Lactate, formed by the action of lactate dehydrogenase , is the final product of anaerobic glycolysis in eukaryotic cells (Figure 8.21). The formation of lactate is the major fate for pyruvate in lens and cornea of the eye, kidney medulla, testes, leukocytes and red blood cells, because these are all poorly vascularized and/or lack mitochondria. 1. Lactate formation in muscle: In exercising skeletal muscle, NADH production (by glyceraldehyde 3-phosphate dehydrog enase and by the three NAD + -linked dehydrogenases of the citric acid cycle, see p. 112) exceeds the oxidative capacity of the respiratory chain. This results in an elevated NADH/NAD + ratio, favoring reduction of pyruvate to lactate. Therefore, during intense exer- cise, lactate accumulates in muscle, causing a drop in the intra- cellular pH, potentially resulting in cramps. Much of this lactate eventually diffuses into the bloodstream, and can be used by the liver to make glucose (see p. 118). 2. Lactate consumption: The direction of the lactate dehydrog enase 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 con- verted to glucose by gluconeogenesis or oxidized in the TCA cycle. Heart muscle exclusively oxidizes lactate to CO 2 and H 2 O via the citric acid cycle.