Vitamin B12 deficiency results in the abnormal regulation of serine dehydratase and tyrosine aminotransferase activities correlated with impairment of the adenylyl cyclase system in rat liver.
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.
Ebara
Shuhei
S
School of Human Science and Environment, University of Hyogo, Himeji, Hyogo 670-0092, Japan. ebara@shse.u-hyogo.ac.jp
Nakao
Motoyuki
M
Tomoda
Mayuko
M
Yamaji
Ryoichi
R
Watanabe
Fumio
F
Inui
Hiroshi
H
Nakano
Yoshihisa
Y
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D004032:Diet; D005934:Glucagon / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D012695:L-Serine Dehydratase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014444:Tyrosine Transaminase / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000201:enzymology*
D003907:Dexamethasone; D005934:Glucagon; D000242:Cyclic AMP; D014444:Tyrosine Transaminase; D012695:L-Serine Dehydratase; D000262:Adenylyl Cyclases; D014805:Vitamin B 12