The isoenzyme pattern of LDH does not play a physiological role; except perhaps during fast transitions in energy metabolism

A paper describing increased brain lactate concentration with age recently caught our attension The proposed explanation for the increased brain lactate with age was a shift in the brain lactate dehydrogenase (LDH) isoenzyme pattern, which also occurred with age. While the observations are highly interesting, we found the explanation unlikely under steady state conditions, since LDH is regarded a near-equilibrium reaction and since the equilibrium constant of all the LDH isoenzymes, of course, are the same We therefore decided to evaluate the question further, including a brief historical review, since a quick examination of common textbooks of biochemistry on the LDH isoenzyme question suggests that it is in fact common place to confer significant physiological importance to the different kinetic properties of the isoforms of LDH Historical: The concept of isoenzymes evolved in the late 1950's and early 1960's. In case of LDH it became clear that five isoenzymes numbered 1-5 could be distinguished according to electrophoretic mobility The various isoenzymes appeared to be tetramers of two different subunits, M and H. Isoenzyme 5 is composed of M-subunits only and is the predominant form in skeletal muscle and isoenzyme 1 is composed of H-subunits only and is found primarily in heart tissue. Isoenzyme 2-4 contains both subunits. Later studies showed that two proteins M and H are the products of the genes Ldh-A and Ldh-B, respectively, and the LDH enzyme presents with the following five isoenzymes: M 4 , MH 3 , M 2 H 2 , M 3 H and H 4 .