It has been shown that helium has the ability to affect variously the rates of certain metabolic reactions in vitro as compared to nitrogen. An attempt has been made to approximate the sites of action in mouse liver preparations.

The following results have been obtained by the substitution of a mixture of 80 per cent helium and 20 per cent oxygen for air: (a) An increase in the rate of oxygen consumption and carbon dioxide production to the same degree, the respiratory quotient remaining unchanged. (b) A decrease in the magnitude of cyanide inhibition. The effectiveness of helium increases with the degree of the cyanide inhibition. (c) No effect on the activity of slices which have been poisoned with fluoride when either lactate or pyruvate has been added as a substrate. (d) A change in the rate, and the slope of the curve of oxygen consumption in liver homogenates which are utilizing pyruvate as a substrate.

The use of helium relative to nitrogen under anaerobic conditions causes: (a) A depression of the glycolytic rates in both mouse liver slices and diaphragm. (b) An increase in the carbon dioxide evolution and lactic acid production of mouse liver homogenates oxidizing either glucose and hexose diphosphate, or hexose diphosphate alone.

In neither slices nor homogenates does the addition of fluoride and the use of pyruvate as the hydrogen acceptor alter the fundamental response of the preparations.

The following hypotheses have been advanced and discussed in order to explain the observed phenomena:

1. Helium does not alter the substrate utilized by the tissue.

2. The gas interferes in some way with the cyanide-cytochrome oxidase bond, but may not affect cytochrome oxidase in the absence of cyanide.

3. The citric acid cycle is not subject to the influence of helium in tissue slices, but is altered in an unexplained fashion in homogenates. It is postulated that a rearrangement of particulate surfaces may be the significant factor here.

4. The glycolytic cycle is the site of both an inhibitory and an acceleratory effect of helium. The locus of the inhibition lies above the aldolase reaction and that of the acceleration between the aldolase and enolase reactions.

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