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Additive effects of glucagon and non-metabolizable analogue of leucine on glutamine catabolism in rat hepatocytes

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5018643

..beta..-2-Aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (BCH), at 10 mM, a known activator of glutamate dehydrogenase, doubled the rate of urea synthesis in hepatocytes from fed rats incubated with 10 mM glutamine (gln) and 2 mM ornithine. The stimulation of urea formation was accompanied by 1.4-fold activation of /sup 14/CO/sub 2/ release from (U-/sup 14/C)gln and 2.5-fold decline in intracellular gln content. There was no significant change in glutamate level while 2-oxoglutarate and malate increased by 1.3- and 2.4-fold, respectively. In hepatocytes from fasted rats BCH was similarly effective in stimulation of urea and /sup 14/CO/sub 2/ formation and it also doubled the rate of glucose synthesis. Effects of BCH on hepatocytes from fasted rats were associated with about 2-fold elevation of glutamate, aspartate and alanine levels. The effects of BCH and glucagon (a putative glutaminase activator) on urea, /sup 14/CO/sub 2/ and glucose formation were additive. The results suggest that BCH-induced activation of gln catabolism in hepatocytes is caused primarily by stimulation of glutaminase rather than glutamate dehydrogenase. It seems that the mechanisms of activation of glutaminase by BCH and glucagon are different.

Research Organization:
Univ. of Pennsylvania Medical School, Philadelphia
OSTI ID:
5018643
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English