Fate Of Pyruvate

Fate of Pyruvate

Pyruvate is the last product that Glycolysis can give. So the overall reaction of glycolysis can be represented as:

Glucose + 2 NAD⁺ + ADP + 2 Pi → 2 pyruvate + 2 (NADH + H⁺) + 2 ATP + 2 H₂O

This sequential reaction is almost similar in all kinds of organism and cells. But the path pyruvate follows after its generation from glycolysis may vary organism to organism depending on their (organisms') nature of metabolism and condition they are facing. The Fate of pyruvate in the generation of energy can be either aerobic or aerobic path. So the fate of pyruvate depends on two factors, whether there is the presence of oxygen or not. The pyruvate may be converted to alcohol (ethanol), lactate (lactic acid), acetyl coA or oxaloacetate. Thus pyruvate is regarded as the most versatile intermediate molecule in metabolism.

Under anaerobic conditions pyruvate follows the fermentative pathway to yield either lactic acid or lactate in muscles and lactic acid bacteria, or ethanol and CO₂ in yeast cells. Similarly, under aerobic condition, pyruvate is converted into acetates that enter TCA cycle to yield ATPs.

Fate of Pyruvate in Anaerobic pathway:

The anaerobic pathway is conducted in the absence of oxygen whose end products can be lactic acid, ethanol or any such products along with CO_2. This pathway is termed as fermentative pathway because there is the partial breakdown of the substrate pyruvate. This pathway is comparatively less significant for the yield of energy. This process is commercially very important, though. Ethanol and lactic acid both are very important industrial products that have lots of economic values. So key product, pyruvate is regarded more important intermediate source of these all. Interestingly, there is no change in carbon is to hydrogen ratio in all fermentations with compared to the initial substrate, glucose (C : H= 6/12 = 1 /2).

• Ethanol Formation:

In some yeast cells and some other fermentative organisms fermentation of glucose to alcohol (ethanol) takes place rather than lactic acid. Pyruvate obtained after glycolysis of glucose is converted into alcohol undergoing a two-step reactions.

At the first pyruvate molecule undergoes decarboxylation reaction thus giving acetaldehyde as the intermediate product. This first step reaction is catalyzed by the enzyme, pyruvate decarboxylase and CO₂ is lost in this step.

Now in the second step of the reaction, the intermediate product, acetaldehyde is reduced to ethanol. This reaction is catalyzed by the enzyme, alcohol dehydrogenase. Here the reducing agent is NADH+H⁺ that in the course of the reaction is oxidized to NAD. The reaction involved can be represented as:

So the general reaction of fermentation can be given as follows:

Glucose→ → → → → → → Pyruvate + NADH + H⁺→→→→→→→ ethanol + CO₂

Alcohol dehydrogenase complex

• Lactic Acid (Lactate) Formation:

At some unfavorable conditions during which tissues of higher organisms are starved from the enough amount of oxygen supply, aerobic metabolism is impossible, then the metabolic pathway deviates towards the anaerobic conditions, thus producing an ultimate product, lactic acid or simply lactate. In lactic acid bacteria, this is the major pathway of metabolism.

This is the single step reaction and unlike in alcohol fermentation, here is no loss of CO₂. Here decarboxylase does not act and only the acting enzyme is dehydrogenase enzyme. NADH + H⁺ reduces the pyruvate molecule with the catalytic action of lactate dehydrogenase enzyme and the obtained product is lactate or lactic acid. The reaction seems to be like:

Lactic acid fermenting organisms mostly microorganisms are classified as homo fermentative and hetero fermentative lactic acid microorganisms. This depends on whether the organism produces only lactic acid or some other products as well?

Homo fermentative lactic acid microorganisms are those lactic acid producing organisms that produce only lactate as their metabolic product by the fermentation of glucose. Whereas hetero fermentative lactic acid microorganisms are those organisms that produce ethanol and CO₂ in addition to lactic acid by the fermentation of glucose. Some examples of lactic acid fermenting microorganisms are: Lactobacillus sps. , Leuconostoc, Streptococcus, Pediococcus etc. These all are bacterial species.

Fate of Pyruvate in Aerobic Pathway:

Aerobic pathway is conducted in the presence of oxygen whose end products can be any products like oxaloacetate or Acetyl co-enzyme A, which can take part in TCA cycle and can yield more amount of energy with compared to anaerobic one. This pathway is termed as oxidative pathway because there is the involvement of O₂ and a complete breakdown of the glucose. This pathway is comparatively more significant for the yield of energy. This process is biologically very important pathway. Acetyl CoA and oxaloacetate both are very important products that act as the fuel of TCA cycle. So key product, pyruvate is regarded more important intermediate source of these all.

• Acetyl coenzyme A formation:

It has been already discussed that in the anaerobic pathway, there is a critically low amount of energy yield. So in the case of higher organisms and most of other microorganisms (other than fermentative bacteria) as well, there is the need of actual energy-yielding pathway i.e. aerobic pathway in which acetyl-CoA is produced instead of alcohol or lactate. Acetyl CoA thus obtained is then utilized to run TCA cycle from where there is significantly large yield of energy with the assistance of electron transport chain.

In the step of conversion of pyruvate to acetyl-CoA, there is oxidative decarboxylation of pyruvate. The pyruvate is oxidized and decarboxylated (release of CO2) with the aid of enzyme, pyruvate dehydrogenase complex. In this course of the reaction, there is the reduction of NAD+ to NADH + H⁺. This step is the connecting link between glycolysis and TCA cycle. Reaction occurs as shown below:

Oxaloacetate Formation:

Formation of oxaloacetate at normal condition does not occur among organisms. In some organs of higher organisms like brain, heart, kidneys, Red Blood Cells etc., there is a continuous requirement of glucose as metabolic fuel. During fasting or starvation, there will be no external supply of glucose and the supply of it to those continuously working organs may be hindered ,but still the organs work for some times mean to say even for some days. Question is how those organ get glucose in such critical conditions?

Well, the answer is hidden in the topic we are talking about. Here in this course of reaction ultimate way of formation of oxaloacetate takes place (not from TCA cycle) and this oxaloacetate undergo gluconeogenesis utilizing the hepatic glycogen and form glucose molecule that can now operate the functioning of organs.

Pyruvate is converted into oxaloacetate in direct pathway by the carboxylation of it with the assistance of enzyme, pyruvate carboxylase. This is the single step reaction and can be represented as below: