Serum Binding of Vitamin B₁₂ Analogues: Identification of Binding Groups in the B₁₂ Molecule*

The Effect of Anticoagulants on the in vitro Binding Capacity of Serum and Plasma for Cobalamins

“…Limitations to the significance of results obtained by these methods are that the capacity to bind varies with the amount of cobalamin added (Berchter & Meyer 1957, Weinstein et al 1959, Meyer et al 1963) and that different techniques may give different results (Rosenthal et al 1962).…”

The Plasma Disappearance of Radioactive Cyanocobalamin: Effect of Prior Administration of Vitamin B12 Analogues

“…There are several possible reasons for this effect of hydroxocobalamin. It has been shown that hydroxocobalarnin binds considerably more tenaciously to plasma proteins than does cyanocobalamin (Meyer et al, 1963). The physiologic sigdcance of this finding is questionable, however, since these are in vitro studies and performed with massive doses of BIZ.…”

Serum Protein Binding of Vitamin B1212

“…Meyer and his co-workers (Meyer et al 1963) investigated the vitamin BI2 binding capacity of various analogs of vitamin Blz at different levels of added vitamin B12. They measured binding capacity of serum for radioactive hydroxocobalamin, and also assessed the effect of prior addition of nonradioactive cyanocobalamin.…”

“…In reviewing the several methods below, it will be apparent immediately that there are marked variations in the detail of these techniques, and the physical conditions of the in vitro experiments. The same technique was used, with a change of isotope to Cob?cyanocobalamin, for the studies of the effect of vitamin B12 analogs on serum binding of the vitamin (Meyer et al 1963). A study in which an assessment was sought of the numerous variables in the dialysis method is referred to below (Beal 1964).…”

“…Radioactive isotopes of vitamin BIZ have been available for biological use for sixteen years (Heinle et al 1952), but they have not led to rapid elucidation of the details of the transport and metabolism of the vitamin for several reasons. First, circulating vitamin BIZ, when present in physiological quantities, is not easily measured either by microbiologic or isotopic means; second, the vitamin has a number of analogs which show variation in binding properties and physiologic activity (Glass, 1962, Meyer et al 1963, Schiffer et al 1966, and it is stiIl not certain which one (or ones) of these is the metabolically significant form; third, the manner of serum protein binding and transport within the circulation are more complex than the patterns observed with most other plasma proteins concerned with transport, e. g., transferrin (Jandl & Katz 1963), caeruloplasmin (Sternlieb et al 1961), insulin (Kipnis & Stein 1964), penicillin (Kunin 1965), and bilirubin (Ode11 1959); fourth, the absolute amount of protein required to bind all circulating vitamin BI2 is so small (Heller et al 1964, ) that isolation of the binders has so far proven impossible, in spite of the increasingly precise techniques of protein chemistry available. Furthermore, incomplete knowledge of the normal mechanisms makes more difficult the precise understanding of variations in vitamin BIZ metabolism observed in certain disease states, such as vitamin B12 deficiency, and the myeloproliferative diseases.…”