Lactate accumulation

Lactate Accumulates Under Anaerobic Conditions in Animal Tissues... 

The lactate accumulation during intense anaerobic exercise was implicated as a possible fatigue factor as early as the beginning of this century (Fletcher and Hopkins, 1907). A detailed presentation of the role of H" and Pi in the contractile process has been presented in the section on fatigue in isolated fibers. 

Lactate accumulation in muscle can cause cramp not a good thing to happen to the heart Cardiac LD has a low Km for lactate ensuring that the concentration does not rise too high. Also, by converting lactate into pyruvate, more fuel can be made available for the heart muscle in times of greater need, for example exercise. 

Generally, lactate concentrations below 20 mM are considered not to show any negative effects (Table 4.1). There are several actions that can be performed in a culture process to reduce lactate accumulation, and these have already been mentioned. 

These hypoxia acclimation processes take days to weeks to settle down at new steady states. However, when complete, hypoxia acclimations are able to compensate for the 02 deficit of hypoxia better than acute adjustments. For example, after acclimation in lowlanders, the V02max is still affected by hypoxia, but to a lesser degree than previously. There is less energy deficit due to 02 lack and less postexercise blood lactate accumulation. 

Natale J. A. and D Alecy L. G. (1989) Protection from cerebral ischemia by brain cooling without reduced lactate accumulation in dogs. Stroke 20,770-777. 

Addition of oxygen to cells metabolizing glucose under anaerobic conditions leads to (a) a decrease in the rate of glucose consumption and (b) cessation of lactate accumulation. The latter phenomenon is known as the Pasteur effect. Explain why these changes occur in glucose and lactate metabolism. 

Subsequent reports described a syndrome of type B lactic acidosis in patients treated with zidovudine and other nucleoside reverse transcriptase inhibitors, including stavudine, lamivudine, and didanosine which has also been attributed to mitochondrial DNA toxicity [95-106]. There are five types of DNA polymerase in human cells that catalyze the synthesis of new complementary DNA from the original DNA template (HIV encodes a reverse transcriptase DNA polymerase which uses RNA as the template). The active triphosphate metabolites of zidovudine, didanosine, and stavudine inhibit DNA polymerase gamma in mitochondria, block the elongation of mitochondrial DNA, and deplete mitochondrial DNA [91-93,101,105-108]. The link between NRTl effects on mitochondrial DNA and lactic acidosis is not entirely clear but is most likely related to disturbances of oxidative phosphorylation and impaired pyruvate metabolism leading to lactate accumulation. 

The risk of lactate accumulation should be appreciated in patients with renal insufficiency, liver dysfunction and after acute illness with hypoxia, when therapy should be stopped. Although metformin is often bracketed with phenformin in the context of lactacidosis, different pharmacodynamics and adherence to prescribing guidelines render such a comparison unwarranted (Bailey and Nattrass, 1988). 

Lactate accumulation Stimulation Adenylate cyclase Inhibition... 

Under normal conditions, lactate is metabolized in the liver and the blood lactate level is between 1 and 2 mM. Lactate accumulation in body fluids can be due to increased production and/or decreased utilization. Blood lactate-to-pyruvate ratio below 25 suggests defects in a gluconeogenic enzyme (Chapter 15) or pyruvate dehydrogenase (discussed later). A common cause of lactic acidosis is tissue hypoxia caused by shock, cardiopulmonary arrest, and hypoperfusion. Inadequate blood flow leads to deprivation of oxygen and other nutrients to the tissue cells as well as to the removal of waste products. Oxygen deprivation leads to decreased ATP production and accumulation of NADH, which promotes conversion of pyruvate to lactate. 

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