Nitrogen recycling buffers against ammonia toxicity from skeletal muscle breakdown in hibernating arctic ground squirrels. 2020

Sarah A Rice, and Gabriella A M Ten Have, and Julie A Reisz, and Sarah Gehrke, and Davide Stefanoni, and Carla Frare, and Zeinab Barati, and Robert H Coker, and Angelo D'Alessandro, and Nicolaas E P Deutz, and Kelly L Drew
Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, USA.

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 15N 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.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D009210 Myofibrils The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES . Myofilaments,Myofibril,Myofilament
D009584 Nitrogen An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.
D011623 gamma-Glutamyl Hydrolase Catalyzes the hydrolysis of pteroylpolyglutamic acids in gamma linkage to pterolylmonoglutamic acid and free glutamic acid. EC 3.4.19.9. Conjugase,Folate Conjugase,Folyl Conjugate Synthetase,Pteroyl Polyglutamate Hydrolase,Carboxypeptidase G,Carboxypeptidase G1,Carboxypeptidase G2,Folacin Conjugase,Folate Hydrolyzing Enzyme,Folyl Poly-gamma-Glutamate Carboxypeptidase,Folyl Polyglutamate Cleavage Enzyme,Folylpolyglutamate Hydrolase,gamma Glutamyl Hydrolase
D006605 Hibernation The dormant state in which some warm-blooded animal species pass the winter. It is characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. Hibernation, Artificial,Induced Hibernation,Artificial Hibernation,Artificial Hibernations,Hibernation, Induced,Hibernations,Induced Hibernations
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D000641 Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001110 Arctic Regions The Arctic Ocean and the lands in it and adjacent to it. It includes Point Barrow, Alaska, most of the Franklin District in Canada, two thirds of Greenland, Svalbard, Franz Josef Land, Lapland, Novaya Zemlya, and Northern Siberia. (Webster's New Geographical Dictionary, 1988, p66)
D001143 Arousal Cortical vigilance or readiness of tone, presumed to be in response to sensory stimulation via the reticular activating system. Vigilance, Cortical,Arousals,Cortical Vigilance

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