Neutral Amino Acids and the Ion Gradient Hypothesis

Abstract

Current hypotheses about the mechanism of transduction of metabolic energy into osmotic work during the transport of amino acids in mammalian tissues centre about the question how sodium ions and potassium ions affect the process. The work of Christensen and his colleagues early indicated that, when mouse ascites tumour cells absorbed various neutral amino acids, the cellular content of Na+ increased and that of K+ decreased (reviewed by Christensen, 1970). The time scale and stoichiometry of the ionic changes followed a complex pattern in relation to the amino acid movements and it was not easy to interpret the results. Nevertheless Riggs, Walker and Christensen (1958) were later able to show that the amount of glycine accumulated by the mouse cells during one hour at 37°C was progressively lowered when cellular K+ ions were replaced by Na+ ions to an increasing extent. These and other observations led to the now familiar hypothesis, which has been applied to various mammalian tissues, that the spontaneous movements of Na+ ions or K+ ions across the cell membrane, down their respective cencentration gradients, might drive the amino acid into the tumour cells without the direct intervention of ATP. The concept is conveniently referred to as the ion gradient hypothesis. Though he had no evidence implicating protons in the system, Christensen (1960) envisaged the possibility that a concentration gradient of other ions such as H+ might also serve to propel the amino acid up its own concentration gradient.