
and
Oxidative
Anaerobic
Phosphorylation
Glycolysis gives only a
Aerobic fraction of the ATP
available from glucose.
Complete oxidation to CO2
takes place in the citric
acid cycle.

In oxidative
phosphorylation, electrons
removed in oxidation,
reduce O2 and synthesize
large amounts of ATP.
 Formation of acetyl CoA
Under aerobic conditions, pyruvate is not reduced to
lactate, but decarboxylated to acetate, which links to
Coenzyme A.
• Catalyzed by pyruvate dehydrogenase
(PDH) multienzyme complex consisting of 3
catalytic subunits and several cofactors.
• PDH is directly inhibited by NADH, acetyl
CoA, and ATP.
• PDH exists in phosphorylated (inactive) and
dephosphorylated (active) states. Insulin
stimulates dephosphorylation.
•Deficiency of PDH causes Congenital Lactic
Acidosis resulting psychomotor retardation
to death
Protein kinase
PDH PDH-PO4
(active) Phosphatase (inactive)

Insulin +
Regulation of Pyruvate Dehydrogenase
 Overview of citric acid cycle
(TCA or Krebs cycle)
Oxidation of two-carbon units, producing 2 CO2, 1 GTP, and
high-energy electrons in the form of NADH and FADH2.

citrate

Mitochondrial
matrix
 Pyruvate
dehydrogenase
Citrate synthase Aconitase

Pyruvate Citrate

H2O
NAD NADH Aconitase
CO2 cis-Aconitate
Oxaloacetate
Malate H2O
dehydrogenase NADH

NAD Isocitrate

Malate
Citric acid cycle Isocitrate
dehydrogenase

Fumarase
For reference only
H2O
NAD
NADH Oxalosuccinate
FADH2 CO2
Fumarate NADH
FAD CO2 NAD Isocitrate
dehydrogenase
Succinate
GTP GDP
dehydrogenase

α -Ketoglutarate
Succinate

Succinyl-CoA α -Ketoglutarate
synthetase dehydrogenase
Succinyl-CoA
Overview of control points for
the citric acid cycle
 Energy-generating capacity of glycolysis and the citric acid cycle
A total of ~38 ATP molecules
are formed from 1 glucose
under aerobic conditions
Every NADH that is produced
needs to be re-oxidized to NAD+
Glycolysis
This re-oxidation occurs
by transferring the electrons
from NADH and FADH2 into
the electron transport chain

Electron transport chain results in the

electrons going into O2 to
produce H2O and oxidative
phosphorylation uses the energy
accumulated by the electron transport
chain to drive ATP synthesis
For every 1 NADH ~ 3 ATP are made Citric
Acid
For every 1 FADH2 ~ 2 ATP are made
Cycle
 Animation
• No. 1
• No. 2