Effect of glutamine-supplemented parenteral nutrition on mortality in critically ill patients.

Glutamine is recognized as a critical amino acid involved in immunity, intestinal health, and nitrogen transport between organs. Prior to the pivotal study by Griffiths and colleagues in 1997, no clinical trials had demonstrated a positive effect from glutamine supplementation on improving long-term survival in critically ill intensive care unit patients receiving parenteral nutrition. Subsequent investigations have confirmed these findings, but further data are needed to determine the optimal dose and timing of glutamine as well as the form of glutamine (ie, free vs dipeptide) that produces the most significant improvement in outcome parameters.

Amino acids, then and now--a reflection on Sir Hans Krebs' contribution to nitrogen metabolism.

H. A. Krebs made an enormous contribution to our knowledge of amino acid metabolism, beginning with his studies on proteolysis in the early 1930s, progressing through his work on urea synthesis to an extensive series of papers on deamination and, then, to work on gluconeogenesis from amino acids. This paper addresses three of Krebs' early contributions-urea synthesis, glutamine metabolism, and D-amino acid oxidase-and relates them to our modern understanding of amino acid metabolism.

A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture: effect of nutrient concentration, dilution rate, and pH. Reprinted from Biotechnology and Bioengineering, Vol. 32, Pp 947-965 (1988).

Hybridomas are finding increased use for the production of a wide variety of monoclonal antibodies. Understanding the roles of physiological and environmental factors on the growth and metabolism of mammalian cells is a prerequisite for the development of rational scale-up procedures. An SP2/0-derived mouse hybridoma has been employed in the present work as a model system for hybridoma suspension culture. In preliminary shake flask studies to determine the effect of glucose and glutaminE, it was found that the specific growth rate, the glucose and glutamine metabolic quotients, and the cumulative specific antibody production rate were independent of glucose concentration over the range commonly employed in cell cultures. Only the specific rate of glutamine uptake was found to depend on glutamine concentration. The cells were grown in continuous culture at constant pH and oxygen concentration at a variety of dilution rates. Specific substrate consumption rates and product formation rates were determined from the steady state concentrations. The specific glucose uptake rate deviated from the maintenance energy model(1) at low specific growth rates, probably due to changes in the metabolic pathways of the cells. Antibody production was not growth-associated; and higher specific antibody production rates were obtained at lower specific growth rates. The effect of pH on the metabolic quotients was also determined. An optimum in viable cell concentration was obtained between pH 7.1 and 7.4. The viable cell number and viability decreased dramatically at pH 6.8. At pH 7.7 the viable cell concentration initially decreased, but then recovered to values typical of pH 7.1-7.4. Higher specific nutrient consumption rates were found at the extreme pH values; however, glucose consumption was inhibited at low pH. The pH history also influenced the behavior at a given pH. Higher antibody metabolic quotients were obtained at the extreme pH values. Together with the effect of specific growth rate, this suggests higher antibody production under environmental or nutritional stress.