Acute effects of glucagon on citrulline biosynthesis

Abstract

Mitochondria isolated from livers of rats fed on different diets showed altered capacity to synthesize citrulline. Glucagon, 15 min after injection, increases citrulline biosynthesis, except after the high-protein diet. A significant correlation between citrulline biosynthesis and N-acetylglutamate content with and without glucagon treatment was shown when rats were fed on a standard or a carbohydrate diet. Different diets modified carbamoyl phosphate synthetase I (EC 6.3.4.16) and N-acetylglutamate synthase (acetyl-CoA:L-glutamate N-acetyltransferase, EC 2.3.1.1) activities. Glucagon did not modify these activities.

Effects of Corticosteroids and Pancreatic Hormones on Carbamyl Phosphate Synthetase-I and Ornithine Transcarbamylase Activities in Fetal Rat Liver

“…At this stage, only dibutyryl-cAMP increases OTC activity, and this stimulatory effect is not abolished by supplementing hydrocorti sone acetate. These results are consistent with previous reports [11,12,17,19,22], The stimulatory effect of glucagon on mito chondrial citrullinogenesis is probably asso ciated with an increase in CPS-I activity since OTC activity is not rate-limiting. De spite high fetal insulinemia, glucagon may act on OTC activity by rapidly altering the insulin/glucagon ratio.…”

“…It is known from previous studies [13,15,21] that their activities need the presence of adrenals in the neonate and adult rat. Moreover the stimulatory effect of glucagon on their activities is a well-estab lished fact in adult rats 'in vivo'[l4, 16,23] and in primary monolayer cultures of adult hepatocytes 'in vitro' [9], More recently, it has been reported that glucagon stimulates citrullinogenesis in isolated mitochondria by increasing mitochondrial N-acetylglutamate level, the activator of CPS-I activity [11,17].…”

On the nature of the stimulation by glucagon on citrulline synthesis in rat‐liver mitochondria

“…Since >70% of intracellular N-acetylglutamate is intramitochondrial [2,8,9], we conclude that the N-acetylglutamate content of the mitochondria in the intact hepatocyte is also increased by glucagon. The capacity of liver mitochondria to synthesize citrulline is dependent on the magnitude of the intramitochondrial concentration of N-acetylglutamate [2,6,9,10]. Thus, the stimulation of citrulline synthesis by glucagon is due to a direct activation of carbamoyl-phosphate synthetase.…”

“…[2]). Citrulline synthesis with glutamate as the respiratory substrate was higher than with succinate because of synthesis of N-acetylglutamate, the activator of carbamoyl-phosphate synthetase, during incubation [5,6]. In 6 out of the 10 preparations in each series, N-acetylglutamate was also (6) 184+7 (6) n.s.…”

Is N-acetylglutamate a short-term regulator of urea synthesis?

“…N-Acetylglutamate, the obligatory cofactor of carbamoyl phosphate synthetase (EC 6.3.4.16), is considered an important short-term regulator of urea synthesis (see Meijer & Hensgens, 1982;Rabier et al, 1982). It has been suggested that its rate of synthesis is regulated by the supply of mitochondrial glutamate (Tatibana & Shigesada, 1976;Stewart & Walser, 1980;Zollner, 1981).…”