CHAPTER 22: Unit 5. Pathways for Pyruvate

Pyruvate is a key intersection in the network of metabolic pathways. Pyruvate can be converted into carbohydrates via gluconeogenesis, to fatty acids or energy through acetyl-CoA, to the amino acid alanine, and to ethanol. Therefore, it unites several key metabolic processes.

The pyruvate produced from glucose can enter pathways that continue to extract energy. The available pathway depends on whether there is sufficient oxygen in the cell. Under aerobic conditions, oxygen is available to convert pyruvate to acetyl coenzyme A (Acetyl CoA) and CO₂. When oxygen levels are low, pyruvate is reduced to lactate. In yeast cells pyruvate is reduced to ethanol and CO₂.

Pyruvate sits at an intersection of key pathways of energy metabolism. It is the end product of glycolysis and the starting point for gluconeogenesis and can be generated by transamination of alanine. It can be converted by the pyruvate dehydrogenase complex to acetyl CoA (Reed and Hackert 1990) which can enter the TCA cycle or serve as the starting point for the syntheses of long chain fatty acids, steroids, and ketone bodies depending on the tissue and metabolic state in which it is formed. It also plays a central role in balancing the energy needs of various tissues in the body. Under conditions in which oxygen supply is limiting, e.g., in exercising muscle, or in the absence of mitochondria, e.g., in red blood cells, re-oxidation of NADH produced by glycolysis cannot be coupled to generation of ATP. Instead, re-oxidation is coupled to the reduction of pyruvate to lactate. This lactate is released into the blood, and is taken up primarily by the liver, where it is oxidized to pyruvate and can be used for gluconeogenesis.

Reference:
https://www.youtube.com/watch?v=wI2RC3_Y1KA

Aerobic Conditions of pyruvateUnder aerobic conditions, pyruvate is oxidatively decarboxylated to yield acetyl-CoA in a reaction catalyzed by the enzyme pyruvate dehydrogenase (PDH.When there is enough oxygen available to the cell, pyruvate crosses the mitochondrial membrane and is quickly converted to Acetyl CoA. Acetyl CoA enters the Citric Acid Cycle where CoA is removed, and the acetate is added to a 4 carbon molecule to make a 6 carbon molecule called “Citric Acid.” As the biochemical steps of the Citric Acid Cycle continue (See figure 9), 2 more carbons are lost as CO2 and so ultimately all the carbons of pyruvate are lost as CO2. After 2 pyruvates complete the citric acid cycle, all the carbons of the original Glucose molecule have been released as CO2.

The reaction to the above occurs in the matrix of the mitochondria. Pyruvate is the end product of glycolysis (which occurs in the cytoplasm). Pyruvate is moved into the mitochondria where it reacts with the enzyme “pyruvate dehydrogenase”. The result of this reaction is the loss of a carbon from the 3 carbons pyruvate (lost in the form of CO2). Also, coenzyme A is attached to the remaining two carbons. The two-carbon molecule remaining after CO2 is lost is called acetate. When acetate is joined to CoA, it is called Acetyl CoA. Acetyl CoA will be used in the first step of the citric acid cycle. Anaerobic Conditions of pyruvateWhen we engage in strenuous exercise, the oxygen stored in our muscle cells is quickly depleted. Under anaerobic conditions, pyruvate remains in the cytosol where it is reduced to lactate. The product NAD+ is used to oxidize glyceraldehyde-3-phosphate in the glycolysis pathways, which produces a small but needed amount of ATP.