Mechanism of hepatocellular uptake of albumin-bound bilirubin.

摘要: We previously demonstrated that unconjugated bilirubin spontaneously diffuses through phospholipid bilayers at a rate which exceeds albumin dissociation, suggesting solvation from represents the rate-limiting step in hepatic clearance. To further examine this hypothesis, we studied uptake of bovine serum (BSA)-bound by cultured hepatoblastoma (HepG2) cells. Uptake was saturable, with K(m) and V(max) 4.2+/-0.5 microM (+/-S.E.M.) 469+/-41 pmol min(-1) mg(-1) 25 degrees C. Substantial also observed 4 C (K(m)=7.0+/-0.8 microM, V(max)=282+/-26 mg(-1)), supporting diffusional transport mechanism. Consistent reported rates, cellular bound to human more rapid than for BSA-bound bilirubin, indicative dissociation-limited uptake. Counterintuitively, an inverse correlation between pH flip-flop observed, due effects on dissociation membrane bilayer. The identification inflection point 8.1 is pK(a) value range. Taken together, our data suggest hepatocellular occurs principally mechanism involving spontaneous transmembrane diffusion.