Interaction of potentially toxic bile acids with human plasma proteins: binding of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid to lipoproteins and albumin.
The binding of lithocholic acid to different plasma fractions was studied. When whole plasma was incubated for 8 hr, approximately 25% of the incubated [14C]lithocholic acid was bound to the lipoprotein and lipoprotein-free, albumin-rich fractions. An average of 87.6% of the bound-lithocholic acid was present in the lipoprotein-free, albumin-rich fraction, 7.2% in high density lipoproteins, 2.2% in low density lipoproteins, 1.0% in intermediate density lipoproteins and 2.0% in very low density lipoproteins. Expressed as binding per microgram protein, considerably less [14C]lithocholic acid was bound to the lipoprotein-free, albumin-rich fraction, than to the lipoproteins. The binding of [14C]lithocholic acid after the incubation of the isolated plasma fractions was similar to that found after the incubation of whole plasma. The highest transfer of [14C]lithocholic acid occurred from the lipoprotein-free, albumin-rich fraction to the lipoprotein fractions. The studies indicate, that, although the largest amount of lithocholic acid is bound to the lipoprotein-free, albumin-rich fraction, per microgram protein, the binding of lithocholic acid to lipoproteins is more pronounced and stable than that bound to the lipoprotein-free, albumin-rich fraction. Since lipoproteins, in contrast to albumin, are internalized by most tissues, they may be important carriers into cells of lithocholic acid and other potentially toxic or tumorigenic bile acids.
Malavolti
M
M
Department of Medicine, George Washington University Medical Center, Washington, D.C. 20037.
Fromm
H
H
Ceryak
S
S
Shehan
K L
KL
D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000378:metabolism*; D008095:Lithocholic Acid / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
D008074:Lipoproteins; D012709:Serum Albumin; D008095:Lithocholic Acid