The aim of the present study was to elucidate the mechanism of the
vitamin B(12) deficiency-induced changes of the
serine dehydratase (SDH) and
tyrosine aminotransferase (TAT) activities in the rat liver. When rats were maintained on a
vitamin B(12)-deficient diet, the activities of these two
enzymes in the liver were significantly reduced compared with those in the B12-sufficient control rats (SDH 2.8 (sd 0.56) v. 17.5 (sd 6.22) nmol/mg
protein per min (n 5); P < 0.05) (TAT 25.2 (sd 5.22) v. 41.3 (sd 8.11) nmol/mg
protein per min (n 5); P < 0.05). In the B(12)-deficient rats, the level of SDH induction in response to the administration of
glucagon and
dexamethasone was significantly lower than in the B(12)-sufficient controls.
Dexamethasone induced a significant increase in TAT activity in the primary culture of the hepatocytes prepared from the deficient rats, as well as in the cells from the control rats. However, a further increase in TAT activity was not observed in the hepatocytes from the deficient rats, in contrast to the cells from the controls, when
glucagon was added simultaneously with
dexamethasone. The
glucagon-stimulated production of cAMP was significantly reduced in the hepatocytes from the deficient rats relative to the cells from the control rats. Furthermore, the
glucagon-stimulated
adenylyl cyclase activity in the liver was significantly lower in the deficient rats than in the controls. These results suggest that
vitamin B(12) deficiency results in decreases in SDH and TAT activities correlated with the impairment of the
glucagon signal transduction through the activation of the
adenylyl cyclase system in the liver.