Studies of glycine metabolism and transport in fibroblasts from patients with nonketotic hyperglycinemia

Abstract

Glycine transport in both normal and nonketotic hyperglycinemia fibroblasts was shown to occur by a sodium-dependent system. No significant difference could be detected in either the Km’s (1.4 to 2.0 mM) or the Vmax’s (6.2 to 16 nmole per mg protein per min) of the three control and three patient cell lines. Valine was a weak competitive inhibitor of glycine uptake. Ki’s from both groups fell into the 5.6 to 5.8 mM range. Plasma levels of valine of one patient reached a maximum of 0.6 mM following a valine load. Glycine cleavage activity could not be detected in either control or nonketotic hyperglycinemia fibroblast lines. Serine utilization was the same in both nonketotic hyperglycinemia and control lines. Speculation: The fibroblast lines of nonketotic hyperglycinemia patients used in our study indicate that a glycine transport defect is not the cause of the elevated cerebrospinal fluid glycine levels observed in nonketotic hyperglycinemia. The clinical valine effect is unlikely to be related to the inhibition of glycine transport by valine. © 1980 International Pediatric Research Foundation, Inc.