The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle, is a series of chemical reactions that generates energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. It is an amphibolic pathway that occurs in the mitochondrial matrix. The cycle produces carbon dioxide and electron carriers NADH and FADH2 that drive oxidative phosphorylation to produce ATP. Tracing the fate of acetyl-CoA carbon atoms through the cycle revealed that the two carbons are not immediately released as CO2 but are instead incorporated into oxaloacetate and later released, demonstrating the reactivity and roles of cycle intermediates.

1. KREBS CYCLE
&
FATE OF ACETYL COA CARBON IN
THE TCA CYCLE
Pranjal Gupta, Bsc(H) Zoology, Ramjas College,
University of Delhi

2. SO WHAT IS KREBS CYCLE ?
 Krebs cycle or Citric acid
cycle or Tricarboxylic
acid(TCA) cycle is a series
of chemical reactions to
generate energy and
release CO2 by utilization
of acetyl CoA molecule.
 Hanz Adolf Krebs received
Nobel prize in physiology
and medicine in 1953.
 http://www.nobelprize.org/
nobel_prizes/medicine/laur
eates/1953/krebs-bio.html
 It is an amphibolic
pathway
Image source: Google

3. WHAT IS THE
SIGNIFICANCE OF
SUCH A COMPLEX
CYCLE ?

4.  Acetyl CoA produced as the end result of oxidative
decarboxylation of Pyruvate is also produced by a
no. of non carbohydrate sources including fats and
proteins. It links every metabolism.
 It is an energy providing pathway, no matter how
much complex !
 It has 8 intermediates, almost all of which are
required for some or the other process(discussed
later).
 Intermediates of the Krebs cycle are replenished by
various anaplerotic reactions.
 It is a biochemical evidence of evolution.

5. ACETYL COA IS PRODUCED FROM VARIOUS
SOURCES

7. Interconnection
of metabolic
Pathways
Processes mentioned include:
1. Glycogenesis-Breakdown of
glycogen to produce glucose in
liver and muscles.
2. Glycogenesis-
Storage of blood glucose as
glycogen in liver(mostly) for
later use.
3. Gluconeogenesis-
Production of glucose from non-
carbohydrate precursors.
4. Glycolysis-
first step to cellular respiration,
i.e. breakdown of glucose to
pyruvate.
5. Fermentation
A step to anaerobic respiration
that occur in yeast to produce
ethanol and carbon dioxide.
6. Beta-oxidation-common &
important fatty acid breakdown
7. Urea cycle
In ureotelic organism to convert
ammonia to urea

8. KREBS CYCLE IS AN ENERGY PROVIDING PATHWAY Electron acceptor molecules
generated(for single acetyl coa):
1. 1 NADH/H+ during isocitrate to α
Ketoglutarate conversion under the
enzyme isocitrate dehydrogenase.
2. 1 NADH/H+ during α Ketoglutarate to
succinyl coa conversion under the
enzyme α Ketoglutarate dehydrogenase.
3. 1 ATP after Transphosphorylation with
GTP produced in succinyl coa to
succinate conversion
4. 1 FADH2 during succinate to fumarate
conversion under the enzyme succinate
dehydrogenase-which is the only enzyme
of Krebs cycle located on the inner
membrane of mitochondria.
5. 1 NADH/H+ during malate to
oxaloacetate conversion under enzyme
malate dehydrogenase.
6. Overall composition is 6 NADH/ H+,
2FADH2 and 2ATP for two Acetyl coa(
produced from 2 pyruvates from
glycolysis)
7. Also conversion of a pyruvate to acetyl
coa utilises a NAD+ molecule under
pyruvate dehydrogenase complex.
8. This leads to 2 pyuvate to Krebs cycle:
8 NADH/H+, 2FADH2, 2ATP

12. According to other convention 36-38 ATP molecules are generated.

13. INTERMEDIATES OF CYCLE ARE USEFUL , AND ALSO
THEY’RE REPLENISHED.
http://www.bioinfo.org.cn/book/biochemistry/chapt15/464.jpg

14. http://slideplayer.com/slide/3419004/

15. WHAT DO YOU MEAN BY FATE ?

16. Krebs cycle is
like different phases
Of our life, where
each phase(aspirations)
signify the different
intermediates of the cycle
as they change from one
form to another, till there
comes a point where we
are dedicated to one
work( except if we are
more into exploration). At
this point a child is born
which again repeats the
cycle with different
aspirations at different
stages.
FROM ANOTHER PERSPECTIVE

17. SO WHAT’RE WE GOING TO DO OR LEARN
HERE ?
 When we talk about fate of CARBON in TCA cycle,
we talk entirely at atomic level
 But it is difficult to understand the importance of
atom if we do not understand the importance of the
molecule they’re in.
 Before jumping directly to how carbon atom of the
acetyl coA is utilized it is essential to know how the
molecules of the cycle even interact !
 Difference between methyl and carbonyl carbon is
must, because their fates differ.
 Symmetry of molecules interfere with site of
reaction.

18. INCORPORATION OF ACETYL COA TO ALPHA-
KETOGLUTARATE

19. CITRATE BEING A SYMMETRICAL MOLECULE
INTERACT ASYMMETRICALLY
Source: Lehninger Principles of Biochemistry

20. Lehninger
principles
Of
biochemistry

21. NOW WE KNOW HOW THE REACTANTS INTERACT, IT
IS TIME TO GO TO THE ATOMIC LEVEL.

23. CONCLUSION:
 Krebs cycle forms the essential part of the
metabolism of almost every eukaryotic organism.
 It involves one very important step of cellular
respiration that is removal of two molecules of
carbon dioxide with entry of acetyl coA
 It was perceived that in the single turn the CO2
released was of the carbons of acetyl coA itself.
 Experimental studies of fate of carbon atom reveals
that acetyl coA carbons are preserved in the first
turn and are incorporated in a newly formed
oxaloacetate and later released.
 Such studies also helped to understand the
reactivity of the intermediates involved.

24. REFERENCES
 Nelson, D. L., Cox, M. M. and Lehninger, A.L. (2009).
Principles of Biochemistry. IV Edition. W.H Freeman and Co.,
Chapter 16 The Citric Acid Cycle
 www.Boundless.com/ Textbooks/ Boundless Biology/ Cellular
respiration/Oxidation of pyruvate and the citric acid cycle/
Acetyl CoA to CO2
 Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition.
New York: W H Freeman; 2002. Section 17.1, The Citric Acid
Cycle Oxidizes Two-Carbon Units. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK22427/
 Chapter 19 The Tricarboxylic Acid Cycle Biochemistry by
Reginald Garrett and Charles Grisham
 Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition.
New York: W H Freeman; 2002. Section 18.5, Many Shuttles
Allow Movement Across the Mitochondrial
Membranes. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK22470/