KREBS 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 4-2 > 2 CO2 + CoA + 3 NADH+ +
FADH+ + ATP
Reaction 1: Formation of Citrate
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
transformation
molecule.
yields
This
the
molecule isocitrate.
The first reaction of the cycle is the
condensation
of acetyl-
CoA with oxaloacetate to
form citrate,
Reaction 3: Oxidation of Isocitrate to
-Ketoglutarate
catalyzed by citrate synthase.
Once oxaloacetate is joined with acetylCoA, a water molecule attacks the acetyl
leading to the release of coenzyme A from
the complex.
Reaction 2: Formation of Isocitrate
In this step, isocitrate dehydrogenase
catalyzes
oxidative
decarboxylation
of isocitrate to form -ketoglutarate.
In the reaction, generation of NADH from
NAD is seen. The enzyme isocitrate
dehydrogenasecatalyzes the oxidation of
the OH group at the 4 position of
isocitrate to yield an intermediate which
The citrate is rearranged to form an
then has a carbon dioxide molecule
isomeric
removed
form, isocitrate by
enzyme acontinase.
an
from
ketoglutarate.
it
to
yield alpha-
CoA is removed from succinyl-CoA to
produce succinate.
The energy released is used to make
guanosine
Reaction
4:
Oxidation
of
Ketoglutarate to Succinyl-CoA
triphosphate
(GTP)
from
guanosine diphosphate (GDP) and Pi by
substrate-level phosphorylation. GTP can
then
be
used
to
make
ATP. The
enzymesuccinyl-CoA
synthase catalyzes this reaction of the
citric
acid
cycle.
Reaction 6: Oxidation of Succinate to
Fumarate
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
isalpha-ketoglutarate
dehydrogenase.
Succinate is oxidized to fumarate.
During this oxidation, FAD is reduced to
Reaction 5: Conversion of SuccinylCoA to Succinate
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 Lmalate 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.
Reviewing the whole process, the Krebs
cycle primarily transforms the acetyl group
and water, into carbon dioxide and
energized forms of the other reactants.
Reaction 8: Oxidation of Malate to
Oxaloacetate
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.
Malate is
oxidized
produce oxaloacetate,
compound
of
the
to
the
citric
2.
takes
starting
part
in
like
succinyl
CoA
the
formation
of
chlorophyll.
acid
cycle by malate dehydrogenase. During
Intermediate
3.
Amino Acids are formed from -
this oxidation, NAD+ is reduced to NADH
Ketoglutaric acid, pyruvic acids and
+ H+.
oxaloacetic acid.
4.
Krebs cycle (citric Acid cycle)
releases
plenty
of
energy
(ATP)
required for various metabolic activities
ATP Generation
of cell.
Total ATP = 12 ATP
3 NAD+ = 9 ATP
1 FAD = 2 ATP
1 ATP = 1 ATP
5.
By this cycle, carbon skeleton are
got, which are used in process of
growth and for maintaining the cells.
