CITRIC ACID

CYLE
Agsalog, Celine
Joy
Santos, Nel Joy
Soto, Sharlene
Megan
Rondares,
Christian
Daybelyn
pagtulingan

Citric Acid Cycle

It is called the Krebs cycle or the
tricarboxylic cycle and is the hub of
the metabolic system. It accounts for
the majority of carbohydrate, fatty acid
and amino acid oxidation.
It is a series of enzyme-catalyzed
chemical reactions that form a key part
of aerobic respiration in cells. The
greatly simplified cycle below starts
with pyruvate, which is the end product
of gylcolysis, the first step of all types

History
By 1930 it was established that the addition

of lactate, acetate succinate, malate, ketoglutaric acid (dicarboxylic acids) and

citrate and isocitrate (tricarboxylic acids) when
added to muscle mince that they stimulated
oxygen consumption and release of CO2

1935 Albert Szent-Gyorgyi showed that:

 1936 Martius and Knoop showed that

pyruvate and oxaloacetate could form
citrate non-enzymatically by the
addition of peroxide under basic
conditions.

Carl Martius and Franz Knoop showed:

 Krebs showed that succinate is formed

from fumarate, malate or oxaloacetate.
This is interesting since it was shown
that the other way worked as well!!
Pyruvate can form citrate enzymatically

The interconversion rates of the

intermediates was fast enough to support
respiration rates.

Overview of the citric

acid cycle
In eukaryotes, the citric acid cycle takes place
in the matrix of the mitochondria, just like the
conversion of pyruvate to acetylCoA.
In prokaryotes, the steps are take place in the
cytoplasm.

PYRUVATE DEHYDROGENASE
DIHYDROLIPOYL
TRANSACETATE
DIHYDROLIPOYL
DEHYDROGENASE

ACETYLCOA

CITRATE

COMPOUND
BREAKDOWN

OXALOACETA
TE

CIS ACONITATE
NAD
H

MALATE

ISO CITRATE
NAD
H

FUMARATE

FAD

KETOGLUTARATE
AT
P

SUCCINATE

NAD
H

C
SUCCINYLCOA

ENZYME BREAKDOWN

eactions of Citric Acid Cycle

1. Citrate synthase: Formation of Citroyl CoA intermediate.
Binding of Oxaloacetate to the enzyme results in conformational change which
facilitates the binding of the next substrate, the acetyl Coenzyme A. There is a
further conformational change which leads to formation of products. This
mechanism of reaction is referred as induced fit model.

2. Aconitase: This enzyme catalyses the isomerization reaction by

removing and then adding back the water ( H and OH ) to cis-aconitate
in at different positions. Isocitrate is consumed rapidly by the next
step thus deriving the reaction in forward direction.

3. Isocitrate dehydrogenase: There are two isoforms of this enzyme, one

uses NAD+ and other uses NADP+ as electron acceptor.

4. -Ketoglutarate dehydrogenase: This is a complex of different

enzymatic activities similar to the pyruvate dyhdogenase complex.

5. Succinyl CoA synthatse: Sccinyl CoA, like Acetyl CoA has a

thioester bond with very negative free energy of hydrolysis. In this
reaction, the hydrolysis of the thioester bond leads to the formation
of phosphoester bond with inorganic phosphate. This phosphate is
transferred to Histidine residue of the enzyme and this high energy,
unstable phosphate is finally transferred to GDP resulting in the
generation of GTP.

6. Succinate Dehydrogenase: Oxidation of succinate to fumarate. This

is the only citric acid cycle enzyme that is tightly bound to the inner
mitochondrial membrane.

7. Fumarase: Hydration of Fumarate to malate: It is a highly

stereospecific enzyme. Cis-Maleate (the cis form of fumarate is not
recognized by this enzyme.

8. L-Malate dehydrogenase: Oxidation of malate to oxaloacetate: It is an

NAD+dependent enzyme. Reaction is pulled in forward direction by the
next reaction (citrate synthase reaction) as the oxaloacetate is depleted
at a very fast rate.

Products of the citric acid cycle

In a single turn of the cycle:
two carbons enter from acetyl CoA, and
two molecules of carbon dioxide are
released;
three molecules ofNADH and one
molecule ofFADH2 are generated; and
one molecule ofATP or GTP is produced.

Each glucose produces two acetylCoA molecules,

so we need to multiply these numbers by2if we
want the per-glucose yield.
Two carbonsfrom acetylCoAenter the citric acid
cycle in each turn, and two carbon dioxide
molecules are released. However, the carbon
dioxide molecules dont actually contain carbon
atoms from the acetylCoA, that just entered the
cycle. Instead, the carbons from acetylCoAare
initially incorporated into the intermediates of the
cycle and are released as carbon dioxide only
during later turns. After enough turns, all the
carbon atoms from the acetyl group of acetylCoA
will be released as carbon dioxide.

The total number of ATP

obtained after complete
oxidation of one glucose in
glycolysis, citric acid cycle, and
oxidative phosphorylation is
estimated to be between 30
and 38

THANK YOU!

READY?

QUIZ NO.2

1. Give another name for Citric Acid Cycle.

2. Before entering the Citric acid cycle, pyruvate is
converted to ____________.
a. Glucose
b. Water and carbon dioxide
c. Acetic acid
d. Acetyl COA
e. Oxaloacetate
3. TRUE OR FALSE. Citric Acid Cycle is a series of
enzyme-catalyzed chemical reactions that form a key
part of aerobic respiration in cells.
4. TRUE OR FALSE. The Citric Acid cycle occurs in the
mitochondrion.
5. Who showed that succinate is formed from fumarate,
malate or oxaloacetate? That Pyruvate can form citrate
enzymatically.

6-13.
COMPLETE
THE CYCLE

ACETYLCOA

7.

6.

8.
NAD
H

13.

9.
NAD
H

12.

FAD

10.
AT
P

11.

NAD
H

SUCCINYLCOA

14. A single turn of the Citric acid cycle will

yield
a. 1 ATP, 2 NADH, and 1 FADH2.
b. 1 ATP, 2 NADH, and 2 FADH2.
c. 1 ATP, 3 NADH, and 1 FADH2.
d. 2 ATP, 2 NADH, and 2 FADH2.
e. 2 ATP, 3 NADH, and 2 FADH2.
15. Give one enzyme present in the citric
acid cycle.

Answers

1. Give another name for Citric Acid Cycle.

ANS: KREBS CYCLE OR TRICARBOXYLIC CYCLE
2.Before entering the Citric acid cycle, pyruvate is converted to
____________.
a. Glucose
b. Water and carbon dioxide
c. Acetic acid
d. Acetyl COA
e. Oxaloacetate
3. TRUE OR FALSE. Citric Acid Cycle is a series of enzyme-catalyzed
chemical reactions that form a key part of aerobic respiration in cells.
4. TRUE OR FALSE. The Citric Acid cycle occurs in the mitochondrion.
5. Who showed that succinate is formed from fumarate, malate or
oxaloacetate? That Pyruvate can form citrate enzymatically.
ANS: HANS KREBS

ACETYLCOA

COMPLETE THE CY

7.

6.

CITRATE

8.

OXALOACETA
TE

13.

CIS ACONITATE

NAD
H

9.

MALATE

ISO CITRATE

NAD
H

12.

FAD

FUMARATE

11.

10.

KETOGLUTARATE

AT
P

SUCCINATE

NAD
H

C
SUCCINYLCOA

14. A single turn of the Citric acid Cycle will yield

a. 1 ATP, 2 NADH, and 1 FADH2.
b. 1 ATP, 2 NADH, and 2 FADH2.
c. 1 ATP, 3 NADH, and 1 FADH2.
d. 2 ATP, 2 NADH, and 2 FADH2.
e. 2 ATP, 3 NADH, and 2 FADH2.
15. Give one enzyme present in the citric acid
cycle.
ANS:
ACONITASE
ISOCITRATE DEHYDROGENASE
KETOGLUTARATE DEHYDROGENASE
COMPLEX
SUCCINYL-COA SYNTHETASE
SUCCINATE DEHYDROGENASE
FUMARASE