Effects of urea, trimethylamine oxide, and osmolality on respiration and citrulline synthesis by isolated hepatic mitochondria from Squalus acanthias.

The effects of osmolality and of urea and trimethylamine oxide on citrulline synthesis and respiration by isolated hepatic mitochondria from Squalus acanthias (spiny dogfish) were determined. Optimal rates of citrulline synthesis and of respiration, as well as maximal respiratory control ratios, were obtained when the osmolality was about 300 mOsm when physiological concentrations of urea and trimethylamine oxide were present, analogous to mammalian mitochondria. Urea and trimethylamine oxide do not act as osmolytes and do not significantly affect these rates. When glutamate is not saturating, increasing concentrations of urea over the range of concentrations of physiological significance (e.g. 0.1-0.5 M) significantly inhibit citrulline synthesis, but not respiration. This response to urea concentration may reflect a specific homeostatic mechanism for maintaining physiological concentrations of urea.