The Fates of Pyruvate

The production of two molecules of pyruvate from one molecule of glucose occurs in virtually all cells. This process has three important characteristics (1) no oxygen is required (2) two molecules of ADP are phosphorylated by substrate-level phosphorylation and (3) two molecules of NAD+ are reduced. The subsequent fate of pyruvate in a particular cell depends on conditions related to these 

Fructose 6-phosphate Fructose, . 1,6-bisphosphate 1 Phosphoenol- pyruvate qaTPyruva,c 1  

Question Why must the NADH produced in glycolysis be oxidized to NAD + and thus be recycled  

NAD+ is required by glyceraldeyde 3-phosphate dehydrogenase (Step 6) therefore, NAD + is essential for this step and for glycolysis to proceed. Cells do not contain high concentrations of either NAD+ or NADH there must be mechanisms available for their interconversion so that each is available for the reactions in which it takes part. 

A further criterion governing the fate of pyruvate is the type of cell in which it is formed, since some cells (e.g., red blood cells) lack the metabolic capability to carry out the complete oxidation of pyruvate to C02. 

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Acetyl-CoA is a critical regulator of the fate of pyruvate it allosterically inhibits pyruvate dehydrogenase and stimulates pyruvate carboxylase (see Fig. 15-20). In these ways acetyl-CoA prevents it own further production from pyruvate while stimulating the conversion of pyruvate to oxaloacetate, the first step in gluconeo-genesis. 

What determines the fate of pyruvate produced in muscle from amino acid metabolism SOLUTION... 

The fate of pyruvate formed by glycolysis differs among species, and within the same species depending on the level of oxygen available for further oxidation of the products of glycolysis. 

Let s turn now to the fate of pyruvate in aerobic tissues. Pyruvate must first be transported into the mitochondria, where it can then be oxidized to give acetyl CoA, which can then be used to make fat for storage or it can be further oxidized to carbon dioxide via the Kreb s TCA Cycle. 

The sequence of reactions from glucose to pyruvate is similar in most organisms and most types of cells. In contrast, the fate of pyruvate is variable. Three reactions of pyruvate are of primary importance conversion into ethanol, lactate, or carbon dioxide (Figure 16.9). The first two reactions are fermentations that take place in the absence of oxygen. In the presence of... 

The fate of pyruvate depends on the route used for NADH oxidation. If NADH is reoxidized in a shuttle system, pyruvate can be used for other pathways, one of which is oxidation to acetyl-CoA and entry into the TCA cycle for complete oxidation. Alternatively, in anaerobic glycolysis, pyruvate is reduced to lactate and diverted away from other potential pathways. Thus, the use of the shuttle systems allows for more ATP to be generated than by anaerobic glycolysis by both oxidizing the cytoplasmically derived NADH in the electron transport chain and by allowing pyruvate to be oxidized completely to CO2. 

There are three important conclusions to be drawn from this equation (1) No oxygen is required for the reaction, (2) 2 mol of ATP are produced by substrate level phosphorylation, and (3) 2 mol of NAD are reduced to NADH. The fate of pyruvate depends on all three of these considerations, i.e., what mechanisms are available for the oxidation of NADH, what levels of ATP are present in the cell, and what is the concentration of oxygen in the cell. 

Problem 22.14. What controls the fate of pyruvate produced by glycolysis ... 

As glucose is oxidized to pyruvate in glycolysis, NAD is reduced to NADH. The need for a continuous supply of NAD for glycolysis is a key to understanding the fates of pyruvate. 

Compare the fate of pyruvate in the body under (a) aerobic conditions and (b) anaerobic conditions. 

Compare the fate of pyruvate (a) in the body under aerobic conditions, (b) in the body under anaerobic conditions, and (c) in alcoholic fermentative microhes under anaerobic conditions. 

Quantitatively the fate of pyruvate or other 3-carbon fragments in the light is far more important than in the dark (see Chap. 3.1.6). The critical question is whether the pyruvate is completely oxidized to CO2 prior to carbon reassimilation or if it is quantitatively converted to carbohydrates, perhaps by glycolytic reversal. Early experiments clearly showed that malate was not converted directly to carbohydrate (Ranson and Thomas, 1960). 

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