Effect of 6-methylpurine on phosphohexose isomerase and lactic dehydrogenase activities of plasma, erythrocytes, liver, and skeletal muscle.

Although it has been stated that plasma or serum enzymes are derived from the destruction of cellular elements in the blood or tissues (8), indirect evidence has recently been accumulating that enzymes may pass outward from the cell into the extracellular fluid and thence into the circulation in ways other than those involving necrosis or destruction of the cell (2, 3, 5, 8). It has long been known and is generally well appreciated that elevations in serum alkaline phosphatase, acid phosphatase, amylase, and lipase may reflect certain nondestructive cellular and tissue processes in specific organs (4). A study of the effects of a variety of toxic agents on plasma phosphohexose isomerase activity indi cated that, although extensive necrosis might in some instances account for rises in this enzyme activity, it was not the only mechanism by which elevations could be induced (11). Of the various substances used (11), 6-methylpurine was of particular interest. The minimum lethal dose in dogs receiving ten consecutive daily injections was only 0.35 mg/kg/day, much lower than that for other purines (10). Administered in this dose to those species, 6-methylpurine caused a greatly protracted intoxication characterized by anorexia, progressive weight loss, and, of par ticular interest, sustained elevations in plasma phosphohexose isomerase activity. In the midst of these striking changes, renal and hepatic func tion remained essentially normal, and microscopic study failed to demonstrate consistent lesions of sufficient magnitude to account for the enzymatic alterations in the plasma.