Krebs Cycle
Krebs Cycle
Cycle
Course: Principles
of Biochemistry
By;
M. Sheraz Yasin
Lecturer,
Institute of Biochemistry and Biotechnology,
University of Veterinary and Animal Sciences, Lahore.
Synthesis of
glycogen
Glucose Pentose phosphate
pathway
Degradation of
glycogen
Glycolysis Gluconeogenesis
Tricarboxylic
reactions was critical to the
understanding of cell
Acid Cycle metabolism and earned him
the 1953 Nobel Prize for
Krebs Cycle Physiology or Medicine.
In
eukaryotes
the reactions
of the citric
acid cycle
take place
inside
mitochondria
An Overview of the Citric Acid Cycle
A four-carbon oxaloacetate condenses with a
two-carbon acetyl unit to yield a six-carbon
citrate.
An isomer of citrate is oxidatively
decarboxylated and five-carbon -
ketoglutarate is formed.
-ketoglutarate is oxidatively
decarboxylated to yield a four-carbon
succinate.
Oxaloacetate is then regenerated from
succinate.
Two carbon atoms (acetyl CoA) enter the
cycle and two carbon atoms leave the cycle
in the form of two molecules of carbon
dioxide.
Three hydride ions (six electrons) are
transferred to three molecules of NAD+, one The function of the citric acid
pair of hydrogen atoms (two electrons) is cycle is the harvesting of high-
transferred to one molecule of FAD. energy electrons from acetyl CoA.
1. Citrate Synthase
• Citrate formed from acetyl CoA and oxaloacetate
• Only cycle reaction with C-C bond formation
• Addition of C2 unit (acetyl) to the keto double bond
of C4 acid, oxaloacetate, to produce C6 compound,
citrate
citrate synthase
2. Aconitase
• Elimination of H2O from citrate to form C=C bond
of cis-aconitate
• Stereospecific addition of H2O to cis-aconitate to
form isocitrate
aconitase aconitase
3. Isocitrate Dehydrogenase
• Oxidative decarboxylation of isocitrate to
a-ketoglutarate (a metabolically irreversible reaction)
• One of four oxidation-reduction reactions of the cycle
• Hydride ion from the C-2 of isocitrate is transferred to
NAD+ to form NADH
• Oxalosuccinate is decarboxylated to a-ketoglutarate
-ketoglutarate
dehydrogenase
5. Succinyl-CoA Synthetase
• Free energy in thioester bond of succinyl CoA is
conserved as GTP or ATP in higher animals (or ATP
in plants, some bacteria)
• Substrate level phosphorylation reaction
+ HS-
Succinyl-CoA
Synthetase
Succinate
Dehydrogenase
7. Fumarase
• Stereospecific trans addition of water to the
double bond of fumarate to form L-malate
• Only the L isomer of malate is formed
Fumarase
8. Malate Dehydrogenase
Malate is oxidized to form oxaloacetate.
Malate
Dehydrogenase
Stoichiometry of the Citric Acid Cycle
Two carbon atoms enter the
cycle in the form of acetyl
CoA.
Two carbon atoms leave the
cycle in the form of CO2 .
Four pairs of hydrogen
atoms leave the cycle in four
oxidation reactions (three
molecules of NAD+ one
molecule of FAD are reduced).
One molecule of GTP,
is formed.
Two molecules of water are
consumed.
9 ATP (2.5 ATP per NADH, and 1.5
ATP per FADH2) are produced during
oxidative phosphorylation.
1 ATP is directly formed in the
citric acid cycle.
1 acetyl CoA generates
approximately 10 molecules of ATP.
Functions of the Citric Acid Cycle