BCM 252

Study Unit 5:

The Citric Acid Cycle

Dr Rebamang Mosa

1
Lecture 4
LO 8

The energy of oxidations in the cycle is efficiently conserved

• Energy released
by oxidation is
conserved in the
production of:
– 3 NADH
– 1 FADH2
– 1 GTP (or ATP)

2
Fig 16-14: Products of one turn of the citric acid cycle.
LO 9

Net Result of the Citric Acid Cycle

Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2 H2O →

2CO2 + 3NADH + FADH2 + GTP + CoA + 3H+

• Net oxidation of two carbons to CO2

• Energy captured by electron transfer to NADH and FADH2
• Generates 1 GTP, which can be converted to ATP

3
LO 9
Net Results of the PDH complex reaction and the
Citric Acid Cycle
• PDH Complex:
Pyruvate + CoA-SH + NAD+ → Acetyl-CoA + NADH + H+ + CO2
• Citric acid cycle:
Acetyl-CoA + 3NAD+ + FAD + GDP + Pi + 2H2O →
2CO2 + CoA-SH + 3NADH + 3H+ + FADH2 + GTP

Overall reaction:
Pyruvate + 4NAD+ + FAD + GDP + Pi + 2H2O →
3 CO2 + 4NADH + 4H+ + FADH2 + GTP

4
LO 10
Role of the citric acid cycle in metabolism
• The CAC plays an integral role in carbohydrate, lipid
and protein metabolism
• The CAC is AMPHIBOLIC- serves in both catabolic and
anabolic processes
• The CAC is the final common pathway for the
oxidation of fuel molecules (acetyl-CoA derived from
monosaccharides, amino acids and fatty acids
catabolism)- CATABOLIC ROLE
• Cycle intermediates can be drawn off and used as the
starting material for a variety of biosynthetic products-
ANABOLIC ROLE
5
LO 10 & 11

6
Fig 16-15: Role of the citric acid in anabolism.
LO 10-12
Anaplerotic Reactions Replenish Citric Acid Cycle
Intermediates

• Several ANAPLEROTIC REACTIONS which produce 4C intermediates by

carboxylation of 3C compounds ensure that the CAC intermediates
remain almost constant (Table 16-2)

7
© 2021 Macmillan Learning
LO 12 Pyruvate carboxylase reaction
• The same reaction as for gluconeogenesis
Pyr + CO2 + ATP ⇆ OAA + ADP + Pi
• This reaction is under metabolic control
– Acetyl-CoA activates the enzyme
– If [OAA] , then the [Acetyl-CoA]  and activates the
formation of OAA, which then reacts with excess acetyl-CoA

8
Fig. 16-16: The role of biotin in the reaction
catalyzed by pyruvate carboxylase
(Watch animation on Achieve assignments)

9
LO 13
Regulation of the Citric Acid Cycle
• Regulation balances the supply of key intermediates with the
demands of energy production and biosynthetic processes
• Regulation occurs at several points- regulated at highly
thermodynamically favorable and irreversible steps
–pyruvate dehydrogenase complex
–citrate synthase
–isocitrate dehydrogenase
–α-ketoglutarate dehydrogenase complex

• General regulatory mechanism

–activated by substrate availability
–inhibited by product accumulation 10
 LO 13

Fig. 16-18: Regulation of metabolite flow from the PDH

11
complex through the CAC in mammals