Lactate dehydrogenase glycolysis

Hanson, A.D. Jacobsen, J.V. (1984). Control of lactate dehydrogenase, lactate glycolysis and a-amylase of O2 deficit in barley aleurone layers. Plant Physiology, 75, 566-72. 

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

Figure 6.1 Pathways involved in glucose oxidation by plant cells (a) glycolysis, (b) Krebs cycle, (c) mitochondrial cytochrome chain. Under anoxic conditions. Reactions 1, 2 and 3 of glycolysis are catalysed by lactate dehydrogenase, pyruvate decarboxylase and alcohol dehydrogenase, respectively. ATP and ADP, adenosine tri- and diphosphate NAD and NADHa, oxidized and reduced forms of nicotinamide adenine dinucleotide PGA, phosphoglyceraldehyde PEP, phosphoenolpyruvate Acetyl-CoA, acetyl coenzyme A FP, flavoprotein cyt, cytochrome e, electron. (Modified from Fitter and Hay, 2002). Reprinted with permission from Elsevier...

In cells that lack mitochondria, or dnring hypoxia in aerobic tissues, NADH is oxidised to NAD+ in a reaction in which pyruvate is reduced to lactate, catalysed by lactate dehydrogenase (i.e. anaerobic glycolysis). 

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. 

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 mitochondrial inner membrane has no transport system for NAD+ or NADH. In animal cells, most of the NADH that must be oxidized by the respiratory chain is generated in the mitochondrial matrix by the TCA cycle or the oxidation of fatty acids. However, NADH also is generated by glycolysis in the cytosol. If 02 is available, it clearly is advantageous to reoxidize this NADH by the respiratory chain, rather than by the formation of lactate or ethanol as described in chapter 12. This is evident from the findings that approximately 2.5 molecules of ATP can be formed for each NADH oxidized in the mitochondria, whereas no ATP is made when NADH is oxidized by the cytosolic lactate dehydrogenase or alcohol dehydrogenase. 

The ANLSH challenged the classic view [2, 3]. It postulates compartmentaliza-tion of brain lactate metabolism between neurons and astrocytes the activity-induced uptake of glucose takes place predominantly in astrocytes, which metabolize glucose anaerobically. Lactate produced from anaerobic glycolysis in astrocytes is then released from astrocytes and provides the primary metabolic fuel for neurons. The increased lactate in the neurons is converted to pyruvate via lactate dehydrogenase (LDH), which enters the TCA cycle, and increases ATP production in the neurons via oxidative phosphorylation (Fig. 8.1). This view is highly discussed, pro [4, 5]) and contra [1, 6]. 

Lactate dehydrogenase (LDH) catalyses the reversible terminal reaction in glycolysis which results in the formation of lactic acid. It is present in a number of cestodes (Table 5.5), which is not surprising as most species excrete lactate (Table 5.4). Even S. solidus, which produces mainly acetate and propionate, has an active... 

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