title: Adaptation of phenylalanine and tyrosine catabolic pathway to hibernation in bats.
abstract: Some mammals hibernate in response to harsh environments. Although hibernating mammals may metabolize proteins, the nitrogen metabolic pathways commonly activated during hibernation are not fully characterized. In contrast to the hypothesis of amino acid preservation, we found evidence of amino acid metabolism as three of five key enzymes, including phenylalanine hydroxylase (PAH), homogentisate 1,2-dioxygenase (HGD), fumarylacetoacetase (FAH), involved in phenylalanine and tyrosine catabolism were co-upregulated during hibernation in two distantly related species of bats, Myotis ricketti and Rhinolophus ferrumequinum. In addition, the levels of phenylalanine in the livers of these bats were significantly decreased during hibernation. Because phenylalanine and tyrosine are both glucogenic and ketogenic, these results indicate the role of this catabolic pathway in energy supply. Since any deficiency in the catabolism of these two amino acids can cause accumulations of toxic metabolites, these results also suggest the detoxification role of these enzymes during hibernation. A higher selective constraint on PAH, HPD, and HGD in hibernators than in non-hibernators was observed, and hibernators had more conserved amino acid residues in each of these enzymes than non-hibernators. These conserved amino acid residues are mostly located in positions critical for the structure and activity of the enzymes. Taken together, results of this work provide novel insights in nitrogen metabolism and removal of harmful metabolites during bat hibernation.
authors.affiliation: Laboratory of Molecular Ecology and Evolution, Institute for Advanced Studies in Multidisciplinary Science and Technology, East China Normal University, Shanghai, China.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Pan
authors.forename: Yijian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Cui
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: McAllan
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Liao
authors.forename: Shuyi
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000090:Acetoacetates / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D015153:Blotting, Western; D002685:Chiroptera / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D006605:Hibernation / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008958:Models, Molecular; D010649:Phenylalanine / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D012641:Selection, Genetic; D020539:Sequence Analysis, Protein; D014157:Transcription Factors / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000090:Acetoacetates; D020543:Proteome; D014157:Transcription Factors; D014443:Tyrosine; D010649:Phenylalanine; C016635:acetoacetic acid