The metabolism of lactic and pyruvic acids in normal and tumour tissue

THE formation and breakdown of lactic acid have been very extensively studied in muscle tissue and bacteria; in animal tissues other than muscle the metabolism of lactic and pyruvic acids has been investigated chiefly by feeding, injection and perfusion experiments on whole animals and organs.The introduction by Warburg of the surviving tissue slice technique with manometric measurements has given us a considerably more precise means for studying local intermediary metabolic processes, and lately the usefulness of such methods has been demonstrated by Krebs and Dickens and their collabo- rators and others.The apparatus recently developed by Dixon and Keilin [1933] has provided a means whereby the oxygen uptake, respiratory quotient and acid formation or disappearance can be measured simultaneously on the same sample of tissue in the presence of a bicarbonate-containing medium.The work described in this series should demonstrate the utility of this apparatus and, we hope, throw considerable light on the activity of the various tissues in metabolising lactic and pyruvic acids, including the intermediate stages in the breakdown of these substances.Combined with the manometric experiments, chemical estimations are carried out on the manometer contents to determine formation or disappearance of lactic acid, pyruvic acid and glycogen.In this paper we describe the details of our methods and the results obtained with kidney cortical tissue, chiefly of the rabbit.Though this tissue does not form or metabolise lactic acid to any great extent, it appears [Krebs, 1933] to be the chief seat of the oxidative deamination of amino-acids and would be expected therefore to have a high power for dealing with keto-acids.Later papers will deal with other tissues amenable to the method in the hope that light may be thrown on differences of behaviour in tissues such as tumour, wherein lactic acid is rapidly formed, brain and diaphragm which have the capacity for forming it anaerobically and liver wherein glycogen appears to be produced from lactic and pyruvic acids [see e.g.Meyerhof et al., 1926].The question of the metabolism of keto-acids other than pyruvic acid may be studied later.