Lactate from pyruvate

Fig. 5. Coupled electrochemical process for the formation of D-lactate from pyruvate (l-LDH = L-lactate dehydrogenase)...

When complex I is defective, there is an excess of cellular NADH, which pushes the lactate dehydrogenase to form lactate from pyruvate (anaerobic glycolysis). This results in higher than normal utilization of glucose, causing hypoglycemia. Because succinate is oxidized at the complex II level, its oxidation is not affected. 

There are many applications involving FDH from C. boidinii. In 1980, Shaked and Whitesides published the first example to demonstrate the regeneration of a coenzyme in a preparative synthesis by coupling this enzyme with a simple NADH-consuming reaction, the production of D-lactate from pyruvate (Fig. 3) [41]. 

Fig. 3 Preparation of D-lactate from pyruvate catalyzed by d-LDH (D-lactate dehydrogenase) using formate/FDH for the regeneration of NADH...

L-Lactate dehydrogenase (l-LDH, EC 1.1.1.27) catalyzes the reduction of pyruvate to (S)-lactate with a simultaneous oxidation of NADH. l-LDH is found in all higher organisms. There are two kinds of l-LDHs enzymes from one group are activated by fructose 1,6-diphosphate while the other group stays independent [71]. l-LDH is highly selective for pyruvate, short-chain 2-keto acids and phenylpyruvic acid [80]. All bacterial NAD+-dependent LDHs form lactate from pyruvate in vivo, and there is no evidence at all that they catalyze the other direction as well. The equilibrium constant lies far on the direction of lactate formation, and thus the reaction catalyzed by bacterial LDHs can be considered almost irreversible. LDHs from some lacto-bacilli like Lactobacillus fermentum or L. cellobiosus show no or just poor reaction with lactate [71], whereas mammalian LDHs can be considered as reversible [71]. Well characterized l-LDHs are summarized in Table 2. 

In a different approach, instead of methyl viologen, the organic disulfide dithiothrei-tol was cathodically reduced to give the bis-thiol, which consecutively reduces the disulfide bridge within the lipoamide of the lipoamide dehydrogenase. This is followed by the NADH regeneration by the reduced LipDH in combination with the production of enzyme L-lactate dehydrogenase for the production of L-lactate from pyruvate. Both enzymes were immobihzed within a poly (acrylamide) gel [50]. 

A promising technique uses NAD-dependent hydrogenases to catalyze the electron transfer between a platinum cathode and NAD" ". This approach was applied to the synthesis of lactate from pyruvate [9,38,55] or L-glutamate from a-ketoglutarate in an analytical thin-layer cell with 50 pi volume at a potential of —0.7 V vs. SCE (Fig. 11). Within 1 h, a 44.8 mM concentration of the product was obtained at a turnover frequency of 448/h [56]. 

B. Lactate dehydrogenase produces lactate from pyruvate when NADH levels are high. 

Figure 14 Two possible routes for the formation of L-lactyl-phosphate. The top of the figure (a) shows the pathway to lactate from pyruvate catalyzed by lactate dehydrogenase and observed in bacteria and eukaryotes. The bottom pathway (b) is that observed in the methanogens.

In muscle, lactate dehydrogenase produces lactate from pyruvate, whereas in the heart it preferentially synthesizes pyruvate from lactate. Explain how this is possible. 

Glycolysis takes place in the cell cytoplasm, whereas the decarboxylation of pyruvate and the subsequent oxidation of acetyl-coenzyme A via the tricarboxylic acid cycle take place in the mitochondrial matrix. Under anaerobic conditions, oxygen is not available for the oxidation of reduced NAD by oxidative phosphorylation, in order to allow the release of a small amount of energy by continuing the breakdown of glucose to pyruvate, reduced NAD must be converted to the oxidised form, if not, step 7 of Fig. 9.4 will not take place and energy production will be blocked. Oxidation of reduced NAD may be achieved under such conditions by the formation of lactate from pyruvate in the presence of lactate dehydrogenase ... 

She found that this cooked up some intriguing molecules. In the presence of metal sulfides, pyruvate gains complexity, picking up sulfurs, nitrogens, or even other pyruvates to form a full slate of complex molecules. Some minerals make the metabohc molecule lactate from pyruvate, and some even make the amino acid alanine, which is pyruvate plus nitrogen. Proteins make both of these molecules from pyruvate today. 

Mimicry of In Vivo Coenzyme Regeneration Processes Electroenzymatic Production of Lactate from Pyruvate... 

The reaction scheme is composed of a three-reaction sequence (1) the NADH-dependent enzymatic (lactate dehydrogenase LDH) synthesis of lactate from pyruvate (2) the regeneration of NADH from NAD+ and enzymatic (lipoamide dehydrogenase LipDH) reaction with the mediator (methyl viologen) ... 

Electro-Enzymatic Production of Lactate from Pyruvate References.7-14... 

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