Trimethylamine oxide and urea synthesis in rainbow smelt and some other northern fishes.

Trimethylamine oxide (TMAO) and urea levels in the blood of rainbow smelt, Osmerus mordax, were previously shown to increase dramatically in winter, but the means by which these osmolytes are acquired has remained unclear. In this study, I show that the smelt can synthesize TMAO via liver trimethylamine oxidase activity and thus are not completely dependent on a dietary source of TMAO. Cold-acclimatized Pacific herring, Clupea harengus, were also found to have high levels of TMAO in the blood, while individuals from a temperate-water population of herring did not. Herring also had liver TMA oxidase activity, which appeared to be due to a flavin-containing monooxygenase. In both species, TMA oxidase activity did not appear to be strongly affected by temperature. TMAO data were obtained for three other northern species (Macrozoarces americanus, Eleginus gracilis, and Platichthys stellatus), and these results, together with previously reported data, suggest that TMA oxidase activity is a necessary condition for high levels of TMAO in the blood. In the smelt, urea appears to be synthesized via uricolysis and also through the action of arginase on dietary arginine, while the ornithine urea cycle appears to be nonfunctional. There was no relation among several species of northern fishes between levels of urea in the blood and levels of uricase or arginase activity. Together, these results provide further evidence of the importance of TMAO and urea in some cold water fishes, demonstrate that the synthetic machinery for these osmolytes is present in the liver, and suggest that the elevated levels in response to cold may be due to conservation rather than to increased production.