Future directions in clinical nutritional support in relation to wound healing

Current clinical research has focused on the role of ornithine and ornithine a-ketoglutarate on wound healing. Dietary ornithine supplementation increased wound breaking strength and collagen deposition in mice.43 Results from two randomized control trials demonstrated that ornithine a-ketoglutarate, a salt formed of two molecules of ornithine and one molecule of a-ketoglutarate, increased wound healing in burn patients.44 45 Further research is needed to reinforce these findings.

With regard to the specific nutrient requirement in burn injury, one amino acid of special interest is proline. Posttranslational modification of proline on collagen molecule is important to collagen formation and wound healing. The interstitial proline content has been found to be related to wound healing.46 Metabolically, proline is a nutritionally dispensable amino acid. Its formation and disposal are closely related to the metabolism of ornithine and glutamate (Figure 4.2). Ornithine is one of the components of the urea cycle, and glutamate availability is closely related to the metabolism of a-glutarate, an intermediate of the tricarboxylic acid (TCA) cycle (Figure 4.3). In patients with thermal injuries, hypermetabolism and increased nitrogen loss indicate an accelerated TCA cycle and accelerated urea cycle activities, which "drains" both ornithine and glutamate. Because proline occupies one corner of the metabolic "triangle" interrelating these three amino acids, the de novo synthesis of tissue proline is likely to be compromised in the burn condition. This notion is supported by three facts:

1. Stable isotope tracer studies by Jaksic et al. revealed a negative proline balance in patients with burns, suggesting a status of proline depletion.47

Proline

NADP+

NADP+

Proline

Dehydrogense

NADPH+H+

FADH+H+

FADH+H+

Proline

Dehydrogense

NADPH+H+

  • fad+ Pyrroline-5-carboxylate
  • Spontaneous)

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