On the stimulation of gluconeogenesis by L-lysine in isolated rat kidney cortex tubules.

Abstract

1. L-Lysins (2 mM) stimulates (30-50%) gluconeogenesis in isolated kidney cortex tubules from 24-h-starved rats in the presence of lactate and Krebs cycle intermediates, but not pyruvate and glutamate. The stimulation of renal gluconeogenesis by L-lysine is a short-term effect. The effect is of catalytic nature, but not due to sparing of substrate. L-lysine caused a decrease of lactate/pyruvate ratio. 2. Apart from L-lysine, 1-10 mM NH-4Cl (16-40%) and 2 mM aspartate (66%) were capable to stimulate gluconeogenesis from lactate. Other amino acids tested did not stimulate renal gluconeogenesis, except L-alanine. The stimulation of gluconeogenesis by lysine was not additive to the stimulation by NH-4Cl. Likewise, there was no stimulation of gluconeogenesis from lactate by L-lysine in the presence of glutamate or arnithine. Levels of ammonia, glutamate and aspartate were elevated in the presence of L-lysine, NH-4Cl or glutamate about two-fold, were capable to stimulate gluconeogenesis. 3. The stimulation of gluconeogenesis by L-lysine from malate, succinate and oxoglutarate was abolished in the presence of amino oxy-acetate (0.05 mM), whereas controls were not significantly affected. 4. After 1 h of incubation about 5% of added [U-14C] lysine was recovered as 14-CO-2. The extra ammonia formed in the presence of L-lysine would also correspond with about 5-10% of added lysine being metabolized. 5. 14-CO-2 formation from [1-14C] butyrate and [1-14C] palmitate was inhibited by 20-30% in the presence of 2 mM L-lysine. 6. O-2 uptake and cellular levels of K+ were not significantly affected by L-lysine. 14-CO-2 fixation from pyruvate and 14-CO-2 formation from [1-14C]-pyruvate by isolated, intact rat liver mitochondria remained unchanged by L-lysine. Likewise no direct effect of L-lysine on enzyme activities could be detected. 7. The data seem compatible with the assumption that stimulation of gluconeogenesis in isolated kidney cortex tubules by L-lysine is due to a stimulation of the malate-aspartate shuttle as a consequence of an increased provision of glutamate and aspartate.