Trimethylamine oxide (TMAO) and urea levels in the blood of rainbow sm
elt, Osmerus mordax, were previously shown to increase dramatically in
winter, but the means by which these osmolytes are acquired has remai
ned 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 herri
ng, 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 (Macro-zoar
ces americanus, Eleginus gracilis, and Platichthys stellatus), and the
se results, together with previously reported data, suggest that TMA o
xidase activity is a necessary condition for high levels of TMAO in th
e blood. In the smelt, urea appears to be synthesized via uricolysis a
nd also through the action of arginase on dietary arginine, while the
ornithine urea cycle appears to be nonfunctional. There was no relatio
n among several species of northern fishes between levels of urea in t
he blood and levels of uricase or arginase activity. Together, these r
esults provide further evidence of the importance of TMAO and urea in
some cold water fishes, demonstrate that the synthetic machinery for t
hese osmolytes is present in the liver, and suggest that the elevated
levels in response to cold may be due to conservation rather than to i
ncreased production.