Pyruvate to lactate

The active form of lactate dehydrogenase (mass 144 kDa) is a tetramer consisting of four subunits (1). Each monomer is formed by a peptide chain of 334 amino acids (36 kDa). In the tetramer, the subunits occupy equivalent positions (1) each monomer has an active center. Depending on metabolic conditions, LDH catalyzes NADH-de-pendent reduction of pyruvate to lactate, or NAD -dependent oxidation of lactate to pyruvate (see p. 18). 

Figure 6-1. The steps of glycolysis. Feedback inhibition of glucose phosphorylation by hexokinase, inhibition of pyruvate kinase, and the main regulatory, rate-limiting step catalyzed by phosphofructoki-nase (PFK-I) are indicated, pyruvate formation and substrate-level phosphorylation are the main outcomes of these reactions. Regeneration of NAD occurs by reduction of pyruvate to lactate during anaerobic glycolysis.

When animal tissues cannot be supplied with sufficient oxygen to support aerobic oxidation of the pyruvate and NADH produced in glycolysis, NAD+ is regenerated from NADH by the reduction of pyruvate to lactate. As mentioned earlier, some tissues and cell types (such as erythrocytes, which have no mitochondria and thus cannot oxidize pyruvate to C02) produce lactate from glucose even under aerobic conditions. The reduction of pyruvate is catalyzed by lactate dehydrogenase, which forms the l isomer of lactate at pH 7 ... 

The different LDH isozymes have significantly different values of Vmax and KM, particularly for pyruvate. The properties of LDH4 favor rapid reduction of very low concentrations of pyruvate to lactate in skeletal muscle, whereas those of isozyme LDHx favor rapid oxidation of lactate to pyruvate in the heart. 

Figure 17-7 Outline of the glycolysis pathway by which hexoses are broken down to pyruvate. The ten enzymes needed to convert D-glucose to pyruvate are numbered. The pathway from glycogen using glycogen phosphorylase is also included, as is the reduction of pyruvate to lactate (step 11). Steps 6a-7, which are involved in ATP synthesis via thioester and acyl phosphate intermediates, are emphasized. See also Figures 10-2 and 10-3, which contain some additional information.

The final form of metabolic regulation is effected by the use of iso-enzymes, which are multiple forms of an enzyme. For example, lactate dehydrogenase exists in five forms in a rat. They differ in primary structure and have different isoelectric points, but they all catalyse the reversible reduction of pyruvate to lactate. 

Regeneration of NAD+ by reduction of pyruvate to lactate. Because NAD+ is a necessary participant in the oxidation of glyceraldehyde-3-phosphate to glycerate-l,3-bisphosphate, glycolysis is possible only if there is a way by which NADH can be reoxidized. 

Lactate dehydrogenase (LDH, E.C. 1.1.1.27) catalyzes the reduction of pyruvate to lactate using NADH as a cofactor ... 

Figure 4.10 Lactic acid fermentation in which the conversion of pyruvate to lactate is coupled with glycolysis to produce energetic ATP.

In the presence of pyruvate kinase, pyruvate and ATP may be formed with the subsequent conversion of pyruvate to lactate (or, exceptionally, other... 

Hochachka, P.W, C. Stanley, D.C. McKenzie, A. Villena, and C. Monge (1992). Enzyme mechanisms for pyruvate-to-lactate flux attentuation A study of Sherpas, Quechuas, and hummnigbirds. Int. J. Sport Med. 13 S119-S123. 

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