1. The effect of cobalamin deficiency on whole body cobalamin content and its turnover was examined in the rat. Quantitative and qualitative changes in hepatic cobalamin were also followed and the effect of deficiency on the turnover of this cobalamin was determined in the isolated perfused liver.
2. As cobalamin deficiency developed after total gastrectomy, whole body cobalamin content declined at a constant rate, indicating no attempt to conserve total body cobalamin stores even when depleted (5% of normal).
3. In contrast, the cobalamin concentration of liver declined more slowly, indicating conservation of hepatic cobalamin. Furthermore, the methylcobalamin (Me Cbl) content of liver was maintained or even increased.
4. Measurement of the rate of release of cobalamin by the isolated perfused liver at varying times after gastrectomy showed that as depletion of whole body and hepatic cobalamin stores proceeded, the rates of release of hepatic cobalamin into plasma and bile decreased. Regression analysis showed that the fractional rates of release of hepatic cobalamin into plasma (r = 0.9, P < 0.001, n = 15) and bile (r = 0.65, P<0.01, n = 15) were significantly correlated with hepatic cobalamin content.
5. It is concluded that conservation of hepatic cobalamin in deficiency is achieved, at least in part, by a specific decrease in the rate of release of hepatic cobalamin.