Human neonates in intensive care units who are being fed by intravenous or enteral formulations receive no or very minimal glutamine at a time when they appear to need it most. Glutamine is an amino acid found in human milk and amniotic fluid in relatively high concentration when compared to infant formulas. Glutamine is a key fuel for the intestine and an essential precursor for nucleic acid biosynthesis in all cells. Because of this, we have initiated an investigation in our neonatal intensive care units to compare the outcome of very high risk, low birth weight neonate who are being fed therapeutic quantities of glutamine vs. standard glutamine. This clinical project (funded by non-NIH sources_ will determine whether these neonates benefit from therapeutic glutamine, but will leave numerous questions about basic glutamine metabolism in the rapidly maturing individual unresolved. We are thus proposing the following study, to be done in rats, which will complement the human clinical project. It will define glutamine metabolism during development from fetal life to adulthood and the factors which modulate glutamine metabolism. In this study we well determine the activities and quantities of intestinal glutaminase and glutamine synthetase along with their specific mRNAs during maturation. These will be determined concurrently in order to detect differences in cellular processing at different developmental stages. Immunohisto/cytochemical studies at both light and electron microscopic levels will provide us with previously undetermined cellular localization of these enzymes. In-situ- hybridization will localize the site of production of these enzymes. The effects of glucocorticoid administration on the activities of these enzymes, their mRNA, and transport properties through the intact small intestine, brush border and basolateral membrane, both antenatally and postnatally, will be determined. Relationships between the rapidly changing endogenous glucocorticoid milieu during maturation and alteration in small intestinal glutamine metabolism and transport will be established. It is anticipated that these rat studies in conjunction with human studies in our Neonatal Intensive Care Unit will provide and understanding of the mechanisms involved in small intestinal glutamine metabolism and protection at different developmental stages and provide indications for adding glutamine to infant formulas.
| DeMarco, V; Dyess, K; Strauss, D et al. (1999) Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells. J Nutr 129:57-62 |
| Weiss, M D; DeMarco, V; Strauss, D M et al. (1999) Glutamine synthetase: a key enzyme for intestinal epithelial differentiation? JPEN J Parenter Enteral Nutr 23:140-6 |
| DeMarco, V; McCain, M D; Strauss, D et al. (1997) Characterization of glutamine synthetase transcript, protein, and enzyme activity in the human placenta. Placenta 18:541-5 |
| Neu, J; Shenoy, V; Chakrabarti, R (1996) Glutamine nutrition and metabolism: where do we go from here ? FASEB J 10:829-37 |
| Shenoy, V; Roig, J C; Chakrabarti, R et al. (1996) Ontogeny of glutamine synthetase in rat small intestine. Pediatr Res 39:643-8 |
| Roig, J C; Shenoy, V B; Chakrabarti, R et al. (1995) Localization of rat small intestine glutamine synthetase using immunofluorescence and in situ hybridization. JPEN J Parenter Enteral Nutr 19:179-81 |
