In vivo fate of hemopexin and heme-hemopexin complexes in the rat.
The disposition in the rat of the plasma heme-binding protein hemopexin (Hx), as the native apoprotein and as its heme complex (HHx), has been studied using the residualizing protein label dilactitol-125I-tyramine (*I-DLT). The aim of this work was to identify the tissue sites of Hx uptake and catabolism, independent of heme binding, and to evaluate how heme loading affects Hx catabolism at these sites. *I-DLT-Hx had a circulating half-life of approximately 1.2 days and was recovered in degraded form in comparable amounts in visceral (liver, kidney, spleen) and peripheral (skin, muscle) tissues, indicating a generalized diffuse catabolism of the protein throughout the body. The plasma half-life of *I-DLT-Hx injected as a preformed heme-Hx complex was the same as that of the apoprotein; however, injection of the complex resulted in about a twofold increase in hepatic degradation of Hx. The lack of an effect of heme on overall catabolism of the preformed HHx complex was consistent with the approximately 1-h half-life of heme, injected as 14C-heme-Hx, in the circulation; however, as much as 20-fold more 14C-heme than Hx protein was recovered in liver from 14C-heme-Hx. The absolute amount of *I-DLT-Hx degraded in liver was significantly increased when heme was injected in excess of the heme binding capacity of circulating Hx, while 131I-DLT-albumin catabolism in liver was unaffected. Thus, depending on the physiological conditions studied, the data are consistent with a model in which, following hepatic uptake of heme from HHx, varying proportions of the protein are either returned to the circulation or degraded in the liver.
Potter
D
D
Department of Chemistry and Biochemistry, School of Medicine, University of South Carolina, Columbia 29208.
Chroneos
Z C
ZC
Baynes
J W
JW
Sinclair
P R
PR
Gorman
N
N
Liem
H H
HH
Muller-Eberhard
U
U
Thorpe
S R
SR
D000818:Animals; D005260:Female; D006418:Heme / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D006466:Hemopexin / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D006418:Heme; D006466:Hemopexin