Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules.

Kidney proximal tubules are resistant to hypoxic injury if glycine or L-alanine is present in their incubation medium. Protection does not depend on the concentration or turnover of ATP in cells. We have investigated structure-function relationships that govern this protective activity. Among more than 45 amino acids and analogs examined, only glycine, L-alanine, D-alanine, beta-alanine, and the neuronal glycine binding site agonist, 1-aminocyclopropane-1-carboxylic acid, were active. The protective effect could not be explained by amino acid metabolism. Ultrastructural features in protected cells were preserved to a degree which suggested that processes responsible for degradation during hypoxia were retarded. These results are consistent with stringent requirements of amino acid molecular structure for protection against hypoxia, and suggest the involvement of highly specific, acceptor-ligand effects on a process critical for maintaining cellular integrity.