Hemopexin-mediated heme transport to the liver. Evidence for a heme-binding protein in liver plasma membranes.
Isolated liver plasma membranes interact with heme-hemopexin and effect the removal of heme from the complex. This heme is rapidly accumulated by a previously undescribed heme-binding membrane component (HBC). This intrinsic membrane component can be solubilized from the membrane with Triton X-100 in a form that retains the ability to bind heme. Solubilized HBC was shown to be distinct from hemopexin itself, free heme, ligandin, globin, heme oxygenase, cytochrome P-450, and albumin. Since formation of the heme-HBC complex is effected by the interaction of heme-hemopexin with its receptor, HBC may either be a subunit of the heme-hemopexin receptor or a separate protein that interacts with the receptor. HBC can also bind heme (Kd apparent 200 nM) that is presented to it in a nonprotein bound form, showing true heme-binding activity. HBC is proteinaceous since treatment with proteases, heat, and disulfide bond reducing agents diminishes its ability to bind heme. HBC and any associated detergent elutes from Sephacryl S-200 with an apparent molecular weight of 115,000 and Stokes radius of 7.5 nm. This component, which may comprise 0.5% of liver plasma membrane protein, appears to have an acidic pI since it adsorbs to DEAE-cellulose at pH 7.4 but not to CM-cellulose at pH 6.4. In sucrose gradients, HBC migrates with S values of 1.69 and 4.02, suggesting that it has subunits or that it forms multimers under these conditions.
D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000032:analysis*; D002462:Cell Membrane / Q000032:analysis; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D006466:Hemopexin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D011817:Rabbits; D013696:Temperature; D014357:Trypsin / Q000378:metabolism
D002352:Carrier Proteins; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D006418:Heme; D006466:Hemopexin; D006419:Heme Oxygenase (Decyclizing); D010447:Peptide Hydrolases; D014357:Trypsin