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.
Pezacka
E H
EH
Department of Laboratory Hematology, Cleveland Clinic Foundation, Ohio 44195.
Jacobsen
D W
DW
Luce
K
K
Green
R
R
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