Acetyl CoA

Introduction

  • Acetyl CoA is a vital compound in cellular respiration.
  • It is produced from carbohydrates, protein or amino acids, and lipids.
  • It is a key player in the metabolism of carbohydrates, proteins, amino acids, and lipids.
  • Where it helps in the breakdown of food to create energy.
  • It is known as metabolite as it is both made and used during metabolism.
  • Also serves as a fuel and a starting point in the Krebs cycle, a common pathway for carbohydrates, proteins, and lipids, which produce energy.
  • This enzyme also enters the TCA cycle and completely degrades into CO2, H2O, and ATP molecules.
  • Thus Acetyl CoA is an essential energy-producing compound in all living organisms.

Acetyl CoA function

  • Intermediate in Kerb’s cycle

Acetyl CoA serves as an intermediate for Kerb’s cycle also known as the citric acid cycle in there his goal of producing adenosine triphosphate (ATP)

ATP is the high energy molecule in the body because it contains enough energy to derive biochemical reactions forward.

  • In cellular respiration

Also is an intermediate of cellular respiration, it converts food to energy in the aerobic condition.

  • Fatty acid metabolism

Exist as a metabolite from the breakdown of carbohydrates, proteins, and lipids. The breakdown of lipids is referred to as fatty acid metabolism.

  • Steroids synthesis

Participates in the mevalonate pathway.

  • Used in cholesterol

This enzyme is also important for the production of cholesterol, steroids, hormones, and bile acids.

It also provides the acetyl group necessary for various metabolic reactions.

What do alcohol fermentation, acetyl CoA formation and the Krebs cycle have in common?

Alcohol fermentation, acetyl CoA formation, and Kerb’s cycle all produce carbon dioxide as a by-product.

1. Alcohol fermentation

In yeast cells Ethyl alcohol,  NAD, and CO2 are produced by the oxidation of pyruvic acid this reaction is called alcohol fermentation.

This process completes in Anaerobic conditions. Alcohol fermentation is completed in the following stages

(a) Decarboxylation of pyruvic acid

Decarboxylation of pyruvic acid occurs in the presence of the Pyruvic decarboxylase enzyme and produces acetaldehyde.

CH3.CO.COOH (Pyruvic acid)   →    CH3.CHO (acetaldehyde)  + CO2

(b) Formation of Ethyl alcohol

In the presence of an alcohol dehydrogenase enzyme, acetaldehyde reacts with NADH2 and produces ethyl alcohol, NAD, and CO2.

CH3CHO (acetaldehyde) + NADH2    →      CH3CH2OH + CO2 + NAD

2. Acetyl CoA formation

Acetyl CoA is produced by oxidative decarboxylation of Pyruvic acid. In this reaction, one molecule of carbon dioxide is released.

Pyruvic acid + CoA + NAD      →      Acetyl CoA + NADH2

This reaction takes place in the mitochondrial matrix. Pyruvic acid which is produced in cytosol reacts with CoA which is a sulfur-containing compound and produces NADH2 and CO2 and the end produces Acetyl CoA.

This reaction complete with the help of cofactors and many enzymes which are called Pyruvic Dehydrogenase complex, these enzymes are namely Pyruvic acid decarboxylase, dihydrolipoyl transacetylase, dihydrolipoyl dehydrogenase.

3. Krebs cycle

In this process, CO2 and H2O are produced as end products. It is a cyclic pathway where inorganic compounds such as CO2 and H2O are formed by the complete degradation of acetyl CoA.

This reaction takes place in the mitochondrial matrix, it is the third stage of respiration. Acetyl CoA works as a fuel in Kerb’s cycle. 

Acetyl CoA + 2H2O + 3NAD + FAD + GDP + iP       →      2Co-A + 2CO2 + 3 NADH 2 + FADH2 + GTP

So we can say CO2 is a common by-product in Kerb’s cycle, Alcohol fermentation, and acetyl CoA.

During cellular respiration, acetyl CoA accumulates in which location?

During cellular respiration, acetyl CoA accumulates inside mitochondria. It is stored and according to the body’s needs provides energy via the TCA cycle.

Cellular respiration

  • To produce energy, cells perform degradative reactions that are called cellular respiration, in this simple sugars, fatty acids, and amino acids work as fuels. Produced energy is stored in ATP form.
  • Glycolysis is the first step of cellular respiration where six-carbon glucose molecules degrade into Pyruvic acid.
  • Under aerobic conditions, Glycolysis end product Pyruvic acid enters mitochondria and produces acetyl CoA by oxidative decarboxylation. It is a very highly complex reaction that is catalyzed by pyruvate dehydrogenase complex.
  • Acetyl CoA is the common intermediate formed by the breakdown of most metabolic fuels.
  • It is produced by lipid, carbohydrate, and Protein metabolism.

Note: Acetyl CoA is a connecting link between glycolysis and the TCA cycle and it is a high-energy compound. The TCA cycle is the third stage of cellular respiration. Acetyl CoA which occurs in the mitochondrial matrix is used by the TCA cycle for producing energy.

Where does Acetyl CoA formation occur?

Acetyl CoA formation occurs in the mitochondrial matrix. It is a metabolite derived from glucose, fats, and amino acids. It is produced by

  •  Glucose metabolism
  • Fatty acid oxidation
  • Amino acid deamination

Each can act as a source of acetyl CoA. 

Formation of Acetyl CoA by pyruvate Oxidation

Pyruvate Oxidation occurs in mitochondria, there acetyl CoA is produced by the Oxidation of pyruvate then this enters into TCA cycle which is a common oxidative pathway for all food substances.  

The product of glycolysis that is pyruvate is converted to acetyl CoA which is starting material of Kerb’s cycle this process is catalyzed by pyruvate dehydrogenase complex (PDH)

Pyruvate enters into mitochondria when a bond is broken, releasing carbon dioxide. The two carbon molecules that remain are called acetyl.

Oxidation of fatty acids

Acetyl CoA is also produced by the oxidation of fatty acids. This process also takes place in the mitochondrial matrix where fatty acids oxidize in acetyl CoA and acyl CoA. All enzymes which are responsible for the oxidation of fatty acids are present in the Mitochondrial matrix.

The acetyl CoA generated from beta-oxidation can be used in which of the following pathways?

It enters in Kerb’s cycle where it works as a fuel for produced energy. Its main function is to deliver the acetyl group to the Kerb’s cycle to be oxidized for energy production.

Beta oxidation is one of the sources of acetyl CoA, it is a very important intermediate compound in Kerb’s cycle.

What is beta-oxidation

Acetyl CoA is formed by the Oxidation of fatty acids. Oxidation of fatty acid occurs in beta-carbon atoms called beta-oxidation.

It is formed in the mitochondrial matrix, and all related enzymes that participate in the oxidation of fatty acid are present in the mitochondrial matrix which is called “fatty acid oxidase”.

These enzymes catalyze the oxidation of acyl CoA and produce acetyl CoA. 

Stages of beta-oxidation

  • Firstly acyl CoA enters mitochondria through the carnitine transporter system.
  • Then two hydrogen atoms are released from Alpha and beta carbon atoms and produce Alpha, a beta-unsaturated acyl coenzyme.
  • This reaction is catalyzed by the acyl CoA dehydrogenase enzyme in their flavoprotein which works as a coenzyme and FAD occurs as a prosthetic group.

1. Hydration of Alfa beta-unsaturated acyl CoA

Beta hydroxyacyl CoA produced by the addition of water in Alfa beta-unsaturated acyl CoA, enoyl CoA hydratase enzyme catalyzed this reaction.

2. Dehydrogenation of beta hydroxyacyl CoA

Dehydrogenation of beta hydroxyacyl CoA occurs on the beta carbon in the resulting beta ketoacyl CoA is produced. Beta hydroxyacyl CoA dehydrogenase catalyzed this reaction and NAD worked as a coenzyme.

Beta ketoacyl CoA is braked into two parts, acetyl CoA and acyl CoA. Acyl CoA again enters into the oxidative pathway and acetyl CoA enters into the TCA cycle. 

This enzyme serves as an intermediate of aerobic cellular respiration, the conversion of food to energy in the presence of oxygen. The Kerb’s cycle is just one pathway that is part of cellular respiration.

Krebs cycle occurs in the mitochondrial matrix. In the Kerb’s cycle 2 molecules of Acetyl CoA oxidized and formed 6 NADH2, 2 FADH2, and  2 ATP.

References

Written By: Richa Pachori

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