Open AccessNitrogen recycling buffers against ammonia toxicity from skeletal muscle breakdown in hibernating arctic ground squirrels
Author(s) -
Sarah Rice,
Gabriëlla A. M. Ten Have,
Julie A. Reisz,
Sarah Gehrke,
Davide Stefai,
Carla Frare,
Zeinab Barati,
Robert H. Coker,
Angelo D’Alessandro,
N.E.P. Deutz,
Kelly L. Drew
Publication year - 2020
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-020-00312-4
Subject(s) - hibernation (computing) , amino acid , torpor , biology , biochemistry , metabolism , chemistry , ecology , state (computer science) , algorithm , computer science , thermoregulation
Hibernation is a state of extraordinary metabolic plasticity. The pathways of amino acid metabolism as they relate to nitrogen homeostasis in hibernating mammals in vivo are unknown. Here we show, using pulse isotopic tracing, evidence of increased myofibrillar (skeletal muscle) protein breakdown and suppressed whole-body production of metabolites in vivo throughout deep torpor. As whole-body production of metabolites is suppressed, amino acids with nitrogenous side chains accumulate during torpor, while urea cycle intermediates do not. Using 15 N stable isotope methodology in arctic ground squirrels (Urocitellus parryii), we provide evidence that free nitrogen is buffered and recycled into essential amino acids, non-essential amino acids and the gamma-glutamyl system during the inter-bout arousal period of hibernation. In the absence of nutrient intake or physical activity, our data illustrate the orchestration of metabolic pathways that sustain the provision of essential and non-essential amino acids and prevent ammonia toxicity during hibernation.