Role of ornithine as a proline precursor in healing wounds

The successful healing of wounds requires the local synthesis of significant amounts of collagen. The amino acid pool that is the immediate precursor for collagen synthesis within wounds has not been specifically identified but is likely to include the free amino acids contained in the extracellular wound fluid. This fluid is here shown to be rich in proline and its metabolic precursors: ornithine, glutamate, and glutamine. While the metabolic origins for wound fluid glutamine and glutamate remain undetermined, ornithine is known to be synthesized locally through the catabolism of arginine by arginase. Experiments reported here tested the hypothesis that ornithine accumulating in the extracellular space of wounds serves as a precursor for proline contained in fibroblast secretory proteins. Results demonstrated that little ornithine is directly incorporated as protein-bound proline by wound-derived fibroblasts in culture and that the incorporation ornithine-derived proline into protein is markedly suppressed by preformed proline. In turn, the appearance of ornithine-derived free proline in the culture supernatants is quantitatively more important than its incorporation into protein and it is enhanced, rather than suppressed, by preformed proline. Therefore, ornithine may contribute to the synthesis of protein-bound proline in wounds by increasing the extracellular pool of free proline.