Analogues of vitamin B12 which appear to be noncobalamin corrinoids appear to be present in human red cells, liver, and brain. Their sources, nature, and effects require study, particularly with reference to their positive and/or negative effects on vitamin B12 metabolism. In normal persons, they are concentrated in liver, with only small quantities in red cells and still smaller quantities in brain. Their concentrations in disease states will be of interest, particularly in persons with varying degrees of neurological damage associated with deficiencies in vitamin B12 or analogue metabolism.
Elevated levels of parathyroid hormone-related protein (PTHrP) in hypercalcemic my-eloma patients were demonstrated in recent reports, suggesting that PTHrP behaves as a humoral mediator of hypercalcemia in myeloma. Herein we describe a hypercalcemic myeloma patient with a high serum PTHrP level. Moreover, the PTHrP level in the super-natant of bone marrow aspirates was about twofold of that in serum. Reverve transcrip-tase-polymerase chain reaction analysis showed PTHrP m-RNA in bone marrow containing myeloma cells. After chemotherapy, the concentrations of calcium and PTHrP decreased and PTHrP mRNA in bone marrow became undetectable. We conclude that PTHrP released by myeloma cells acted as the main bone resorption stimulating factor in this case. Am.
It is now known that nonphysiological cobalamin analogs exist in the gastrointestinal tract, but their metabolic behavior is unclear. In this study, [57Co]cobinamide was used to study its affinity to hog intrinsic factor-cobalamin (IF-Cbl) receptor which has no species specificity against human IF-Cbl receptor, and its relation to human saliva R binder. Cobinarnide was prepared from [57Co]cyanocobalamin and separated by paper chromatography. Human IF-Cbl complex was bound to IF-Cbl receptor but free cyanocobalamin was not. Although R binder-cobinamide was not bound to the IF-Cbl receptor, free cobinamide was bound to the IF-Cbl receptor to a significant extent (about one-half of IF-cyanocobalamin binding to the IF-Cbl receptor). We then investigated the binding of cobinamide to R binder and trypsin-treated R binder. Association constant of cobinamide binding to the IF-Cbl receptor was 1 .O X lo9 M-' which was much lower than that of cobinamide binding to trypsin-treated R binder and to untreated R binder. Further study indicated that cobinamide binding to the IF-Cbl receptor was blocked by the addition of R binder and also by trypsin-treated R binder. We conclude that one of the roles of R binder is to prevent binding of free cobalamin analogs to the IF-Cbl receptor in the gut. o
Fruit bats are an animal model for the neurologic damage which occurs in vitamin B,,-deficient humans. Cobalamin (vitamin BIZ) analogs were not detected in the plasma of fruit bats treated with nitrous oxide (N,O), which inactivates cobalamin. This observation does not lend support to the suggestion that the neurological changes associated with cobalamin inactivation by N,O andor cobalamin deficiency per se may be related to the accumulation of cobalamin analogs. However, although the plasma of control fruit bats lacked analogs, we did find analogs in their livers, at levels about 10% of total liver corrinoids, similar to human liver analog levels. 88
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