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KREB CYCLE
OR
CITRIC ACID CYCLE
OR
TRICARBOXYLIC ACID CYCLE
(TCA)
.
 Involves
oxidation of acetyl CoA to CO2 AND
H2O.
 65-70 percentage ATP synthesized .
 Final common oxidative pathway for
carbohydrates, fats and amino acid.
 Connecting all individual metabolic pathways.
 Important metabolic pathway for energy supply
to body.
 Cyclic process.
 Oxaloacetate is considered to play catalytic role .
CIRIC ACID ENZYMES ARE FOUND IN
MITOCHONDRIAL MATRIX

Substrate have to flow across the outer and inner
part of mitochondria.
PRODUCTION OF ACETYL Co-A

Pyruvate dehydrogenase complex: it is multienzyme containing 3 enzymes associated together
non-covalently.
E-1:Pyruvate dehydrogenase
E-2:Dihydrolipoyl transacetylase
E-3:Dihydrolipoyl dehydrogenase
REACTIONS OF CITRIC
CYCLE: 8 reactions

citrate synthase

Aconitase

Iso-citrate
dehydrogenase
a ketoglutarate
dehydrogenase

Succinyl- CoenzymeA
synthetase


Succinate dehyrogenase

Fumerase

Malate dehydrogenase
.
CONDENSATION
.

Involves condensation of acetyl-CoA with oxaloacetate ,
catalyzed by citrate synthase.
DEHYDRATION
HYDRATION
OXIDATIVE DECARBOXYLATION
.
•
Involves oxidation of Isocitrate to a- ketoglutarate.
.
OXIDATIVE DECARBOXYLATION
•
Involves oxidation of a-ketoglutarate to Succinyl-CoA.
SUBSTRATE LEVEL PHOSPHORYLATION
.
HYDRATION
.
DEHYDROGENATION
REGULATION
Brought either by enzymes
or level of ADP.
 3 Enzymes regulated TCA:1. citrate synthase: inhibited
by ATP , NAD, acetyl CoA
and succinyl CoA.
2. Isocitrate dehydrogenase:
activated by ADP and
inhibited by ATP and NADH.
3. alfa-ketoglutarate
dehydrogenase: inhibited by
succinyl CoA and NADH.
4. Availability of ADP

Amphibolic nature
Kreb cycle is both catabolic and anabolic in nature.
Hence regarded as Amphibolic.
 Involved in gluconeogenesis , transamination and
deamination.
 Also provide precursors for many biosynthetic
pathway. For ex.
1. alfa-ketoglutarate and oxaloacetate : serve as
precursor of amino acids, aspartate and glutamate by
simple transamination and required for synthesis of
non-essential amino acids ,purines and pyrimidines.
2. succinyl CoA : used for synthesis of heme.

Anaplerotic
reactions

The reactions concerned to fill up the intermediates of citric acid
cycle are Anaplerotic reactions or anaplerosis.
-
1.Pyruvate + HCO3
+ ATP pyruvate carboxylase oxaloacetate +ADP+ Pi
pyruvate carboxylase : catalyses conversion of pyruvate to
oxaloacetate .
take place in mammalian kidney and liver.
2. PEP + CO2 + GDP PEP carboxykinase oxaloacetate + GTP
take place in heart and skeletal muscle.
-
3. PEP + HCO3
PEP carboxylase
oxaloacetate + Pi
take place in higher plants , yeast and bacteria.
-
4. Pyruvate + HCO3 + NAD(P)H malic enzyme malate + NAD(P)+
widely distributed in eukaryotes and prokaryotes.
GLYOXYLATE
CYCLE
Plants and many organisms are equipped
with glyoxylate cycle- to convert fat into
carbohydrates.
oThe animals like man cannot carry out the
net synthesis of carbohydrates from fat.
oActive in the germinating seeds of some
plants .
o take place in glyoxysomes which is
specialized
cellular organelles where fatty
.
acid synthesis is operative.
o
oEach turn of this cycle consumes 2 molecules of acetyl-CoA and
produces one molecule of succinate.
REGULATION OF GLYOXYLATE AND
CITRIC ACID CYCLE
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