Oligopeptides as sources of indispensable amino acids for mammalian cells in culture

Summary

The ability of peptides containing lysine to satisfy the lysine requirement of mammalian cells in a medium otherwise free of this indispensable amino acid was investigated. In contrast to bacteria, which are unable to utilize pentalysine and higher homologs, mammalian cells are able to grow in the presence of di- to decalysine. For each oligopeptide, the response was proportional to concentration within a limited range. The duration of the lag and logarithmic growth phases was directly proportional to peptide size, and the growth rate decreased with peptide size. Utilization of decalysine was not accompanied by the accumulation of smaller oligomers in the medium or in the trichloroacetic acid soluble fraction of a cell lysate. However, enzymes capable of hydrolyzing decalysine were clearly demonstrable inside the cells and in the spent culture medium. It is concluded that the rate of uptake is inversely proportional to peptide size and is growth rate-limiting, and that free lysine produced by intracellular peptidases is used as quickly as it is formed. Although the serum proteins used to supplement the growth medium contained more lysine in peptide linkage than is needed by the cells, this lysine is not available to the cells in significant amount.