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Section IV - The Tricarboxylic Acid Cycle

I. Tricarboxylic acid (TCA) cycle overview c) Activates acetyl-CoA carboxylase and

increases fatty acid synthesis
A. A metabolic pathway that converts acetyl-CoA
→ CO2 2. Inhibited by ATP

B. Generates NADH and FADH2 → electron B. Isocitrate dehydrogenase

transport chain → cellular energy 1. Isocitrate → α-ketoglutarate dehydrogenase
1. Also generates guanosine triphosphate 2. Produces NADH and CO2
(GTP) 3. Inhibited by ATP and NADH and activated by
C. Occurs within the mitochondria. ADP
4. Requires niacin as a cofactor and for the
production of NAD+
II. Important enzymes
C. α-ketoglutarate dehydrogenase
A. Citrate synthase
1. α-ketoglutarate → Succinyl-CoA
1. Oxaloacetate → citrate
2. Produces NADH and CO2
a) Citrate is a marker of sufficient energy
3. Inhibited by ATP, NADH, and Succinyl-CoA
b) Blocks phosphofructokinase-1 and
4. Activated by Ca2+ in skeletal muscle tissue
decreases glycolysis

Figure 2.5.5 - TCA Cycle

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5. Similar complex to pyruvate
dehydrogenase
a) Requires 5 cofactors including
thiamine (vitamin B1), lipoic acid,
CoA (vitamin B5), FAD (vitamin B2),
and NAD (vitamin B3).
b) Mnemonic: “TLC for Nancy.”
D. Succinate thiokinase
1. Succinyl-CoA → succinate
2. Produces GTP
E. Succinate dehydrogenase
1. Succinate → fumarate
2. Complex II of the ETC
3. FAD is a constituent of riboflavin
(vitamin B2) so this reaction is vitamin
B2-dependent.
F. Malate dehydrogenase
1. Malate → oxaloacetate
2. Niacin (Vitamin B3) is necessary for
the production of NAD+ and acts as a
cofactor for this enzyme.
REVIEW QUESTIONS ?
1. A 47-year-old homeless male is brought to the
ED after being found unconscious on the side
of the road. He is resuscitated and complains of
difficulty walking and remembering past events.
On exam he is ataxic and has ophthalmoplegia.
What enzyme in the TCA cycle is likely altered as
a result of this patient’s condition?
• Memory loss, ataxia, and ophthalmoplegia
are consistent with Wernicke-Korsakoff syn-
drome (caused by thiamine deficiency)
• α-ketoglutarate is the only enzyme in the
TCA cycle that requires thiamine as a cofac-
tor
2. A 24-year-old woman with a history of anorexia
nervosa presents with fissures at the corners
of her mouth and severe inflammation of her
lips. On exam she has corneal clouding due to
vascularization. What two reactions in the TCA
cycle will likely be altered as a result of this
patient’s condition?
• Inflammation at the lips and fissures at the
corners of her mouth → cheilosis
• Cheilosis and corneal vascularization are
seen in vitamin B2 deficiency
• ↓ vitamin B2 → ↓ α-ketoglutarate dehydro-
genase (α-ketoglutarate → succinyl-CoA)
• ↓ vitamin B2 → ↓ succinate dehydrogenase
(succinate → fumarate)