Isolated hepatocytes from the little skate (Raja erinacea) are characterized by a general low metabolic activity, which can be explained by the benthic lifestyle of the animal. Of the substrates tested, alanine, serine, and leucine are equally good oxidative substrates, and the highest rates of gluconeogenesis are achieved with alanine and glycerol as carbon sources. In both respects, lactate is a relatively poor substrate, and this probably reflects the low abundance of this potential energy source in the skate, even after bouts of anaerobic exercise. The long chain fatty acid oleate and glycerol are poor oxidative substrates for the hepatocytes. Experiments with 3-mercaptopicolinate, an inhibitor for phosphoenolypyruvate carboxykinase (PEP CK), reveal that serine is funneled into gluconeogenesis through the serinetransaminase pathway, and PEP CK is bypassed. In vitro, the skate liver cells display the potential to synthesize and export ketone bodies from precursors such as leucine or oleate, whereas added P-hydroxybutyrate is poorly oxidized.The skate liver appears to be geared towards export of ketone bodies while at the same time conserving glycerol carbon for lipid synthesis. Supplied with precursors such as bicarbonate, glutamine, and aspartate, the cells synthesize urea at a rate of 0.85 fimol/g/hr at 10°C. /3-Hydroxybutyrate can accelerate the rate of urea synthesis, probably by increasing the intramitochondrial availability of ATP. Unlike any other vertebrate kidney, the tissue of the little skate appears to play no role in glucose synthesis. Skate kidney is characterized by an active oxidative metabolism and a broad substrate preference, with lactate, serine, alanine, and @-hydroxybutyrate serving as equally good oxidative fuels.Elasmobranch fishes possess a number of metabolic features that make this ancient group of vertebrates ideal objects of study for evolutionary biologists and comparative physiologists alike. These unique features include the specific synthesis and use of urea as an osmoregulatory agent (Smith, '361, the maintenance of trimethylamine-N-oxide (TMAO) as an important osmolyte (Pang et al., '77), and the apparent lack of albumin synthesis in many species (Sulya et al., '61). Furthermore, a variety of metabolic traits sets the elasmobranchs apart from most other vertebrates: Elasmobranchs are generally osmoconformers; they appear to regulate the concentration of blood glucose even more poorly than teleost fishes (deRoos et al., '85); their blood is almost devoid of free fatty acids (Plisetskaya, '80) Since our interests lie with the elucidation of liver cell metabolism in the lower vertebrates, with special emphasis on teleost fishes, we became interested in the elasmobranchs as a substantially different model Address reprint requests to Thomas P. Mommsen, who is now
