Role of Albumin in Liver Uptake

We were very interested to read the selected summary by S. Erlinger (1) in a recent issue of GASTROENTEROLOGY, and we would like to make some remarks about the albumin problem.The first remark concerns the differences in the binding to albumin among the organic anions; bilirubin and bromuslfonphtalein are tightly and almost completely bound to the protein, whereas taurocholate is 42% bound (2).Among the various bile acids, moreover, strong differences exist, as lithocholate is 98% bound and dihydroxy bile acids average 50% albumin binding.Therefore, possibly, the effect of albumin, be what it may, differs from one anion to another and comparable results from experiments using different organic anions may be difficult.The second remark concerns differences in the hepatic uptake of fatty acids and taurocholate; fatty acids do not show saturation kinetics (3) when they are taken up by the liver in absence of albumin in the perfusion medium, whereas taurocholate uptake kinetics is saturable (4) also when taurocholate is perfused into the liver with a perfusion medium without albumin.This, in our opinion, strongly supports differences as to the role of albumin in the liver uptake of various substances.The third remark concerns the dissociation of the ligand: albumin complex near the cell surface.We actually do not know the rate of dissociation, and until we understand the determinants of the process itself, few conclusions can be drawn as to the uptake of the free from the bound ligand.Therefore, there are at least three possibilities for taurocholate uptake by the liver: (a) the liver takes up free taurocholate, (b) it takes up taurocholate bound to albumin, and (c) albumin inhibits (that is, retards) in some way the uptake of free taurocholate.We think that we have demonstrated (a) to be true, while others (3) have shown that (b) is true as well.About (cl.albumin may act either at the suggested albumin receptor level or by simply reducing free taurocholate available for uptake.