Krebs Cycle

(Tricarboxylic acidcycle(TCA),
citric acid cycle)
IKRAM ULLAH
14

Citric Acid cycle

OBJECTIVES
Brief Overview
Pyruvate Dehydrogenase Complex (PDC)
Reactions of TCA cycle or CAC
Amphibolic nature of TCA cycle
Regulation of TCA cycle

OVERVIEW
Cyclic process.
Enzymes are located in Mitochondrial Matrix.
Whole process is aerobic.
pyruvate dehydrogenase and TCA cycle reactions take place in mitochondria where
oxygen is utilized to generate ATP by oxydative phosphorylation.

Overall goal
Makes ATP
Makes NADH
Makes FADH2
Requires some Acetyl CoA to run

In Cytosol

In Mitochondria

Reaction of pyruvate dehydrogenase complex (PDC)

Mg

Reaction of TCA cycle:

Enzymes
Acetyl CoA
12ATP

2CO
2

REACTIONS OF TCA CYCLE

Citrate Synthase Reaction (First)
O

H3C

SCoA

acetyl CoA

O
C
C O
CH2
C
O

H2O

CoASH
HO

citrate synthase
O

C
CH2 O
C C O
CH2
C
O

oxaloacetate

citrate

Irreversable
A molecule of H2O is required
No ATP is required
No Oxidation or decarboxylation.

Aconitase Reaction
O

HO

C
CH2
C C
CH2
C

O
O

HO

aconitase

citrate

C
CH
HC C
CH2
C
O

O
O

isocitrate

Forms isocitrate
Hydroxyl moved and changed from tertiary to secondary
(can be oxidized)

1st dehydretion to form cis Aconitate

The rehydration to form isocitrate

Isocitrate Dehydrogenase
O
HO

C
CH
HC C
CH2
C
O

NAD

NADH

CO2

isocitrate

C
C O
CH2
CH2
C

isocitrate dehydrogenase

alpha ketoglutarate

All dehydrogenase reactions make NADH or FADH2

Oxidative decarboxylation

-ketoglutarate dehydrogenase
O

C
C O
CH2
CH2

SCoA

CoASH

CO2

NAD

NADH

C
O

alpha ketoglutarate

alpha ketoglutarate

C
CH2
CH2
C
O

dehydrogenase

Same as pyruvate dehydrogenase reaction

Formation of thioester

succinyl CoA

Succinyl CoA synthetase

SCoA

C
CH2
CH2
C
O

succinyl CoA

O
GDP

GTP

CoASH

O
C
CH2
CH2

succinyl CoA
synthetase

succinate

Succinate dehydrogenase
O

C
CH2

CH2
C
O
O
succinate

Dehydrogenation
Uses FAD

FAD

C
C

FADH2
H

succinyl CoA
dehydrogenase

C
C

fumarate

Fumarase
O

C
C
H
O

C
C

H2O
H
fumarase

fumarate

O
C
HC OH
CH2
C
O

malate

Addition of water to a double bond

Malate Dehydrogenase
O

O
C
HC OH
CH2
C
O

malate

O
NADH

NAD

malate

dehydrogenase

O
C
C O
CH2
C
O

oxaloacetate

Makes NADH
Regenerates oxaloacetate for another round

Net From Krebs

Oxidative process
3 NADH
FADH2
GTP

X 2 per glucose
6 NADH
2 FADH2
2 GTP

All ultimately turned into ATP (ETC)

Total Energy per glucose

Cytosol
Glycolysis
2 NADH
2 ATP

Mitochondrion
Pyruvate dehydrogenase
2 NADH

Krebs
6 NADH
2 FADH2
2 GTP

The amphibolic nature of Citric acid

cycle:
Cycle Has dual role.

Catabolic Role
The Acetyl CoA produced from
metabolism of carbohydrates , Proteins
and lipids oxidized in this cycle to produce
CO 2 , H 2O and energy as ATP .

Enzymes
Acetyl CoA
12ATP

2CO2

Anabolic Role
Intermediate of TCA cycle are utilized for
Synthesis of Various compounds :
Synthesis of non essential amino acids
Haem Synthesis
Fatty acids and cholestrol synthesis

Regulation of CAC:
Rate controlling enzymes:
Citrate synthatase
Isocitrate dehydrogenase
-keoglutaratedehydrogenase

 These enzymes are inhibited by ATP ,

NADH+H ,FADH+H and succinyl CoA.
While activated by ADP , Ca , NAD and
FAD.
NOTE:
Hormones doesnt regulate the TCA Cycle directly.