Characteristic Metabolism of Free Amino Acids in Cetacean Plasma: Cluster Analysis and Comparison with Mice

From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms) since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaption used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future

Hierarchical cluster analysis reveals different plasma aminogram patterns in cetaceans and mice.

<p>Dendrograms obtained from a hierarchical cluster analysis of the plasma aminograms are shown. Each amino acid concentration was normalized before the analysis, and the red and green squares represent high and low relative concentrations, respectively. Ward's linkage method was performed on the Euclidean distances obtained from the standardized aminogram. Briefly, this method seeks to choose successive clustering steps so as to minimize the increase in the error sum of squares found at each level. Bottlenose dolphins (n = 51), pacific white-sided dolphins (n = 16), Risso's dolphins (n = 19), false-killer whales (n = 4), C57BL/6J mice (n = 8) and ICR mice (n = 5) were used for this analysis. Orn, ornithine; Arg, Arginine; Cit, Citrulline, Thr, threonine; Lys, lysine; Ser, serine; Asp, Aspartate; Glu, Glutamate; Tau, Taurine; Gln, Glutamine; Gly, Glycine; Val, Valine; Ile, Isoleucine; Leu, Leucine; Asn, Asparagine; Cys, Cystine; Ala, Alanine; Pro, Proline; Met, Methionine; Tyr, Tyrosine; Trp, Tryptophan; Phe, Phenylalanine; His, Histidine; Cysthi, Cystathionine; 3-MH. 3-methylhistidine; Car, Carnosine.</p

Urine concentrations (mean ± SEM µmol/mg creatinine) of amino acids in bottlenose dolphins and mice.

<p>†Levels of carnosine were described as mean ± SEM × 10⁻² µmol/mg creatinine.</p><p>‡Carnosine was only detected in four samples of mouse urine.</p><p>*Significantly different between the bottlenose dolphins and mice (<i>P</i><0.001, LME-associated ANOVA).</p

Plasma levels of 3-MH and carnosine are higher in cetaceans.

<p>The plasma levels of 3-MH (A) and carnosine (B) are shown. Individual data points are shown as open circles, and bars indicate the average values. The different letters indicate significant differences (<i>P</i><0.05) among groups as determined by Tukey's test. ND  =  not detected. Bottlenose dolphins (n = 51), pacific white-sided dolphins (n = 16), Risso's dolphins (n = 19), false-killer whales (n = 4), C57BL/6J mice (n = 8) and ICR mice (n = 5) were used for this analysis.</p