CITRIC ACID

CYCLE
 THE NAME

CITRIC ACID CYCLE TRICARBOXYLIC ACID CYCLE

KREBS CYCLE
After its discoverer, Hans Krebs
•Citric acid cycle • Tricarboxylic Acid
– refers to the first Cycle
molecule that forms during - for the three carboxyl
the cycle’s reaction - group on its first two
citrate, or, in its protonated intermediates.
form, citric acid.
 HOW IMPORTANT IS THE KREBS CYCLE?

• The citric cycle is a central driver of cellular respiration.

• It takes acetyl CoA –produced by the oxidation of pyruvate
and originally derived from glucose –as its starting material
and, in a series of redox reactions, harvests much of its bond
energy in the form of NADH, FADH2, and ATP molecules.
 HOW IMPORTANT IS THE KREBS CYCLE?

• The reduced electron carriers – NADH and FADH2 –

generated in the krebs cycle will pass their electron into
the electron transport chain (ETC) and, through oxidative
phosphorylation, will generate most of the ATP produced
in cellular respiration.
 LOCATION

• In eukaryotes, the citric acid cycle takes place in the matrix of

the mitochondria, just like the conversion of pyruvate to
acetyl CoA.
• In prokaryotes, these steps both take place in the cytoplasm.
The citric acid cycle is a closed loop; the last part of the
pathway reforms the molecule used in the first step. The cycle
includes eight major steps.
 STEPS OF THE KREBS CYCLE

• How, exactly , are those molecules made? We’ll

walk through the cycle steps by steps, seeing
how NAD, FADH2, ATP/GTP are produced and
where carbon dioxide molecules are released.
 STEP 1
• Acetyl CoA combines with oxaloacetate ( a four-carbon
molecule) in a reaction catalyzed by citrate synthase
• This reaction also takes a water molecule as a reactant, and
it releases a SH-CoA molecules as a product.
 CoA

H2O
Citrate synthase

CoA
 STEP 2

• Citrate is converted into its isomer, isocitrate in a

reaction catalyzed by aconitase.

Aconitase
 STEP 3
• Isocitrate is oxidized into a-ketoglutarate ( a five carbon
molecule ) in a reaction catalyzed by isocitrate
dehydrogenase.
• An NAD+ molecule is reduced to NADH + H+ in this
reaction , and
• a carbon dioxide molecule is released as a product.
 Isocitrate
dehydrogenase 2e NAD+
 STEP 4

• a-ketoglutarate is oxidized to succinyl CoA ( unstable four

carbon molecule ) in a reaction catalyzed by a-
ketoglutarate dehydrogenase.
• An NAD+ molecule is reduced to NADH + H+ in this
reaction, which also
• Takes a SH-CoA molecule as reactant.
• a carbon dioxide molecule is released as a product.
a-ketoglutarate
dehydrogenase 2e NAD+ CoA

NADH H+

CoA
 STEP 5

• CoA of succinyl CoA is replaced by a phosphate group, which

is then transferred to ADP to make ATP in some cells, GTP-
guanine diphosphate- is used instead of ADP forming GTP-
guanine triphosphate – as a product.
• The four carbon molecule produced in this step is called
succinate.
• The reaction is catalyzed by the enzyme succinyl-CoA
synthetase
 CoA

pi

GDP
ADP
Succinyl CoA synthetase
GTP
ATP
 STEP 6
• Succinate is oxidized to another four carbon molecule fumarate in a
reaction catalyzed by succinate dehydrogenase.
• FAD is reduced to FADH2 in this reaction.

Succinate 2e FAD
dehydrogenase

FADH2
 STEP 7
• This reaction requires a water molecule as a reactant.
• Fumarate is converted to malate in a reaction catalyzed by the enzyme
fumarase.

fumarase H2O
 STEP 8

• Malate is oxidized to oxaloacetate- the stating four carbon

compound catalyzed by malate dehydrogenase.
• This reaction reduces an NAD+ molecule to NADH + H+
Malate dehydrogenase
2e NAD+

NADH H+
 PRODUCTS
• Reminder: Everything is always multiplied by two as, two
(2) acetyl CoA were produced from pyruvate oxidation.
• 4 H2O were used
• 2 ATP produced from step 5
• 4 CO2 were released
• 6 NADH were produced
• 2 FADH2 were produced
• Regenerated two(2) carbon molecule OXALOACETATE