Krebs Cycle/

Citric Acid Cycle/

Tricarboxylic Acid Cycle.
FST 1022
Essentials Of Biocehmistry
Presented By: Nida Iqbal Khan
 Step 01
Formation of Citrate
 In the first step of the citric acid cycle, acetyl CoA joins with a
four-carbon molecule, oxaloacetate, releasing the CoA group
and forming a six-carbon molecule called citrate.
 The first reaction of the citric acid cycle is catalyzed by the
enzyme citrate synthase.
 Oxaloacetate is the final metabolite of the Kreb Cycle and it
joins again to start the cycle over again, hence the name Kreb's
Cycle.
 Step 02
 Formation of Isocitrate
 In step two, citrate loses one water molecule and gains another
as citrate is converted into its isomer, Isocitrate by an
enzyme acontinase.
 This is actually a two-step process, involving first the removal
and then the addition of a water molecule, which is why the
citric acid cycle is sometimes described as having nine steps—
rather than the eight listed here.
 Step 03
 Oxidation of Isocitrate to α-Ketoglutarate: 
 In step three, isocitrate is oxidized, producing a five-carbon
molecule, α-ketoglutarate, along with a molecule of CO2 and
two electrons, which reduce NAD+ to NADH.
 The enzyme catalyzing this step, isocitrate dehydrogenase, is
important in regulating the speed of the citric acid cycle.
 Step 04
 Oxidation of α-Ketoglutarate to Succinyl-CoA:
 Alpha-ketoglutarate loses a carbon dioxide molecule and
coenzyme A is added in its place.
 The decarboxylation occurs with the help of NAD, which is
converted to NADH. The enzyme that catalyzes this reaction is
alpha-ketoglutarate dehydrogenase.
 Step 04
 This step involves a highly-developed complex of 24 enzymes.
Labeled here α–ketoglutarate dehydrogenase,
 This complex transfers also electrons to NAD+ producing
NADH,
 Removes another carbon atom as carbon dioxide
(transforming the substrate from a 5-carbon to a 4-carbon
molecule), and relinks the Coenzyme A to the substrate.
 Step 05
 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. 
 Step 05
  In step five, the CoA of succinyl CoA is replaced by a
phosphate group, which is then transferred to ADP to make
ATP.
 The enzyme succinyl-CoA synthase catalyzes this reaction of
the citric acid cycle. CoA is removed from succinyl-CoA to
produce succinate.
 Step 06
 Oxidation of Succinate to Fumarate:
 Succinate is oxidized to fumarate. During this oxidation,The
enzyme succinate dehydrogenase catalyzes the removal of two
hydrogens from succinate.
 Two hydrogen atoms are transferred to FAD, Flavin adenine
dinucleotide producing FADH2 which is then transferred to
power the electron transport chain.
 Step 07
 Hydration of Fumarate to Malate:
 In this reaction, the enzyme fumarase catalyzes the addition of
a water molecule to the fumarate in the form of an –OH group
to yield the molecule malate.
 Step 08
 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+.
 Products Of TCA Cycle
 In a single turn of the cycle,
 Two carbons enter from acetyl coa, and two molecules of carbon
dioxide are released;
 Three molecules of NADH and one molecule of FADH2​ are

generated; and
 One molecule of ATP or GTP is produced.
 These figures are for one turn of the cycle, corresponding to one

molecule of acetyl CoA.

 Each glucose produces two acetyl CoA molecules, so we need to

multiply these numbers by 2 if we

 Oxidation of pyruvate: 2 CO , 2 NADH, 2 acetyl (2 carbon molecule)
2
 Products of the citric acid cycle: 4 CO , 6 NADH, 2 FADH , 2 ATP
2 2
Summary
 Refrences
 Advances in Food Biochemistry by Fatih
Yildiz 2009. CRC press
