Proline Metabolism in Severely Burned Patients: Effect of Modulated Parenteral Feeding

Proline is a non-essential amino acid. Its synthesis and catabolism is via the pathway of
ornithine and glutamate, the latter two amino acids serve as its immediate precursors as
well as metabolites. Ornithine is one of the intermediates for urea cycle, and glutamate is
metabolically connected to tricarboxylic acid (TCA) cycle, the major cycle for energy
production.

It is hypothesized that the significantly increased rates of net nitrogen loss and energy
"production", as the consequence of the accelerated activities of both the urea and TCA
cycles in burn injury "drain" both ornithine and glutamate, thus depleting tissues of the
availability of proline. Hence, the de novo synthesis of proline is likely to be affected by
the reduced availability of its major precursors: glutamate and ornithine.

This hypothesis is supported by 1) tissue and circulating glutamine content are reduced in
stressed conditions; 2) ornithine disposal via oxidation is significantly increased after
burn injury(2). Therefore, the availability of proline is likely to be limiting after burn
injury for the synthesis of proteins. On the other hand, proline requirement is
significantly increased in burn patients due to the high demand for tissue repair and wound
healing. As a result, providing an adequate proportion of its precursors, glutamine /
glutamate and / or as preformed proline, is of importance to maintain the appropriate supply
and balance of amino acids for protein and other synthetic functions after burn injury.

The overall purpose of the study is to evaluate the effect of depleting proline supply in
the nutritional support regimen on proline metabolism in the burn patients, this includes
the rate of proline oxidation after burn injury, the rate of proline de novo synthesis from
its immediate precursors glutamate and ornithine. The specific aims of the proposed study
are: 1) to determine the kinetic status of proline metabolism and whole body proline balance
under the following nutritional states: (a) "fasting; (b) regular total parenteral nutrition
(TPN); (c)TPN with isonitrogenous depletion of proline, glutamate and ornithine metabolism
under nutritional conditions studied in specific aim 1) above.

Inclusion Criteria:

Burn patients being treated at MGH Burn Unit with one or more of the following criteria:
1) >=5% TBSA; 2) inhalation injury; or 3) resting energy expenditure (REE) of >15% of the
predicted Basal Metabolic Rate using the Harris-Benedict equation.

Must be receiving total parenteral nutrition in the course of their treatment.

Exclusion Criteria:

Patients with thyroid disease. Patients who are not hemodynamically stable or show
unstable vital signs Patients at the stage of major organ failure, e.g. renal and/or liver
failure.