Krebs Cycle – Cellular Respiration (Part – IV)

By | October 27, 2021
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  • The fate of pyruvic acid formed at the end of Glycolysis depends on the need of the cell and also on availability of oxygen.
  • Organisms which grow in absence of oxygen – In anaerobic organisms, fermentation takes place after glycolysis.
  • In presence of oxygen, aerobic respiration takes place where pyruvic acid from glycolysis enter Krebs’s Cycle, Electron transport system and oxidative phosphorylation.
  • In aerobic respiration ( a type of cellular respiration), complete oxidation of glucose is observed and this allows to extract the energy which will be used to synthesize additional number of ATPs, which will be used for various cellular needs.
  • These steps takes place in mitochondria of the cell.
  • Aerobic respiration can be defined as complete oxidation of glucose or organic substances in presence of oxygen to extract lot of energy along with release of CO2 and water.
  • Aerobic respiration is common in majority of evolved or higher organisms.

Key events of aerobic respiration

The important events of an aerobic respiration can be divided into two parts :

1– Pyruvic acid from glycolysis is subjected to complete oxidation by step wise removal all hydrogen atoms to leave just three molecules of CO2. This event takes place in matrix of Mitochondria.

2– The electrons removed as part of hydrogen atoms are passed through series of electron carriers and finally to molecular oxygen with simultaneous generation of ATP. This event occurs in the inner membrane of Mitochondria.

The final product of glycolysis is pyruvic acid – to be more precise – one molecule of glucose gives rise to 2 molecules of pyruvic acid at end of glycolysis.

Breaking down of Pyruvic acid:

Each pyruvate molecule produced by glycolysis in cytoplasm is transported across the inner mitochondrial membrane and into the matrix of mitochondria, where it is decarboxylated to form a two-carbon acetyl group.

This acetyl group is transferred to coenzyme A (a complex organic compound derived from the vitamin pantothenic acid) to produce acetyl CoA.

In this process CO2 is released (decarboxylation) and important to remember one out of six carbons from original glucose molecule is removed in this step. NAD+ picks up electrons to form NADH, which will be used later.

The conversion of pyruvic acid to acetyl coenzyme A is catalyzed by the giant multienzyme complex pyruvate dehydrogenase.

There are many ways acetyl CoA can be used by the cell, however its main function is to deliver the acetyl group derived from pyruvic acid to the next stage of the pathway in glucose catabolism.

The reaction of converting pyruvic acid into acetyl co A acts as connecting link between glycolysis and Krebs cycle.

Pyruvic acid to Acetyl CO A

Krebs Cycle

The acetyl co A formed is integrated into a cyclic pathway called as Krebs cycle, named after British biochemist Hans Krebs, who discovered the pathway in minced Pigeon breast muscle tissue.

When Hans Kreb had deciphered the cycle, he submitted the esults to Nature Journal for publication. However it was rejected as editor had enough letters to publish for eight to nine weeks (June 1937). The article was later published in Enzymologia.

Hans Krebs proudly displayed the rejection letter throughout his career as encouragement for young scientists.

Acetyl Co A is the entry point into Krebs cycle, where the substrate is oxidized and its energy conserved.

The Krebs cycle happens to be final common pathway for the oxidation of many fuel molecules such as amino acids, fatty acids, and carbohydrates. They all enter Krebs cycle as acetyl coenzyme A.

Krebs cycle is also termed as “the central metabolic hub of the cell“.

There are other names to Krebs cycle – such as Tricarboxylic acid (TCA) or Citric acid cycle. They are called such that as the first compound formed in Krebs cycle is Citric acid which has COOH groups or tricarboxylic in nature.

Step -1 Acetyl co A enters the cyclic pathway and the first step involves condensation of acetyl group with oxaloacetic acid (OAA) and water to form Citric acid. The enzyme required for the reaction is citrate synthase and it release co A

Step – 2 Citric acid is isomerised in presence of Acotinase to form Isocitric acid (isocitrate).

Step -3 Isocitric acid is oxidized to form 5 carbon alpha keto glutaric acid. Here CO2 is released (decarboxylation) along with two electrons, which reduce NAD+ to NADH. The enzyme employed here is isocitrate dehydrogenase.

Step -4 Alpha ketoglutaric acid is again oxidized to form succinic- CoA in presence of CoA. In this reaction also ( as in step-3) loss of CO2 (carboxylation) and release electrons that reduce NADto NADH are observed. The enzyme which catalyzes this reaction is alpha ketoglutarate dehydrogenase.

Step – 5 In this step five, a carboxyl group is substituted for coenzyme A, and a high-energy bond is formed. This energy is used in substrate-level phosphorylation (during the conversion of the succinyl group to succinate) to form either guanine triphosphate (GTP) or ATP. The enzyme used here is Succinyl-CoA synthase to covert succinic- CoA to succinic acid.

Step – 6 Succinic acid is then converted to Fumaric acid in presence of succinate dehydrogenase only enzyme present in inside the inner membrane of the mitochondrion, other enzymes of Krebs cycle are dissolved in matrix). Here, two hydrogen atoms from succinic acid are transferred to FAD, reducing it to FADH2.

Step – 7 Next, fumaric acid is converted to malic acid by hydrolysis in presence of water. This reaction is controlled by Fumerase.

Step – 8 Last step of Krebs cycle results in regeneration of oxaloacetic acid from oxidation of malic acid. Again another molecule of NADH is produced in the process. Malate dehydrogenase catalyzes this reaction required for regeneration of oxaloacetic acid (OAA)

The regenerated OAA will allow the cycle to continue by condensing with new molecule of acetyl CoA.

5 pairs of high energy electrons (from hydrogen atoms of substrates) are transferred to NAD+ or FAD and then passed down the electron-transport chain for use in ATP production.

To sum up, during the Krebs cycle- the citric acid molecule is decreased in chain length, one carbon at a time, to form the four-carbon OAA molecule, which can begin or condense with another acetyl CoA to restart the cycle.

Important energy components of cellular respiration:

ATP (Adenosine triphosphate): The energy currency of the cell. ATP is a high-energy molecule that stores and transports energy within cells.

NADH: High energy electron carrier used to transport electrons generated in Glycolysis and Krebs Cycle to the Electron Transport Chain.

FADH2: High energy electron carrier used to transport electrons generated in Glycolysis and Krebs Cycle to the Electron Transport Chain.

Krebs Cycle


So far we have seen, glucose molecule is broken down to form total 8 molecules of NADH + H+, 2 molecules of FADH and just 2 molecules of ATP. ( remember for each glucose molecule – 2 molecules of pyruvic acid will enter into Krebs cycle – so if for each molecule of pyruvic acid – 4 NADH + H+ , 1 FADH2 and 1 ATP are formed then it comes to a total of 8 molecules of NADH + H+, 2 molecules of FADH and 2 molecules of ATP )

Many might be wondering, where does oxygen comes into this picture of aerobic respiration? So far in Glycolysis and Krebs cycle, oxygen was also not utilized at any place.

Another thing which might be confusing is such a low output of ATPs from Krebs cycle – only 2 ATPS. Because in aerobic respiration as compared to anaerobic respiration, oxidation of glucose was supposed to give us a large number of ATPs.

To get answers to the above two important questions , we will look into the fate of NADH + H+ and FADH2 formed during glycolysis and Krebs cycle in the next post about electron transport system and oxidative phosphorylation and . In electron transport system and oxidative phosphorylation we will also realize the importance of oxygen during aerobic respiration.


The citric acid cycle and the Szent-Györgyi cycle in pigeon breast muscle – Hans Kreb

Biochem J. 1940 May; 34(5): 775–779.doi: 10.1042/bj0340775

Introduction Cellular Respiration : Part I

Glycolysis : Part II Cellular respiration.

Fermentation : Part III Cellular Respiration

Krebs Cycle : Part IV Cellular Respiration.

Electron Transport Chain and Oxidative Phosphorylation : Part V Cellular Respiration

Image Credit: Openstax Biology