A B S T R A C T Previous studies have shown that plasma transcobalamin II (TCII) facilitates the cellular uptake of [57Co]vitamin B13 (Be) by a variety of tissues, but the lack of an intrinsic label on the protein moiety of the TCII-Bn complex has made it impossible to determine the role and fate of TCII during this process. We have labeled homogeneous rabbit and human TCII with 'I-labeled N-succinimidyl-3-(4-hydroxyphenyl) propionate and have performed in vivo experiments in rabbits.When 'M-labeled rabbit TCII-['"Co] B1s and 'I-labeled bovine albumin were simultaneously injected intravenously, we observed that 'I and 'Co were cleared from plasma at a faster rate (ti = 11 h) than 'I and that 12J and 57Co were present in excess of 'I in the kidney, liver, spleen, heart, lung, and small intestine j h after injection. Later, "7Co remained in excess of PI, but the ratio of 'I to 'I decreased progressively in all of these tissues; 'I fragments (mol wt less than 1,000) appeared in the plasma and were rapidly excreted in the urine. After 1 h following injection, 'Co was present in excess of 'I in the plasma. Additional experiments revealed that both isotopic moieties of human TCII-Bn were cleared from rabbit plasma 30% faster than their rabbit TCII-Bn3 counterparts and that apo-rabbit TCII and apo-human TCII were cleared from rabbit plasma 30% faster than holo-rabbit TCII and holo-human TCII, respectively.These studies, and appropriate control experiments, indicate that TCII and the TCII-Bu2 complex are cleared

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