Do you remember the final product of glycolysis? Yes, it is pyruvate. The pyruvate obtained after glycolysis act as the connecting link between different processes of metabolism.
The fate of pyruvate is the catabolism (breakdown) of pyruvate depending on the oxygen levels of the cell. Let’s say, the cells that produce pyruvate are aerobic (eukaryotic cells with mitochondria) then pyruvate follows its aerobic future of converting into acetyl-CoA. Similarly, in the condition of hypoxia in cells (lactic acid bacteria, skeletal muscles, plants, etc.), the pyruvate needs to follow the anaerobic fate, either formation of lactate or ethanol.
Hypoxia: deficiency of oxygen in cell
Table of Contents
The Three Fates of Pyruvate
The most common future of pyruvate are as follows:
- Lactate formation
- Ethanol formation
- Acetyl CoA formation
Lactate Formation or Lactic Acid Fermentation (Anaerobic Fate of Pyruvate)
This process occurs in animal tissues that cannot supply enough oxygen or lack mitochondria to carry out the aerobic oxidation process of pyruvate and NADH. It can also occur in a wide range of microorganisms.
The enzyme catalyzing the reaction is lactate dehydrogenase (LD).
NAD is an essential electron acceptor in glycolysis. It is regenerated while converting pyruvate to lactate. Even though there is the production of NAD, there is no net change in NAD or NADH. This is because the sixth step of converting glyceraldehyde-3-phosphate to1,3-biphosphoglycerate of glycolysis utilizes it again.
The lactate that is produced during heavy exercise in skeletal muscles is recycled as glucose during the rest. A net of 2 ATP can be obtained from glycolysis to lactic acid fermentation.
Ethanol Formation or Alcoholic Fermentation (Anaerobic Fate of Pyruvate)
Some microorganisms and yeast follow another fate of pyruvate. It is ethanol formation or alcoholic pathway instead of lactic acid fermentation to produce ATP.
The conversion of pyruvate to ethanol has 2 different steps:
- Conversion of pyruvate to acetaldehyde: Firstly, in the presence of the enzyme pyruvate decarboxylase (PD), the pyruvate is decarboxylated into acetaldehyde. A molecule of carbon dioxide is released in this step. The enzyme needs magnesium ions and coenzyme thiamine pyrophosphate (TPP) as cofactors. It is an irreversible reaction.
- Conversion of acetaldehyde to ethanol: Finally, acetaldehyde is reduced to ethanol in this step with the help of the enzyme alcohol dehydrogenase and NADH.
The end products of this step are ethanol and carbon dioxide. Like lactate fermentation, there is no net change in NAD or NADH in this fermentation. The net ATP gain is two from glycolysis to alcoholic fermentation.
Decarboxylation: removal of carboxyl group
Aerobic Fate of Pyruvate
The aerobic fate of pyruvate is the oxidative decarboxylation of pyruvate to acetyl coenzyme A. Pyruvate dehydrogenase complex (PDC) catalyzes the reaction. PDC is a group of 3 enzymes E1; pyruvate dehydrogenase, E2;dihydrolipoyl transacetylase, and E3; dihydrolipoyl dehydrogenase. It also requires five coenzymes or factors to operate. They are;
- TPP( Thymine Pyrophosphate): TPP has the role of a transient carrier of the 2-carbon molecule of 3-carbon pyruvate in hydroxyethyl or active acetaldehyde.
- FAD (Flavin Adenine Dinucleotide): FAD is an electron carrier.
- Coenzyme A or CoA or CoASH: Coenzyme A has an active thiol group that has the role of transferring the acyl group in the form of thioesters.
- NAD (Nicotinamide Adenine Dinucleotide): Like FAD, NAD is also an electron carrier in the reaction.
- Lipoamide: Lipoamide has two thiol groups which undergo reversible oxidation. It can function as both an electron hydrogen carrier and an acyl carrier in the aerobic fate of pyruvate.
Firstly, the function of E1 is removing a carbon group of pyruvate producing hydroxyethyl-TPP. The oxidation of pyruvate to an acetyl group is another function of the E1 enzyme. The oxidation generates electrons, which reduces the disulfide of lipoamide bound to the E1 enzyme. The acetyl group to the one free OSH group of the reduced. This step produces a molecule of carbon dioxide.
In the same way, E2 help in catalyzing the transfer of the acetyl group from lipoamide to coenzyme A, resulting in formation of acetyl CoA.
Finally, the E3 enzyme helps in regenerating the disulfide form of lipoamide. It also helps in electron transfer first to FAD and NAD.
The next step after the aerobic breakdown of pyruvate to acetyl Coenzyme A is entering into the Krebs cycle.
Oxidation is the process of releasing hydrogen ions whereas reduction is the process of gaining hydrogen ions.
Reference
- Lehninger, A., Nelson, D., Cox, M., & Osgood, M. (2005). Lehninger principles of biochemistry (4th ed., pp. 538-606). W.H. Freeman.
- Prochownik EV, Wang H. The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells. Cells. 2021 Mar 30;10(4):762. DOI: 10.3390/cells10040762. PMID: 33808495; PMCID: PMC8066905.
