Know in one minute about Pyruvate oxidation

Pyruvate oxidation produces ATP by breaking the sugar molecules.  It is of two types namely aerobic oxidation and anaerobic oxidation. It occurs in the mitochondrial matrix. This reaction is catalyzed by PDH (pyruvate dehydrogenase) complex which is found in the mitochondrial matrix. PDH complex is a multienzyme complex, it is consist of three enzymes- Pyruvate dehydrogenase (E1), Dihydrolipoyl transacetylase (E2), and Dihydrolipoyl dehydrogenase (E3), with its cofactor NAD and FAD. Pyruvate oxidation connecting link between glycolysis and Kreb cycle. In this, the end product of glycolysis pyruvate converts into acetyl CoA.  NAD is converted into NADH and CO2 is produced.

Introduction

Pyruvate Oxidation

The oxidation or we can say the addition of oxygen to pyruvic acid is known as pyruvate oxidation. It is of two types namely aerobic oxidation and anaerobic oxidation. When the oxidation of pyruvic acid occurs in the presence of oxygen it’s called aerobic oxidation. And when it happens in the absence of oxygen it’s called anaerobic oxidation.

Some animal cells have both aerobic oxidation and anaerobic oxidation.

Pyruvate Oxidation types

1. Aerobic Oxidation  
2. Anaerobic Oxidation

1. Anaerobic Oxidation

Anaerobic oxidation occurs in the absence of Oxygen.

Example of Anaerobic oxidation

1. Lactic acid formation in animal cells.

This reaction is catalyzed by lactate dehydrogenase enzymes. This is called the fermentation process.

               Pyruvate + NADH    →    Lactate + NAD+

2. Alcoholic fermentation of pyruvic acid in Plants

Anaerobic oxidation of pyruvic acid occurs in yeast cells. This Reaction completes in two stages.

1. Decarboxylation of pyruvic acid

In the presence of decarboxylase enzymes, pyruvic acid converts into acetaldehyde and CO2 gas is released.

CH3.CO.COOH (Pyruvic acid)       →    CH3CHO(Acetaldehyde) + CO2(Carbon dioxide)

2. Formation of ethyl alcohol

In the presence of alcohol dehydrogenase enzyme acetaldehyde reacts with NADH2 and forms ethyl alcohol.

CH3CHO (Acetaldehyde) + NADH2    →      CH3CH2OH (Ethyl alcohol) + CO2 + NAD

2. Aerobic Oxidation

• Aerobic oxidation takes place in the presence of oxygen. In this process of oxidation, molecules lose one or more electrons. 
• This reaction is like a junction point between glycolysis and the Krebs cycle. 
• Glycolytic end product Pyruvate converts into Acetyl CoA by oxidative decarboxylation. 
• The carboxyl group of pyruvate is lost as CO2, while the remaining two carbons form the acetyl moiety of acetyl CoA.
• This is an irreversible reaction, catalyzed by pyruvate dehydrogenase complex (PDH), it is a multienzyme complex and found only in the mitochondria.

The three enzymes involved are assembled into a highly organized multienzymes assembly called the pyruvate dehydrogenase complex. High activity of PDH is found in cardiac muscle and kidney. The enzyme PDH requires five cofactors namely, TPP, lipoamide, FAD, coenzyme A, NAD+

PDH catalyzes the reaction

Pyruvate + NAD+ + CoA    →     Acetyl CoA + CO2

Pyruvate oxidation steps

It is catalyzed by PDH complex. The sequence of reactions brought about by different enzymes of the PDH complex in association with the coenzyme.

Firstly the carboxyl group is removed from pyruvate as a molecule of CO2  and another two carbons become the acetyl group of acetyl CoA this process is also called oxidative decarboxylation. In this reaction, NADH formed.

The reaction of PDH complex

PDH complex contains three enzymes, Pyruvate dehydrogenase complex (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3). Each enzyme is present in multiple copies.

Pyruvate is decarboxylated to give hydroxyethyl TPP, catalyzed by PDH. Dihydrolipoyl transacetylase forms acetyl lipoamide from hydroxyethyl- TPP.

Then acetyl groups transfer to coenzyme A and produce acetyl CoA. The cycle is complete when reduced lipoamide is converted to oxidized lipoamide by dihydrolipoyl dehydrogenase, transferring the reducing equivalents to FAD. FADH2, in turn, transfers the reducing equivalents to NAD+ to give NADH + H+ which can pass through the respiratory chain. The intermediate of PDH-catalyzed reactions is not free but bound with an enzyme complex.

Significance

• Pyruvate oxidation is important to produce energy in the ATP form from the breakdown of sugar. 
• Sugar breakdown in pyruvate by glycolysis then pyruvate converts into acetyl CoA by pyruvate oxidation. This acetyl CoA works as fuel for the Krebs cycle. 
• Pyruvate oxidation and Krebs cycle both are important for aerobic respiration. TCA cycle hub in metabolism.
• This is important to the brain, which obtains all its energy from the aerobic oxidation of glucose in a pathway.

Interesting facts about Pyruvate oxidation

• In aerobic respiration, the end product of glycolysis is transferred to the mitochondria where pyruvate oxidation takes place, and acetyl CoA is taken up by a TCA or Krebs cycle.
• Pyruvate oxidation connecting link between glycolysis and Krebs cycle. 
• Glycolysis end product Glucose is oxidized to acetyl CoA and carbon dioxide by pyruvate dehydrogenase complex. 
• This enzyme is located in mitochondria.  
• Pyruvic oxidation product Acetyl CoA enters in TCA cycle and produces CO2 H2O. Pyruvate oxidation produces acetyl CoA to the Krebs cycle to produce energy. 
• Pyruvate dehydrogenase has an important contribution to completing this reaction.
• The PDH complex is a multienzyme complex, it is consist of three enzymes

1. Pyruvate dehydrogenase (E1), is bound with TPP cofactor.
2. Dihydrolipoyl transacetylase (E2), with its covalently bound lipoyl group.
3. Dihydrolipoyl dehydrogenase (E3), with its cofactor NAD and FAD.

• E1 catalyzes the decarboxylation of pyruvate and produces hydroxyethyl- TPP, then the oxidation of the hydroxyethyl group to an acetyl group.
• E2 catalyzes the transfer of the acetyl group to coenzyme A, and produces acetyl CoA.
• E3 catalyzes the oxidation of lipoamide, and passes electrons first to FAD, and then to NAD+

Clinical significance

Thiamine deficient are unable to oxidize pyruvate normally, this is very important for the brain because the brain produces all its energy by aerobic oxidation.

Beriberi disease is the result of thiamine deficiency, and loss of neural function is one of its characteristics.

Q&A

1. Where does Pyruvate oxidation occur?

Pyruvate oxidation occurs in the mitochondrial matrix. This reaction is catalyzed by the PDH complex which is found in only the mitochondrial matrix.

2. Does pyruvic oxidation requires oxygen?

Yes, aerobic oxidation requires Oxygen, which it converts to acetyl CoA. But in anaerobic oxidation oxygen is not required for the oxidation of pyruvate.

3. What is Pyruvate oxidation?

The end product of glycolysis pyruvate converts into acetyl CoA, this reaction is catalyzed by pyruvate dehydrogenase complex. NAD is converted into NADH and CO2 is produced.

4. Where does Pyruvate oxidation take place?

It occurred in the mitochondrial matrix.

5. What does Pyruvate oxidation produce?

In pyruvate oxidation pyruvate converts into acetyl CoA, NADH2, and carbon dioxide produced as a by-product.

References

1. 4th edition biochemistry By Donald Voet & Judith G. Voet.

2. Lehninger, 4th edition, Principal of biochemistry By David L. Nelson & Michael Page No. 792.

3. Biochemistry, 4th edition, U. Satyanarayana, U. Chakrapani (Page No. 479 to 481).

Written By: Richa Pachori