The in vitro interaction of human apolipoprotein A-I and high density lipoproteins

Radioiodinated human apolipoprotein A-I, when incubated with plasma lipoproteins, associates exclusively with high density lipoproteins. It does not interact with very low density lipoproteins or low density lipoproteins. Binding is rapid, being complete within 10 min, and is not affected by variation of pH within the range 6.0-9.5 or of temperature over the range 0°-37°C. At equimolar concentrations of apolipoprotein A-I and high density lipoproteins, 0.58 mol of the apoprotein bind per mol of high density lipoproteins. Binding increases progressively with apolipoprotein A-I concentration up to an apolipoprotein A-I : high density lipoprotein molar ratio of 20 : 1, when each mol of lipoprotein binds 7.62 mol of apoprotein. Interaction of apolipoprotein A-I with high density lipoproteins displaces endogenous apolipoprotein A-I from the particle to a maximum of 2 mol of apolipoprotein A-I per mol of high density lipoproteins. This displacement occurs at an apoprotein : lipoprotein molar ratio of 10 : 1. The rest of the endogenous apolipoprotein A-I is not displaceable, even when the exogenous apoprotein : lipoprotein ratio is increased to 20 : 1. Incubation of apolipoprotein A-I and high density lipoproteins at molar ratios of 0.3 or less results in a mol for mol exchange of exogenous with endogenous apolipoprotein A-I on the lipoprotein. The half-life of ¹³¹I-labeled apolipoprotein A-I/high density lipoproteins in rats and rabbits is 15 h and 1.40 days respectively; the material decays exponentially from the bodies of these animals. More than 94% of the radioactivity in their plasma is associated with a component of hydrated density 1.063-1.21 kg/l. When injected into humans, the radioiodinated apoprotein incorporated into high density lipoproteins by in vitro incubation is cleared from the plasma 20% faster than endogenous apolipoprotein A-I in high density lipoproteins.