Lactate dehydrogenase gluconeogenesis

FIGURE 14-19 Alternative paths from pyruvate to phospho-enolpyruvate. The path that predominates depends on the glucogenic precursor (lactate or pyruvate). The path on the right predominates when lactate is the precursor, because cytosolic NADH is generated in the lactate dehydrogenase reaction and does not have to be shuttled out of the mitochondrion (see text). The relative importance of the two pathways depends on the availability of lactate and the cytosolic requirements for NADH by gluconeogenesis. 

Lactate consumption The direction of the lactate dehydrogenase reaction depends on the relative intracellular concentrations of pyruvate and lactate, and on the ratio of NADH/NAD+ in the cell. For example, in liver and heart, the ratio of NADH/NAD+ is lower than in exercising muscle. These tissues oxidize lactate (obtained from the blood) to pyruvate. In the liver, pyruvate is either converted to glucose by gluconeogenesis or oxidized in the TCA cycle. Heart muscle exclusively oxidizes lactate to CO2 and H20 via the citric acid cycle. 

Figure 18.1 Glucose and lactate traffic in the human organism. Abbreviations glu, glucose gly, glycogen lac, lactate pyr, pyruvate Krebs, Krebs cycle. Pyr is converted to lac, and vice versa, through lactate dehydrogenase (LDH). Although the action of LDH is reversible, the conversions shown indicate only the more prevalent direction. Pyr can be converted to glu via the gluconeogenesis pathway in the liver. Dotted arrow indicates a minor pathway.

The second reason for lack of development of L-lactic acidosis is the saturation of alcohol dehydrogenase, which results in a constant rate of lactate production. Due to removal of L-lactate by gluconeogenesis, a further increase in lactate levels is not possible after saturation of metabolism. 

Lactate is released by red blood cells and other cells that lack mitochondria or have low oxygen concentrations. In the Cori cycle, lactate is released by skeletal muscle during exercise (Figure 8.8). After lactate is transferred to the liver, it is reconverted to pyruvate by lactate dehydrogenase and then to glucose by gluconeogenesis. 

See also Relationship of Gluconeogenesis to Glycolysis, Gluconeogenesis, Lactate Dehydrogenase, Pyruvate, Lactate, Oxaloacetate, L-Malate. 

Gluconeogenesis involving lactate is especially important. As might be expected, this process follows a separate and different pathway from glycolysis. During active exercise, lactate levels increase in muscle tissue, and the compound diffuses out of the tissue into the blood. It is transported to the liver, where lactate dehydrogenase, the enzyme that catalyzes lactate formation in muscle, converts it back to pyruvate ... 

Figure 7-1. Pathways of fuel metabolism and oxidative phosphorylation. Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis, or for oxidation to acetyl-CoA by the pyruvate dehydrogenase complex (PDC). Long-chain fatty acids are transported into mitochondria, where they undergo [ -oxidation to ketone bodies (liver) or to acetyl-CoA (liver and other tissues). Reducing equivalents (NADH, FADII2) are generated by reactions catalyzed by the PDC and the tricarboxylic acid (TCA) cycle and donate electrons (e ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (Complex 0 or at succinate ubiquinone oxidoreductase (Complex ID- Cytochrome c oxidase (Complex IV) catalyzes the reduction of molecular oxygen to water, and ATP synthase (Complex V) generates ATP fromADP Reprinted with permission from Stacpoole et al. (1997).

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