Albumin-bilirubin binding mechanism.
After binding of bilirubin to human serum albumin (1:1), a train of relaxational changes of conformation takes place. The late part of these processes, occurring in the time interval 1-500 s, has been studied by recording the changes of light absorption. Similar processes have been demonstrated after binding of fatty acid anion to the bilirubin-albumin complex as well as after a pH-jump from 6 to 9. Solvent perturbation spectra obtained on the addition of 20% sucrose have failed to demonstrate exposure of the bilirubin chromophores in the complex to the surrounding medium. Xanthobilirubinate which has a single dipyrrolic chromophore compared to the two of bilirubin is bound to albumin in competition with bilirubin, as concluded from co-binding studies with monoacetyldiaminodiphenylsulfone and diazepam, probing two different binding functions of the albumin molecule. Late conformational changes were absent after binding of xanthobilirubinate. Binding of fatty acid to the complex and a pH-jump did not affect the spectrum of xanthobilirubinate-human serum albumin. The findings can be explained by a model, previously proposed, in which the late spectral changes are affected by rotation of one half-domain of albumin, binding one bilirubin chromophore, relative to another half-domain to which the second bilirubin chromophore is bound, whereby a change of exiton splitting occurs. Such changes are not seen with the complex of xanthobilirubinate and albumin, since only a single chromophore is present.
D001663:Bilirubin / Q000031:analogs & derivatives* / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007850:Lauric Acids / Q000378:metabolism; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013053:Spectrophotometry; D013395:Sucrose / Q000494:pharmacology
D007850:Lauric Acids; D012709:Serum Albumin; C030358:lauric acid; C013337:xanthobilirubic acid; D013395:Sucrose; D001663:Bilirubin