The toxic action of oxygen on glucose and pyruvate oxidation in heart homogenates.

The experiments reported in this paper are concerned with the inhibitory action of oxygen at 1 atmosphere pressure on the carbohydrate metabolism of heart muscle studied in vitro. It has been observed by several investigators that oxygen at 1 atmosphere pressure may have a harmful effect on the metabolism of mammalian tissue in vitro or on individual enzyme systems (l-5). Dickens (6, 7) and Stadie and coworkers (8, 9) have studied systematically the effect of oxygen at elevated tension on tissue respiration and on the activity of various enzymes. The conclusions arrived at by the two groups of investigators were similar: Many enzymes, particularly those dependent upon sulfhydryl groups for activity, are more or less easily inactivated by oxygen pressures of 1 atmosphere or greater and many are completely resistant to the toxic action of oxygen. The enzymes inactivated by oxygen in vitro usually require 1 or more hours of exposure to 1 atmosphere of oxygen before inhibition becomes apparent. Even at oxygen pressures as high as 8 atmospheres, tissue respiration in vitro is only slowly inhibited. It has also been a general finding that enzymes in tissue extracts or homogenates are more readily inactivated than the same enzymes when present in the intact cells of tissue slices. For these and other reasons, it has been difficult to relate the effects of oxygen observed in vitro to the severe symptoms of oxygen poisoning produced within 15 to 30 minutes in animals exposed to 3 to 8 atmospheres of oxygen (5, 10, 11). The review by Dickens (5) contains an excellent critical evaluation of the work that has been carried out on the toxic action of oxygen on enzymes and tissue metabolism. From recent work on the mechanism of oxygen poisoning in the intact animal, it appears that there is a close similarity between the toxic effects of excess radiation and of oxygen at high pressure (12, 13). In the present work, the effect of 1 atmosphere of oxygen on the multienzyme systems involved in the oxidation of glucose and pyruvate has been studied. Rat heart homogenates fortified with KC1 and diphos-