Plasma free amino acids in hibernation and arousal

Klain, George J.; Whitten, Bertwell K.

doi:10.1016/0010-406x(68)90261-2

Cited by 27 publications

(8 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aromatic amino acids tryptophan, tyrosine, and phenylalanine were low in EN and LT squirrels and increased upon arousal to levels similar to SUM. Tyrosine and phenylalanine increase in plasma upon arousal in hibernating ground squirrels (28). In our NMR-based liver metabolomic study (42) levels of aromatic amino acids were similar in EN, LT, and SUM squirrels (IBA was not examined), which differs somewhat from our results.…”

Section: Discussioncontrasting

confidence: 91%

Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver

Nelson

Otis

Martin

et al. 2009

Physiological Genomics

View full text Add to dashboard Cite

A hallmark of hibernation in mammals is metabolic flexibility, which is typified by reversible bouts of metabolic depression (torpor) and the seasonal shift from predominantly carbohydrate to lipid metabolism from summer to winter. To provide new insight into the control and consequences of hibernation, we used LC/MS-based metabolomics to measure differences in small molecules in ground squirrel liver in five activity states: summer, entering torpor, late torpor, arousing from torpor, and interbout arousal. There were significant alterations both seasonally and within torpor-arousal cycles in enzyme cofactor metabolism, amino acid catabolism, and purine and pyrimidine metabolism, with observed metabolites reduced during torpor and increased upon arousal. Multiple lipids also changed, including 1-oleoyllysophosphatidylcholine, cholesterol sulfate, and sphingosine, which tended to be lowest during torpor, and hexadecanedioic acid, which accumulated during a torpor bout. The results reveal the dramatic alterations that occur in several classes of metabolites, highlighting the value of metabolomic analyses in deciphering the hibernation phenotype.

show abstract

Section: Discussioncontrasting

confidence: 91%

Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver

Nelson

Otis

Martin

et al. 2009

Physiological Genomics

View full text Add to dashboard Cite

show abstract

“…3 and Supplemental Fig. S2), the unmodified forms demonstrate highly variable levels and lack a consistent pattern, results that have been reported previously based on a targeted approach (24). Discovery of the coordinated changes in clusters of modified amino acids may have been particularly enabled in this study because the unique combination of the broad screening strategy with the multiple sampling points allowed measurement and identification of unanticipated modified forms that accumulated at the low T b of torpor.…”

Section: Discussionsupporting

confidence: 66%

“…Previous work to measure metabolite changes in hibernators documents a number of alterations in liver (2,32,36), brain (21,40), brown adipose tissue (13), bile (4), and blood (1,9,24,31) that begin to assess the metabolites cycling in association with hibernation. These data suggest a two-switch model for the circannual rhythm of hibernation whereby the torporarousal cycle is temporally segregated from the summer-winter cycle such that torpor-arousal occurs only in winter (36).…”

mentioning

confidence: 99%

Metabolic cycles in a circannual hibernator

Epperson¹,

Karimpour-Fard

Hunter

et al. 2011

Physiological Genomics

View full text Add to dashboard Cite

nation as manifested in ground squirrels is arguably the most plastic and extreme of physiological phenotypes in mammals. Homeostasis is challenged by prolonged fasting accompanied by heterothermy, yet must be facilitated for survival. We performed LC and GC-MS metabolomic profiling of plasma samples taken reproducibly during seven natural stages of the hibernator's year, three in summer and four in winter (each n Ն 5), employing a nontargeted approach to define the metabolite shifts associated with the phenotype. We quantified 231 named metabolites; 106 of these altered significantly, demarcating a cycle within a cycle where torpor-arousal cycles recur during the winter portion of the seasonal cycle. A number of robust hibernation biomarkers that alter with season and winter stage are identified, including specific free fatty acids, antioxidants, and previously unpublished modified amino acids that are likely to be associated with the fasting state. The major pattern in metabolite levels is one of either depletion or accrual during torpor, followed by reversal to an apparent homeostatic level by interbout arousal. This finding provides new data that strongly support the predictions of a long-standing hypothesis that periodic arousals are necessary to restore metabolic homeostasis. Ictidomys tridecemlineatus; Spermophilus; ␥-glutamyl; biliverdin; NacetylA YEAR IN THE LIFE OF A HIBERNATOR begins with reproduction in spring, followed by growth in summer, and then massive storage of fat as fall approaches. Hibernation, characterized by months of fasting and dramatic oscillations between states of cold and warm body temperature (T b ), ensues only after adequate fat stores are deposited (7). Most of the fall and winter months are spent in a state of deep torpor in which metabolic, heart, and respiratory rates are reduced to Ͻ5% of their summer equivalents, and body temperature declines to as low as 0°C, or even below (5). However, all hibernating mammals spontaneously reverse torpor at regular intervals by elevating metabolic rate and employing strictly endogenous mechanisms of heat production including shivering and nonshivering thermogenesis. In the thirteen-lined ground squirrel, Ictidomys tridecemlineatus, elevated metabolic rate and T b (ϳ37°C) are maintained in each interbout arousal for ϳ10 -12 h before dropping again to initiate the next ϳ2 wk bout of torpor. Thus, the circannual hibernation rhythm can be viewed as a cycle between summer homeothermy and winter heterothermy, the latter of which is itself a cycle between torpor and arousal (see Fig. 1). These dramatic physiological shifts of hibernation have been postulated to result from intrinsic metabolic cycles (41) that may be revealed by metabolic profiling (42).Previous work to measure metabolite changes in hibernators documents a number of alterations in liver (2, 32, 36), brain (21, 40), brown adipose tissue (13), bile (4), and blood (1, 9, 24, 31) that begin to assess the metabolites cycling in association with hibernation. These data suggest a two-s...

show abstract

“…Further support for this notion is the result of a recent study showing that the expressions of HPD and FAH mRNA are much higher in the heart of golden-mantled ground squirrels ( Spermophilus lateralis ) during late torpor [57]. Furthermore, increased levels of plasma phenylalanine and tyrosine are found in hibernating ground squirrels upon arousal [58]. It has also been found that the levels of aromatic amino acids (tyrosine, phenylalanine, and tryptophan) vary significantly in the liver of 13-lined ground squirrels ( Spermophilus tridecemlineatus ) in different stages of hibernation [14].…”

Section: Discussionmentioning

confidence: 91%

Adaptation of Phenylalanine and Tyrosine Catabolic Pathway to Hibernation in Bats

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

Plasma free amino acids in hibernation and arousal

Cited by 27 publications

References 4 publications

Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver

Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver

Metabolic cycles in a circannual hibernator

Adaptation of Phenylalanine and Tyrosine Catabolic Pathway to Hibernation in Bats

Contact Info

Product

Resources

About