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

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/laureates/1953/krebs-bio.html

It is an amphibolic pathway

Image source: Google

WHAT IS THE SIGNIFICANCE

OF SUCH A COMPLEX CYCLE

?

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.

ACETYL COA IS PRODUCED FROM VARIOUS SOURCES

Interconnectionof metabolic

PathwaysProcesses 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 breakdown7. Urea cycle

In ureotelic organism to convert ammonia to urea

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

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

INTERMEDIATES OF CYCLE ARE USEFUL , AND ALSO THEY’RE REPLENISHED.

http://www.bioinfo.org.cn/book/biochemistry/chapt15/464.jpg

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

WHAT DO YOU MEAN BY FATE ?

Krebs cycle is like different phasesOf our life, whereeach 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

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.

INCORPORATION OF ACETYL COA TO ALPHA-KETOGLUTARATE

CITRATE BEING A SYMMETRICAL MOLECULE INTERACT

ASYMMETRICALLY

Source: Lehninger Principles of Biochemistry

Lehninger principles Of biochemistry

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

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.

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/