Lactate dehydrogenase Lactic acid

An important point to note is that this the above reaction produces lactate, not lactic acid. Nonetheless, protons are produced in glycolysis but in another reaction (Appendix 6.5). Consequently, the two end-products are lactate plus protons, which can be described as lactic acid. Despite this discussion, it can be argued that lactate dehydrogenase is not the terminal reaction of glycolysis, since the lactate plus protons have to be transported out of the cell into the interstitial space. This requires a transporter protein, which transports both lactate and protons across the plasma membrane and out of the cell. 

NS), respectively, cytochrome oxidase decreased 9%(NS). Treatment-related effects in wmn muscle citrate synthetase decreased 19% (NS), cytochrome oxidase increased 23% (NS), muscle lactate and lactic acid dehydrogenase affected. Subjects reported no adverse health effects after exposure. 

An inhibitor for lactate dehydrogenase would block the formation of lactic acid or lactate, the main distinguishing feature of cancer cell metabolism. This would alternately favor the normal oxidation of pyruvic acid or pyruvate via the tricarbox-yhc acid cycle. As a quahlication, cancer cells also apparently undergo a degree of oxidative metabohsm, though the conversion to lactate or lactic acid occurs to a much greater extent. 

Enzyme catalyzed reductions of carbonyl groups are more often than not com pletely stereoselective Pyruvic acid for example is converted exclusively to (5) (+) lactic acid by the lactate dehydrogenase NADH system (Section 15 11) The enantiomer... 

Lactic acid Lactate dehydrogenase Ferricyanide ions Platinum... 

EC 1.1.1.14 L-Iditol dehydrogenase EC 1.1.1.27 Lactate dehydrogenase L-Iditol + NAD + t L-sorbose + NADH Lactic acid + NAD+ pyruvic acid + NADH + H + — SM... 

The mechanism of toxicity of ethylene glycol involves metabolism, but unlike previous examples, this does not involve metabolic activation to a reactive metabolite. Thus, ethylene glycol is metabolized by several oxidation steps eventually to yield oxalic acid (Fig. 7.84). The first step is catalyzed by the enzyme alcohol dehydrogenase, and herein lies the key to treatment of poisoning. The result of each of the metabolic steps is the production of NADH. The imbalance in the level of this in the body is adjusted by oxidation to NAD coupled to the production of lactate. There is thus an increase in the level of lactate, and lactic acidosis may result. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation, glucose metabolism, Krebs cycle, protein synthesis, RNA synthesis, and DNA replication. 

In the Korkes and Ochoa (11) mechanism proposed for the malo-lactic reaction (see top of next page), pyruvic acid is either a short-lived, fleeting intermediate, or it is bound to malic enzyme so that as soon as it is formed by the enzyme, it is converted to lactic acid by lactate dehydrogenase. [Both malic enzyme ( malic ) and malate dehydrogenase (de-... 

They stated further that, the new adaptive enzyme catalyzing Reaction 3 appears to be similar to the malic enzyme of pigeon liver, although strictly DPN (instead of TPN)-specific. The coenzyme specificity explains the ready occurrence of Reaction 1. Therefore, the authors showed that exogenous NAD was required for the overall reaction (malic acid -> lactic acid), but because this activity was measured manometrically, they never demonstrated the formation of reduced NAD. Similarly, they did not attempt to show that pyruvic acid was the intermediate between L-malic acid and lactic acid. Instead, the formation of pyruvic acid was inferred from the NAD requirement and because the malic acid dissimilation activity remained constant during purification while the lactate dehydrogenase activity decreased (14). In fact, attempts to show any appreciable amounts of pyruvic acid intermediate failed (22). 

A requirement for all fermentations is the existence of a mechanism for coupling ATP synthesis to the fermentation reactions. In the lactic acid and ethanol fermentations this coupling mechanism consists of the formation of the intermediate 1,3-bisphosphoglycerate by the glyceraldehyde 3-phosphate dehydrogenase (Fig. 10-3, step a). This intermediate contains parts of both the products ATP and lactate or ethanol. 

Dehydrogenases often act primarily to reduce a carbonyl compound rather than to dehydrogenate an alcohol. These enzymes may still be called dehydrogenases. For example, in the lactic acid fermentation lactate is formed by reduction of pyruvate but we still call the enzyme lactate dehydrogenase. In our bodies this enzyme functions in both directions. However, some enzymes that act mainly in the direction of reduction are called reductases. An example is aldose reductase, a member of a family of aldo-keto reductases71 73 which have (a / P)8-barrel structures.74 76... 

Some enzymes contain bound NAD+ which oxidizes a substrate alcohol to facilitate a reaction step and is then regenerated. For example, the malolactic enzyme found in some lactic acid bacteria and also in Ascaris decarboxylates L-malate to lactate (Eq. 15-12). This reaction is similar to those of isocitrate dehydrogenase,110-112 6-phosphogluconate dehydrogenase,113 and the malic enzyme (Eq. 13-45)114 which utilize free NAD+ to first dehydrogenate the substrate to a bound oxoacid whose (3 carbonyl group facilitates decarboxylation. Likewise, the bound NAD+ of the malolactic... 

Deficiency of pyruvate dehydrogenase is the most frequent cause of lactic acidemia ac Since this enzyme has several components (Fig. 15-15), a number of forms of the disease have been observed. Patients are benefitted somewhat by a high-fat, low-carbohydrate diet. Transient lactic acidemia may result from infections or from heart failure. One treatment is to administer dichloroacetate, which stimulates increased activity of pyruvate dehydrogenase, while action is also taken to correct the underlying illness.d Another problem arises if a lactate transporter is defective so that lactic acid accumulates in muscles.6... 

Reduction of achiral precursors is often used to produce chiral products. The advantage of this approach is that the theoretical yield of product is 100% compared to the 50% theoretical maximum for the resolution of racemates. Cross-linked crystals of lactate dehydrogenase have been used to prepare L-lactic acid from pyruvic acid in an electrolytic cell. The LDH CLCs maintained constant... 

---