Lactate production

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

In vivo, patients treated with AZT develop a mitochondrial myopathy with mitochondrial DNA depletion, deficiency of cytochrome c oxidase (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion (Lewis and Dalakas 1995 Dalakas 2001). Clinically, the patient presents with fatigue, myalgia, muscle weakness, wasting and elevated serum creatine kinase. Muscle biopsy shows ragged red fibers , the characteristic histopathologic changes of mitochondrial myopathy, cansed by subsarcolemmal accumulation of mitochondria (Lewis and Dalakas 1995). 

Kelly D. and King T.P. (1991). The influence of lactation products on the temporal expression of histo-blood group antigens in the intestines of suckling pigs lectin histochemical and immunohistochemical analysis . Histochem J, 23, 55-60. 

Paul I wanted to come back to the issue of mitochondria and Ca2+. I happen to have friends on both sides of that issue. We have been promoting the idea, which seems to work in a variety of tissues, that subsarcolemmal space is highly populated by glycolytic enzymes. This is true in skeletal muscles also. One of the first things seen with ouabain is that it kills the lactate production without touching oxygen... 

Marroquin, L.D., dykens, J.D., Nadanadva, S Jamieson, J. and Will, Y. (2008) Biguanide-induced mitochondrial dysfunction increases lactate production and reduces viability of aerobically poised HepG2 and human hepatocytes in culture. The Toxicologist, 2008, 903. 

The result of formate accumulation is metabolic acidosis. However, at later stages, the acidosis may also involve the accumulation of other anions such as lactate. This may be a result of inhibition of cytochrome oxidase and hence of mitochondrial respiration, tissue hypoxia due to reduced circulation of blood, or an increase in the NADH/NAD ratio. The acidosis that results from methanol poisoning will result in more formic acid being in the nonionized state and hence more readily able to enter the CNS. This will cause central depression and hypotension and increased lactate production. This situation is known as the "circulus hypoxicus."... 

Morgan, D. B., Monod, A., Russell, R. G. G., Fleisch, H. Influence of dichlormethylene diphosphonate (C12MDP) and calcitonin on bone resorption, lactate production and phosphate and pyrophosphatase content of mouse calvaria treated with parathyroid hormone in vitro. Calc. Tiss. Res. 13, 287 (1973)... 

Holten. C.H. A Muller and D Rehhiuder- ta. iii And. International Research Aw i nioii Verlag Cliemie. Copenhagen. Denmark. 1971 Lanie Actd and Lactates, product bulletin. Purac Inc.. Arlington Heights. tL. I ISO... 

Mechanism and susceptibility factors Biguanides in high doses inhibit the oxidation of carbohydrate substrates by affecting mitochondrial function. Anoxidative carbohydrate metabolism stimulates the production of lactate. High lactate production leads to lactic acidosis (type B) with a low pH (<6.95). Hyperlactatemia was common in patients taking buformin, even without alcoholism or impaired liver, kidney, or cardiac function (70). 

The performance of the F-MF-ED system was also assessed in the case of lactate fermentation from xylose (Nomura et al., 1988). Starting with 50 kg of xylose per m3, the conventional or combined system allowed full exhaustion of the carbon source after 60 or 32 hours, respectively. By further increasing the initial xylose concentration to 80 kg/m3, both systems resulted in less (50 kg/m3) or more (75 kg/m3) consumption of xylose, respectively. Moreover, the simultaneous removal of microbial metabolites (lactate and acetate) via ED increased both lactate production and xylose consumption rates. 

Simultaneous L-lactic acid fermentation (by Rhizopus oryzae immobilized in calcium alginate beads) and separation was carried out using a three-phase fluidized-bed bioreactor as a fermenter (F), an external electrodialyzer as a separator, and a pump to recycle the fermentation broth between the bioreactor and the separator. In this way, the experimental specific lactate productivity and yield practically coincided with those obtained in the CaC03-buffered fermentation process (Xuemei et al., 1999), thus confirming the capability of the combined system to alleviate product inhibition without any addition of alkali or alkali salts. It was also shown that the adoption of ED-F for the production of inoculum reduced variability in inoculum quality, thus shortening the length of the lag phase of L-lactate production practically to zero as compared to that observed using an inoculum... 

Lactic acid formation occurred to a different extent when paper sludge hydrolysate was used. Although the same batch of hydrolysate was used for all experiments under identical conditions, lactate production was observed from the early stage (Fig. 2, condition D2) of the fermentation or lactate was only found in the fermentation broth in the very late phase of the process (condition Dl). 

Moss EJ, Cook MW, Thomas LV, et al. 1988. The effect of mono-(2-ethylhexyl) phthalate and other phthalate esters on lactate production by Sertoli cells in vitro. Toxicol Lett 40 77-84. 

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