ENTERAL GLUTAMINE SPARES ENDOGENOUS GLUTAMINE IN CHRONIC ACIDOSIS

Metabolic acidosis associated with the catabolic state mobilizes muscl e nitrogen and releases it into blood as glutamine (GLN) targeted for renal consumption and base generation. Because GLN removed by the kidn eys during acidosis is a major drain on the GLN available to other sit es, subsequent deprivation may lead to impaired organ function. Conver sely, GLN supplementation may spare endogenous supplies and restore or gan function. To test this, Sprague-Dawley rats weighing between 250 a nd 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 fo r GLN (ED). Acid loading was effected by adding hydrochloric acid to t he liquid diet (110 mmol/L). Animals were studied in metabolic cages f or five consecutive 24-hour urine collection periods and then anesthet ized for short-term studies of interorgan fluxes and tissue GLN conten t. Acidosis effected an increase in ammonium nitrogen excretion (fivef old) and a reciprocal decrease (24%) in urea nitrogen excretion. Enter al GLN had no effect on the acidosis-effected ammonium (2170 +/- 71 vs 2059 +/- 361 mumol/100 g, ED vs GLN-ED, respectively) or urea excreti on (5522 +/- 95 vs 5915 +/- 984 mumol/100 g, ED vs GLN-ED, respectivel y). 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 +/- 48 9 and 4742 +/- 333 nmol/g, respectively, each p < .05). GLN released b y 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 G LN release decreased in the GLN-ED group compared with the ED group (5 07 +/-104 vs 162 +/- 148, p < .05). In contrast, gut GLN uptake was ma rkedly 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 creatin ine excretion increased with GLN-ED, whereas 3-methylhistidine excreti on 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 spari ng proteolysis during chronic metabolic acidosis apparently dependent upon enhanced interorgan flux of the GLN precursor glutamate.