Atypical cobalamin binding in the serum of congenital deficiency of transcobalamin II

Abstract

The serum cobalamin (Cb 1) binding patterns were described in nine children with congenital deficiency of transcobalamin II (TC II). Immunoreactive TC II was less than 100 pg/ml TC II-Cb 1 equivalent in eight and 150 pg/ml in the ninth. There was neither endogenous TC II-Cb 1 (holo TC II) nor apo TC II. Thus, the defect was characterized by the absence of any binding of Cb 1 to TC II either in vivo or in vitro and either non-detectable or much reduced immunoreactive TC II. Only the serum from an untreated infant bound any added Cb 1 at all, but in every sera there was binding of endogenous Cb 1 to a substance of the molecular size of albumin. Native Cb 1 was also bound to R binder and in some instances was incorporated into large complexes. The precise nature, cause and consequences of this atypical binding are unknown.

High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep

“…Five grams of Hydroxocobalamin, corresponding to 10 6 times the recommended daily intake, can drop the concentration of soluble H 2 S to almost zero during infusion of moderate to severe levels of H 2 S infusion (4). This observation supports the view that Hydroxocobalamin or other Vitamin B12 analogues (11), could exert a protective effect against H 2 S toxicity since not only can they diffuse within cells (12) via non-transcobalamin mechanisms (13–15), but they also oppose the effects of Nitric oxide (16–19), recently shown to potentiate the effects of H 2 S (20, 21). Finally, intravenous infusion of large dose of Hydroxocobalamin is already FDA approved for the treatment of cyanide poisoning (22, 23).…”

Transcobalamin II Mediated Delivery of Albumin-Bound Hydroxocobalamin to Human Liver Cells

“…Albumin in human serum may contain small amounts of endogenous Cbl, but it is difficult to accurately quantify in the presence of the Cbl bound to R and TCII. It is more easily identified in patients who lack R or TCII and after treatment with pharmacological doses of OH-Cbl (18)(19)(20). R-binder, TCII, and albumin differ greatly in their affinities for OH-Cbl (4, 2 1).…”

Inheritance of transcobalamin II (TC II) in two families with TC II deficiency and related immunodeficiency

“…Case I: B.A., ~--Clinical details of this TC II-deficient patient have been described extensively (Hitzig et al, 1974;Hall et al, 1979;Frfiter-Schr6der et al, 1981). Impairment of haematopoietic function, defective antibody synthesis and agammaglobulinaemia were correctable with vitamin Blz administration.…”

“…Reduced TC II serum levels in healthy relatives and tack of apo-and holo-TC II in the TC II-deficient patient (Hall et at., 1979) indicate that congenital deficiency is inherited as an autosomal recessive trait. TC II can be split up into isoproteins by polyacrylamide gel electrophoresis (Fr~tter-Schr6der et al, 1979a).…”