Transport and metabolism of bromosulfophthalein by isolated rat liver cells.

Kinetics of transport and metabolism of bromosulfophthalein have been studied in isolated liver cells in a dose-dependent manner obtaining the following results. The disposition of bromosulfophthalein in suspensions of isolated liver cells is similar to the turnover in the whole liver. The initial maximal rate of uptake of bromosulfophthalein is 2--3 times faster than intracellular conjugation with glutathione. Conjugation proceeds to an equilibrium between intracellular substrate (bromosulfophthalein) and product (bromosulfophthalein-glutathione conjugate) which are both transiently accumulated in the cell. Formation of bromosulfophthalein-glutathione is accompanied by an equimolar decrease of glutathione. The bromosulfophthalein-glutathione conjugate is slowly released from the cells in an energy-dependent and saturable transport process. The maximal velocity of excretion amounts to only 6% of the maximal velocity of uptake and to 20% of the maximal velocity of conjugation. Excretion, therefore, represents the slowest step in the overall turnover.