Extremely low activity of methionine synthase in vitamin B-12-deficient rats may be related to effects on coenzyme stabilization rather than to changes in coenzyme induction.
Severely vitamin B-12 (B-12)-deficient rats were produced by feeding a B-12-deficient diet. The status of B-12 deficiency was confirmed by an increase in urinary methylmalonate excretion and decreases in liver B-12 concentrations and cobalamin-dependent methionine synthase activity. Rat liver methionine synthase existed almost exclusively as the holoenzyme. In B-12-deficient rats, the level of methionine synthase protein was lower, although the mRNA level was not significantly different from that of control rats. When methylcobalamin, the coenzyme for methionine synthase, was administered to the B-12-deficient rats, growth, liver B-12 concentrations and urinary excretion of methylmalonate were reversed although not always to control (B-12-sufficient) levels in a short period. During this recovery process, methionine synthase activity and its protein level increased, whereas the mRNA level was unaffected. We reported previously that rat apomethionine synthase is very unstable and is stabilized by forming a complex with methylcobalamin. Thus, the extremely low activity of methionine synthase in B-12-deficient rats may be related to effects on "coenzyme stabilization" (stabilization of the enzyme by cobalamin binding) rather than to changes in "coenzyme induction."
Faculty of Engineering and. Faculty of Education, Okayama University, Japan.
K
K
Yamada
T
T
Kawata
M
M
Wada
T
T
Isshiki
J
J
Onoda
T
T
Kawanishi
A
A
Kunou
T
T
Tadokoro
T
T
Tobimatsu
A
A
Maekawa
T
T
Toraya
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004795:Enzyme Stability; D005260:Female; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014155:Transcobalamins / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000201:enzymology*
D012333:RNA, Messenger; D014155:Transcobalamins; D008764:Methylmalonic Acid; C019476:mecobalamin; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12