Glutamine synthesis from glucose and ammonium chloride by guinea-pig kidney tubules

Abstract

1. At a physiological concentration (5 mM), glucose was found to be metabolized by isolated kidney cortex tubules prepared from fed guinea pigs. 2. The release of 14CO2 from [U-14C]glucose indicated that oxidation of the glucose carbon skeleton represented about 50% of the glucose removed; significant amounts of lactate and glutamine also accumulated. 3. Addition of 0.1-10 mM NH4Cl led to a dose-dependent stimulation of glucose metabolism which was accompanied by a large increase in lactate and glutamine accumulation and, to a lesser extent, in glucose oxidation. 4. Comparison of the release of 14CO2 from [1-14C]- and [6-14C]glucose indicates that, in both the absence and the presence of NH4Cl, the pentose phosphate shunt was only a minor pathway of glucose metabolism. 5. The central role of pyruvate carboxylase in the conversion of glucose carbon into glutamine carbon was demonstrated by using a bicarbonate-free medium and measuring the fixation of 14CO2 from [14C]bicarbonate, which was recovered mostly at C-1 of glutamine plus glutamate. 6. The NH4Cl-induced stimulation of glucose removal was secondary not only to increased glutamine synthesis, as shown by the effect of methionine sulphoximine, an inhibitor of glutamine synthetase, but also to the stimulation of phosphofructokinase activity by NH4Cl. 7. Renal arterio-venous difference measurements revealed that, in vivo, the guinea-pig kidney removed glucose from the circulating blood, which suggests that glucose carbon may contribute to the carbon skeleton of the glutamine released by this organ.

Insulin‐independent glucose transport regulates insulin sensitivity

“…In addition to its traditional role, muscle tissue has other functions, such as a role in immunology. The amino acid glutamine is synthesized from glucose in the skeletal muscle [8, 9]. Continuous maintenance of a sufficient glutamine concentration in the blood is necessary for the proper functioning of the immune system and survival [10].…”

Infusion of an acidified ethanolic—dextrose solution enhances urinary ammonium excretion and increases acid resilience in non—mechanically ventilated acidotic rabbits

“…Finally, the high glutamine synthetase activity, found in rabbit kidney nephrons ( Chauvin et al, 1997 ), has been shown to trap ammonia as glutamine, thus rendering it unavailable for release into both the urine and the systemic circulation via the renal vein. Furthermore, glutamine synthetase activity in herbivorous kidneys has been shown to be increased following the administration of ammonium chloride ( Michoudet et al, 1994 ).…”

Carbohydrate depletion has profound effects on the muscle amino acid and glucose metabolism during hyperinsulinaemia

“…Glucose contributes particularly for the production of alanine by providing its carbon skeleton[3]. There is also evidence suggesting that glucose may also provide carbon skeleton for glutamine[3–6]. This–together with the insulin‐stimulated uptake of some amino acids–leads to a net protein synthesis in the muscle during hyperinsulinaemia[7,8].…”

“…Because large amounts of proteins are synthesized and degraded daily[9], it is difficult to perceive the contribution of glucose‐derived amino acids to the amino acid pool during hyperinsulinaemia. However, there is a net release of alanine and glutamine from the muscle due to the conversion of glucose to alanine and possibly also to glutamine[4–6,10]. Alanine can be used for gluconeogenesis in the liver[11].…”