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.

Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota

“…Moreover, elevated hepatic acetate levels suggest increased fatty acid catabolism, as acetate is an end product of fatty acid oxidation in liver peroxisomes 32, 33 . The glucogenic and ketogenic essential amino acids phenylalanine and tyrosine are important for energy generation and they are also precursors of thyroid hormone and catecholamines (e.g., dopamine, epinephrine, norepinephrine) that act on adipose tissue to modulate lipolysis and thermogenesis 23 . An upregulation of phenylalanine and tyrosine in the liver of tempol treated mice might indicate an alteration in energy production and lipid metabolism.…”

Comparison of Brain Transcriptome of the Greater Horseshoe Bats (Rhinolophus ferrumequinum) in Active and Torpid Episodes

“…The concentration of blood glucose is low during bat torpor [42]. The brain prefers to utilize ketones rather than glucose as the primary energy source during hibernation.…”

Homocysteine Homeostasis and Betaine-Homocysteine S-Methyltransferase Expression in the Brain of Hibernating Bats

“…The significant difference in selective pressure between hibernators and non-hibernators may be the result of environmental stressors, such as low temperature and food shortage [33]. This analysis supported the functional importance of BHMT during hibernation.…”