BATANGAS STATE UNIVERSITY

Gov. Pablo Borbon Campus II

Batangas City
COLLEGE OF ENGINEERING, ARCHITECTURE AND FINE ARTS
Chemical and Food Engineering Department
Alangilan, Batangas City

ChE-419: INTRODUCTION TO BIOTECHNOLOGY

THE KREBS CYCLE
Atienza, Mark Agustin M.
Satira, Andrea A.
ChE-4102

June 24, 2015

The Krebs cycle

The Krebs cycle also known as the tricarboxylic acid (TCA) cycle or citric acid cycle
is a series of chemical reactions used by all aerobic organisms to generate energy
through the oxidation of acetate derived from carbohydrates, fats and proteins into
carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP). In
addition, the cycle provides precursors of certain amino acids as well as the
reducing agent NADH that is used in numerous other biochemical reactions. Its
central importance to many biochemical pathways suggests that it was one of the
earliest established components of cellular metabolism and may have originated
abiogenically.
In eukaryotic cells, the citric acid cycle occurs in
the matrix of the mitochondrion. In prokaryotic
cells, such as bacteria which lack mitochondria,
the TCA reaction sequence is performed in the
cytosol with the proton gradient for ATP
production being across the cell's surface
(plasma membrane) rather than the inner
membrane of the mitochondrion.
Several of the components and reactions of the
citric acid cycle were established in the 1930s
by the research of the Nobel laureate Albert
Szent-Gyrgyi, for which he received the Nobel
Prize in 1937 for his discoveries pertaining to
fumaric acid, a key component of the cycle. The
citric acid cycle itself was finally identified in
1937 by Hans Adolf Krebs while at the
University of Sheffield, for which he received
the Nobel Prize for Physiology or Medicine in 1953.
Organisms derive the majority of their energy from the Kreb's Cycle, also known as
the TCA cycle. The Kreb's Cycle is an aerobic process consisting of eight definite
steps. In order to enter the Kreb's Cycle pyruvate must first be converted into
Acetyl-CoA by pyruvate dehydrogenase complex found in the mitochondria.
In reality, the Krebs cycle is not only part of the pathway for the breakdown of
glucose but also for the breakdown of all metabolites, including other sugars, amino
acids and fatty acids. Each of these groups of molecules has a pathway that leads
into the Krebs cycle. For example, carbohydrates are converted into acetyl CoA by
the process of glycolysis while fatty acids are converted into acetyl CoA by the beta
oxidation pathway. In each case, the molecules are converted into products that
enter the Krebs cycle. In addition, intermediates from the Krebs cycle can go the

other direction and be used to synthesize molecules such as amino acids and fatty
acids. For example, acetyl CoA can be used to synthesize fatty acids.

Illustration of Krebs cycle

Steps in Krebs cycle

In order for pyruvate from glycolysis to enter the Kreb's Cycle it must first be
converted into acetyl-CoA by the pyruvate dehydrogenase complex which is an
oxidative process wherein NADH and CO2 are formed. Another source of acetyl-CoA
is beta oxidation of fatty acids.
Items to note about this reaction:
Pyruvate is the product of glycolysis, thus it comes from glucose. It
may also come from some amino acids.
The reaction occurs in the mitochondrion.
This is an oxidation reaction which results in the formation of an NADH.
One carbon is removed from pyruvate in the form of carbon dioxide
(note the yellow carbon in the above figure). This leaves just two
carbons remaining from pyruvate.
The addition of the coenzyme A to the acetate (see red in the above
figure) acts to conserve the energy released from the reaction and to
energize the acetate.

I.

Acetyl-CoA enters thE Kreb Cycle when it is joined to oxaloacetate by citrate

synthase to produce citrate. This process requires the input of water.
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. This is known as the
committed step.

Items to note about this reaction:

This is the first reaction of the Krebs cycle.
Acetyl CoA is the actual reactant of the entire Krebs cycle and
represents the only carbons that are actually oxidized to carbon
dioxide during the cycle and they are the only carbons that enter the
Krebs cycle from the breakdown of nutrients.
This is not an oxidation thus no NADH is formed.
OAA is not oxidized during the cycle but is regenerated so that the
cycle can continue.

II.

Citrate is then converted into isocitrate by the enzyme aconitase. This is

accomplished by the removal and addition of water to yield an isomer.

III.

Isocitrate is converted into alpha-ketogluterate by isocitrate dehydrogenase.

The byproducts of which are NADH and CO2.

Items to note about this reaction:

It is an oxidation with the production of an NADH which is storing
energy and electrons.
Carbon dioxide is released so that of the three carbons originally in the
pyruvate, two have been released as carbon dioxide due to oxidation
reactions.
Alpha ketoglutarate is a common entrance point for some amino acids
into the Krebs Cycle. Thus if the cell needs to utilize amino acids as an
energy source, some amino acids ultimately are converted into alpha
ketoglutarate and enter the Krebs Cycle.

IV.

Apha-ketogluterate is then converted into succynl-CoA by alpha-ketogluterate

dehydrogenase. NADH and CO2 are once again produced.

Items to note about this reaction:

It is an oxidation reaction in which an NADH is made.
This is the last reaction of the cycle in which a carbon dioxide is
removed as we have now accounted for all carbons entering the cycle
through pyruvate.
The addition of the coenzyme A to the acetate (see red in the above
figure) acts to conserve the energy released from the reaction and to
energize the succinate.
The cycle must use the remaining steps to convert the succinyl CoA
into oxaloacetate and complete the cycle.

V.

Succynl-CoA is then converted into succinate by succynl-CoA synthetase

which yields one ATP per succynl-CoA.

Items to note about this reaction:

The removal of the CoA from the succinate releases the stored energy.
This energy is used to phosphorylate ADP and form ATP (of course, it is

really GDP that is being phosphylated to GTP - we just pretend that ATP
is being formed!)
This is the first and only reaction of the Krebs Cycle that produces an
ATP. Because the phosphorylation of ADP occurs as a part of the
reaction of the substrate, this is referred to as substrate level
phosphorylation of ADP.
This reaction is not an oxidation reaction so there is no production of
NADH during the reaction.

VI.

Succinate coNverts into fumerate by way of the enzyme succinate

dehydrogenase and [FAD] is reduced to [FADH2] which is a prosthetic group
of succinate dehydrogenase. Succinate dehydrogenase is a direct part of the
ETC. It is also known as electron carrier II.

Items to note about this reaction:

It is an oxidation that results in the formation of an FADH (not an
NADH).
The oxidation of FADH does release as much energy as does the
oxidation of NADH.

VII.

Fumerate is then converted to malate by hydration with the use of fumerase.

VIII.

Malate is converted into oxaloacetate by malate dehydrogenase the

byproducts of which are NADH.

Items to note about this reaction:

This is an oxidation reaction that produces an NADH.
Considered the last reaction of the cycle, it is important as it
regenerates OAA so that the cycle can continue.