Glycine transport in normal and non-ketotic hyperglycinemic human diploid fibroblasts

Uptake, inhibition and kinetic studies in control and non-ketotic hyperglycinemic human fibroblasts show that glycine transport is mediated by the three neutral amino acid carriers A, ASC, and L as described for ascites tumor cells by Oxender & Christensen [5]. NKH fibroblasts lines transported glycine at a reduced rate, and the final intracellular concentration of glycine was less than that of the controls. In both control and NKH lines, transport activity required metabolic energy, SH groups, Na + and K + ions. Kinetic data indicated that both control and non-ketotic hyperglycinemic lines had a similar K M but that the V max in the NKH cells was always lower suggesting that movement of the carrier and/or the dissociation of the carrier and glycine was depressed in the mutant lines. These data suggest that patients with non-ketotic hyperglycinemia have a defect in glycine transport instead of or in addition to a defective glycine cleavage reaction.