Catabolism of desialylated human plasma alpha1-antitrypsin and its trypsin complex in the rat.

Human plasma α₁-antitrypsin (α₁-AT) was labeled with either ³H ³H-labeled NANA (N-acetyl-neuraminic acid)-7] residues in the carbohydrate moiety) or ¹⁴C (?-N-methyl-¹⁴C]lysyl residues in the protein backbone) or with both isotopes in the corresponding residues. After intravenous injection into rats of the doubly labeled partially (50%) desialylated (methyl-¹⁴C]·³H]NANA-7)-α₁-AT, the rates of disappearance from the plasma of both isotopes were very rapid and yielded essentially the same circulatory half-life of 5 min. The rapid disappearance of the doubly labeled glycoprotein from the plasma was accompanied by concomitant fast and equal accumulations of ¹⁴C and ³H in the liver which constituted about 70% of the administered dose 15 min after the injection. The asialo (methyl-¹⁴C])-α₁-AT·trypsin complex or methyl-¹⁴C]-α₁-AT·trypsin complex had a plasma survival time (45 min) that was intermediate between methyl-¹⁴C]-α₁-AT and its desialylated derivative. These complexes were removed from the plasma by the liver (45% of the injected dose 60 min after injection), although not as rapidly as asialo (methyl-¹⁴C])-α₁-AT. Blockade of the reticuloendothelial (Kupffer) cells by simultaneous injection of heat-denatured albumin inhibited the liver uptake of the inhibitor·trypsin complexes but not that of the uncomplexed asialo α₁-AT. Radioactive ?-N,N-dimethyllysine, ?-N-monomethyllysine, methionine, choline, and betaine were separated and identified from the trichloro-acetic acid-soluble fraction of rat livers 25 min after injection of asialo (methyl-¹⁴C])-α₁-AT.