Discrepancies in the catabolic pathways of human and rat high-density lipoprotein apolipoprotein A-I in the rat.
The in vivo metabolism in the rat of radioiodinated human and rat high-density lipoprotein was compared with a double-label procedure using 125I and 131I. While rat high-density lipoprotein showed a biphasic serum decay, human high-density lipoprotein was characterized by a monoexponential serum decay. No differences were observed between the serum decay of human high-density lipoprotein-2 and -3 subfractions, isolated by rate zonal ultracentrifugation. The catabolic sites of human and rat high-density lipoprotein were analysed using the lysosomal cathepsin inhibitor leupeptin. Radioiodinated rat high-density lipoprotein was catabolized by the kidneys and by the liver. In contrast, radioiodinated human high-density lipoprotein was catabolized almost exclusively in the liver. No difference in the catabolic sites of human high-density lipoprotein-2 and -3 subfractions was observed. The catabolic sites of human high-density lipoprotein apolipoprotein A-I in the rat were further analysed using the O-(4-diazo-3-[125I]iodobenzoyl) sucrose label. Compared with rat high-density lipoprotein apolipoprotein A-I, the kidneys played a minor role in the catabolism of human high-density lipoprotein apolipoprotein A-I. It is concluded that in the rat the catabolic pathways of the apolipoprotein A-I moieties of rat and human high-density lipoproteins are different, indicating that homologous high-density lipoproteins should be used for the investigation of in vivo metabolism.
D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D007976:Leupeptins; D008075:Lipoproteins, HDL; C032854:leupeptin