ENTERAL GLUTAMINE SPARES ENDOGENOUS GLUTAMINE IN CHRONIC ACIDOSIS

Metabolic acidosis associated with the catabolic state mobilizes muscle nitrogen and releases it into blood as glutamine (GLN) targeted for renal consumption and base generation. Because GLN removed by the kidneys during acidosis is a major drain on the GLN available to other sites, subsequent deprivation may lead to impaired organ function. Conversely, GLN supplementation may spare endogenous supplies and restore organ function. To test this, Sprague-Dawley rats weighing between 250 and 350 g were pair-fed elemental diets supplemented with GLN 4.9 g/L (GLN-ED) or an equivalent mixture of neutral amino acids substituted for GLN (ED). Acid loading was effected by adding hydrochloric acid to the liquid diet (110 mmol/L). Animals were studied in metabolic cages for five consecutive 24-hour urine collection periods and then anesthetized for short-term studies of interorgan fluxes and tissue GLN content. Acidosis effected an increase in ammonium nitrogen excretion (fivefold) and a reciprocal decrease (24%) in urea nitrogen excretion. Enteral GLN had no effect on the acidosis-effected ammonium (2170 +/- 71 vs 2059 +/- 361 mumol/100 g, ED vs GLN-ED, respectively) or urea excretion (5522 +/- 95 vs 5915 +/- 984 mumol/100 g, ED vs GLN-ED, respectively). Although arterial blood GLN was not increased in the GLN-ED group (531 +/- 58 vs 438 +/- 51 nmol/mL, p = .10), both liver and muscle GLN were elevated (11,650 +/- 1137 nmol/g vs 7063 +/- 578 and 5503 +/- 489 and 4742 +/- 333 nmol/g, respectively, each p < .05). GLN released by the hindquarter and liver and removed by the gut was monitored while the rats were under anesthesia by using simultaneously measured blood flow and arteriovenous blood concentration differences. Hindquarter GLN release decreased in the GLN-ED group compared with the ED group (507 +/-104 vs 162 +/- 148, p < .05). In contrast, gut GLN uptake was markedly increased in the GLN-ED group (477 +/- 153 to 931 +/- 228 mmol/min per 100 g, p < .05), whereas hepatic release increased (134 +/- 74 to 430 +/- 132 nmol/min per 100 g, p < .05). Although splanchnic bed GLN balance registers net uptake, urea excretion was not enhanced with GLN-ED; rather a large hepatic glutamate efflux appeared (343 +/- 150 to 827 +/- 240 mmol/min per 100 g, p < .05). Twenty-four-hour creatinine excretion increased with GLN-ED, whereas 3-methylhistidine excretion decreased (2.46 +/-018 vs 1.86 +/- 0.10 mumol/100 g for GLN-ED and ED, respectively, p < .05). These findings are consonant with enteral GLN supplementation effecting a reduced GLN flow from muscle and sparing proteolysis during chronic metabolic acidosis apparently dependent upon enhanced interorgan flux of the GLN precursor glutamate.