COBALAMIN BINDING AND UPTAKE INVITRO IN THE HUMAN CENTRAL NERVOUS-SYSTEM

  • 1 January 1981
    • journal article
    • research article
    • Vol. 97  (1) , 123-133
Abstract
The cobalamin-binding proteins of CSF and uptake of the vitamin by homogenates of CNS tissue were examined. CSF from 24 patients had a mean unsaturated cobalamin-binding capacity of 335 .+-. 282 pg/ml. The vast majority of this was TC [transcobalamin] II (302 .+-. 276 pg/ml). The remainder consisted of R binder and a binder eluting with the void volume on Sephadex G-200 gel chromatography. CSF TC II was identical to serum TC II immunologically, functionally, in molecular size and in electrophoretic mobility, but the levels of the 2 did not correlate. CSF TC II levels may correlate best with CSF protein levels and tended to be higher in abnormal fluids. Unlike serum TC II, CSF TC II tended to adhere to glass surfaces; uncorrected, this may be a source of artifact in studying various fluids. CSF contains little cobalamin, but most of the endogenous cobalamin was carried by TC II instead of by R binder. CSF appears to have a much higher total TC II:R binder ratio than does plasma. TC II enhanced 57CoB12 [radiolabeled cyanocobalamin] uptake by neonatal and adult human brain homogenate and by mouse brain homogenate. The primary phase of TC II-57CoB12 uptake in vitro by human brain cortex homogenate occurred mostly within 30 min and was maximal at 22.degree. C. Uptake was specific, but apo- and holo-TC II appeared to have equal affinity for the receptors. Spinal cord homogenate took up less TC II-57CoB12 per wet wt of tissue than did brain homogenate. R binders did not enhance cobalamin uptake, but inhibited it. Uptake of cobalamin by CNS tissue is apparently dependent on TC II and TC II may be even more prominent in cobalamin transport in the CSF than it is in plasma.