Biological activity of protein-bound calcium in serum

We have previously reported the existence of a subfraction of serum calcium that is tightly bound to normal human serum proteins. This tightly bound calcium fraction (TBC) is thought to be a calcium-albumin-fatty acid complex (ACP) because similar complexes can be prepared by the sequential addition of albumin to calcium in the presence of palmitic acid. These studies deal primarily with TBC from rat serum and the uptake of calcium by bone cells in palmitate-treated serum. It is reported that TBC does not exchange with ionized calcium and that calcium binds strongly to albumin in the presence of palmitate. The uptake of calcium in palmitate-treated serum is three times greater than the uptake of calcium in control serum in both in vitro and in vivo systems. These findings demonstrate that 1) a tightly bound albumin-calcium fraction is present in both human and rat sera; 2) calcium in TBC may be complexed to albumin via fatty acids; 3) TBC does not participate in the maintenance of the level of ionized calcium in serum and 4) circulating TBC or ACP complexes may be taken up by living cells.