Krebs (Citric Acid) Cycle
It is also known as TriCarboxylic Acid (TCA) cycle. In prokaryotic cells, the
citric acid cycle occurs in the cytoplasm; in eukaryotic cells, the citric acid
cycle takes place in the matrix of the mitochondria.
The cycle was first elucidated by scientist “Sir Hans Adolf Krebs” (1900 to
1981). He shared the Nobel Prize for physiology and Medicine in 1953 with
Fritz Albert Lipmann, the father of ATP cycle.
The process oxidises glucose derivatives, fatty acids and amino acids to
carbon dioxide (CO2) through a series of enzyme controlled steps. The
purpose of the Krebs Cycle is to collect (eight) high-energy electrons from
these fuels by oxidising them, which are transported by activated carriers
NADH and FADH2 to the electron transport chain. The Krebs Cycle is also the
source for the precursors of many other molecules, and is therefore an
amphibolic pathway (meaning it is both anabolic and catabolic).
The Net Equation
acetyl CoA + 3 NAD + FAD + ADP + HPO —————> 2 CO + CoA + 3
4
-2
2
NADH + FADH + ATP
+ +
Reaction 1: Formation of Citrate
The first reaction of the cycle is the condensation of acetyl-
CoA with oxaloacetate to form citrate, catalyzed by citrate synthase.
Once oxaloacetate is joined with acetyl-CoA, a water molecule attacks the
acetyl leading to the release of coenzyme A from the complex.
Reaction 2: Formation of Isocitrate
The citrate is rearranged to form an isomeric form, isocitrate by an
enzyme acontinase.
In this reaction, a water molecule is removed from the citric acid and then
put back on in another location. The overall effect of this conversion is that the
–OH group is moved from the 3′ to the 4′ position on the molecule. This
transformation yields the molecule isocitrate.
Reaction 3: Oxidation of Isocitrate to α-
Ketoglutarate
In this step, isocitrate dehydrogenase catalyzes oxidative decarboxylation
of isocitrate to form α-ketoglutarate.
In the reaction, generation of NADH from NAD is seen. The
enzyme isocitrate dehydrogenase catalyzes the oxidation of the –OH group
at the 4′ position of isocitrate to yield an intermediate which then has a carbon
dioxide molecule removed from it to yield alpha-ketoglutarate.
Reaction 4: Oxidation of α-Ketoglutarate to
Succinyl-CoA
Alpha-ketoglutarate is oxidized, carbon dioxide is removed, and coenzyme A
is added to form the 4-carbon compound succinyl-CoA.
During this oxidation, NAD+ is reduced to NADH + H+. The enzyme that
catalyzes this reaction is alpha-ketoglutarate dehydrogenase.
Reaction 5: Conversion of Succinyl-CoA to
Succinate
CoA is removed from succinyl-CoA to produce succinate.
The energy released is used to make guanosine triphosphate (GTP) from
guanosine diphosphate (GDP) and Pi by substrate-level phosphorylation. GTP
can then be used to make ATP. The enzyme succinyl-CoA
synthase catalyzes this reaction of the citric acid cycle.
Reaction 6: Oxidation of Succinate to
Fumarate
Succinate is oxidized to fumarate.
During this oxidation, FAD is reduced to FADH2. The enzyme succinate
dehydrogenase catalyzes the removal of two hydrogens from succinate.
Reaction 7: Hydration of Fumarate to Malate
The reversible hydration of fumarate to L-malate is catalyzed by fumarase
(fumarate hydratase).
Fumarase continues the rearrangement process by
adding Hydrogen and Oxygen back into the substrate that had been
previously removed.
Reaction 8: Oxidation of Malate to
Oxaloacetate
Malate is oxidized to produce oxaloacetate, the starting compound of the
citric acid cycle by malate dehydrogenase. During this oxidation, NAD+ is
reduced to NADH + H+.
ATP Generation
Total ATP = 12 ATP
3 NAD+ = 9 ATP
1 FAD = 2 ATP
1 ATP = 1 ATP
Reviewing the whole process, the Krebs cycle primarily transforms the acetyl
group and water, into carbon dioxide and energized forms of the other
reactants.
Significance of Krebs Cycle
1. Intermediate compounds formed during Krebs cycle are used for the
synthesis of biomolecules like amino acids, nucleotides, chlorophyll,
cytochromes and fats etc.
2. Intermediate like succinyl CoA takes part in the formation of chlorophyll.
3. Amino Acids are formed from α- Ketoglutaric acid, pyruvic acids and
oxaloacetic acid.
4. Krebs cycle (citric Acid cycle) releases plenty of energy (ATP) required
for various metabolic activities of cell.
5. By this cycle, carbon skeleton are got, which are used in process of
growth and for maintaining the cells.
