Uptake of monohydric alcohols by liver: demonstration of a shared enzymic space

Multiple-indicator dilution studies of the hepatic uptake of straight-chain C1-C5 monohydric alcohols were carried out in anesthetized dogs, with either no preceding or saturating infusions of ethanol, and at different steady-state levels for the C2 experiments. Labeled red cells were utilized as a vascular reference, and labeled water was used as a second reference entering liver cells. Kinetic analysis of the data provided estimates of both an uptake rate constant and the space of distribution available to label. From the decrease in the uptake rate constant for labeled ethanol with bulk concentration, we calculated a maximal removal rate of 0.025 mumol X s-1 X (ml liver water)-1 and a Michaelis constant (Km) of 0.32 mM. Especially for the labeled C3-C5 alcohols, a space in excess of that available to water was found, and the bulk of this was dissipated by ethanol infusion. The increment, the "shared enzymic space", which varies with enzymic concentration and inversely with Km, was used to calculate Km values for the other alcohols.