L(+) Lactic Acid and the Steady State of Cellular Red/Ox‐systems

Abstract

The role of L(+) lactic acid in the metabolism of individual cells and also in organized cell systems is defined by the concepts of "fermentation" and "oxygen debt." Both expressions, which are derived from the early days of physiological cell research, point already toward the close relationship of lactic acid to the oxydation systems of the cell, which will be the subject matter of the following.We owe the first systematic studies of the lactic/pyruvate Red/Ox-system to Huckabee,' who showed that the lactate/pyruvate ratio in the human blood remains extraordinarily constant, even when the total amount of lactate and pyruvate had risen over the normal value that could be obtained by pyruvate or bicarbonate infusion. Only under condition? under which the organism enters into an oxygen debt, as, for instance, during muscular work, Huckabee' found a rise of the lactate/pyruvate ratios too. This was, together with the difference of the lactate and pyruvate level, brought into a quantitative relationship to the oxygen debt and was termed "excess lactate." Huckabee assumed further that the lactate/pyruvate system, because of its ability to permeate through cell walls, would reflect the reduction state of ,the nicotinamidedinucleotide-system (NAD/NADH) in the cells of the body. Especially so since one could expect, because of the final position of the lactatedehydrogenase reaction in the Embden-Meyerhof system, a very close approximation of the steady state of lactate/pyruvate to the static equilibrium position with the NAD/NADH system. Holzer eta1.3 arrived a t the same conclusion for the analogous system acetaldehyde/ethanol in fermenting baker's yeast; also Czok,' from Buecher's Marburg group, related arteriovenous differences of lactate and pyruvate in the human brain to the NAD/ NADH ratio inside the brain cells. Undoubtedly, as Huckabee already has emphasized, it is not possible to count on a uniform state of reduction of the NAD/NADH system in all the different tissues and cells of the body. Therefore, the postulated relationship between the lactate/pyruvate ratio in the blood and the state of reduction of the NAD/NADH system inside the cells of the body requires a further differentiated analysis.Asa matter of fact the measurement of lactate and pyruvate in various tissues of the rat under conditions that permit an adequate fixation of the in vim state of the metabolites shows differences both in their total amounts and 974

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