Glial cells as a model for the role of cobalamin in the nervous system: impaired synthesis of cobalamin coenzymes in cultured human astrocytes following short-term cobalamin-deprivation.
The conversion of cyanocobalamin to adenosyl- and methylcobalamin is impaired in cobalamin-deficient cultured human glial cells. In contrast cultured human skin fibroblasts retained their ability to synthesize coenzyme forms when grown in cobalamin-deficient medium. Cells were pre-conditioned by growing in cobalamin-deficient media for six weeks and then subcultured in medium containing either free or transcobalamin II-bound 57Co-cyanocobalamin. Although both coenzyme levels were low in cobalamin-deficient glial cells, the decrease in methylcobalamin was more marked than that of adenosylcobalamin. Methionine synthase and Cb1 reductase activities were markedly decreased in cobalamin-deficient glial cells but were unchanged in fibroblasts cultured in cobalamin-deficient medium. Our data suggest that in glial cells, cobalamin coenzyme synthesis and function is exquisitely sensitive to short-term cobalamin deprivation. Glial cells apparently synthesize and secrete transcobalamin II since antibodies directed against the transport protein inhibit the uptake of free cobalamin.
Department of Laboratory Hematology, Cleveland Clinic Foundation, Ohio 44195.
E H
EH
Pezacka
D W
DW
Jacobsen
K
K
Luce
R
R
Green
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D001254:Astrocytoma; D001692:Biological Transport; D002460:Cell Line; D002461:Cell Line, Transformed; D003037:Cobalt Radioisotopes; D006801:Humans; D007700:Kinetics; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D014155:Transcobalamins / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*
D003037:Cobalt Radioisotopes; D014155:Transcobalamins; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12