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Fate of Pyruvate under different conditions (Lecture-1)
1. Ethanol is formed from pyruvate in yeast and several other microorganisms. The first step is the decarboxylation of pyruvate. This reaction is catalyzed by pyruvate decarboxylase, which requires the coenzyme thiamine pyrophosphate. This coenzyme, derived from the vitamin thiamine (B1), also participates in reactions catalyzed by other enzymes. The second step is the reduction of acetaldehyde to ethanol by NADH, in a reaction catalyzed by alcohol dehydrogenase. This process regenerates NAD+.
Reaction 1- showing the conversion of pyruvate to Ethanol The net result of this anaerobic process is:
The conversion of glucose into ethanol is an example of alcoholic fermentation. NADH generated by the oxidation of glyceraldehyde 3-phosphate is consumed in the reduction of acetaldehyde to ethanol. Thus, there is no net oxidation-reduction in the conversion of glucose into ethanol (Reaction-1). The ethanol formed in alcoholic fermentation provides a key ingredient for brewing and winemaking.
2. Lactate is formed from pyruvate in a variety of microorganisms in a process called lactic acid fermentation. The reaction also takes place in the cells of higher organisms when the amount of oxygen is limiting, as in muscle during intense activity. The reduction of pyruvate by NADH to form lactate is catalyzed by lactate dehydrogenase (Reaction-2)
Reaction-2- showing the conversion of pyruvate to Lactate The overall reaction in the conversion of glucose into lactate is:
As in alcoholic fermentation, there is no net oxidation-reduction. The NADH formed in the oxidation of glyceraldehyde 3-phosphate is consumed in the reduction of pyruvate. The regeneration of NAD + in the reduction of pyruvate to lactate or ethanol sustains the continued operation of glycolysis under anaerobic conditions.
3. Acetyl co A – Only a fraction of the energy of glucose is released in its anaerobic conversion into ethanol or lactate. Much more energy can be extracted aerobically by means of the citric acid cycle and the electron-transport chain. The entry point to this oxidative pathway is acetyl coenzyme A (acetyl CoA), which is formed inside mitochondria by the oxidative decarboxylation of pyruvate.
The NAD+ required for this reaction and for the oxidation of glyceraldehyde 3-phosphate is regenerated when NADH ultimately transfers its electrons to O2 through the electron-transport chain in mitochondria. The reaction is catalyzed by a multienzyme complex called Pyruvate dehydrogenase complex.
4. Oxaloacetate- Pyruvate can be converted to oxaloacetate. Mitochondrial pyruvate carboxylase catalyzes the carboxylation of pyruvate to oxaloacetate, an ATP-requiring reaction in which the vitamin biotin is the coenzyme. Biotin binds CO2 from bicarbonate as carboxybiotin prior to the addition of the CO2 to pyruvate.
Reaction-3– showing the conversion of pyruvate to Oxaloacetate.
The Oxaloacetate can be subsequently used for the synthesis of Aspartate, phosphoenol pyruvate or be utilized in the TCA cycle depending upon the need of the cell.
5. Alanine- Pyruvate can be transaminated to form Alanine as per need.
Reaction-4- showing the conversion of Pyruvate to Alanine by transamination. The reaction is catalyzed by ALT (Alanine transferase also called SGPT-Serum glutamate alanine transaminase) This reaction is important for the catabolism and synthesis of nonessential amino acids
6. Malate- Pyruvate can be directly converted to oxaloacetate or it is first carboxylated to malate and then decarboxylated to form oxaloacetate (Figure-1). These two reactions are called CO2 filling up reactions or Anaplerotic reactions. They provide oxaloacetate when there is sudden influx of Acetyl co A in the TCA cycle.
Figure-1-showing the formation of Oxaloacetate from Pyruvate.
Thus Pyruvate can be metabolized through several pathways as per availability of O2 or requirement of the cell for a specific metabolite.
For details of PDH complex- see the next post.
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