Alpha-1-antitrypsin. Plasma survival studies in the rat of the normal and homozygote deficient forms.
Alpha-1-antitrypsin from normal individuals (Pi type MM) from those with an inherited deficiency of circulatory protein (Pi type ZZ) were labelled with 125I and plasma clearance rates measured in rats either prior to, or following treatment with neuraminidase to remove terminal sialic acid residues. In addition, these proteins and the derivatives were tested for their ability to bind to an hepatic binding protein obtained from rabbit liver membranes that has been shown to be responsible for the clearance of serum asialoglycoproteins. Finally, the two native forms of alpha-1-antitrypsin were treated with galactose oxidase followed by reduction with tritiated potassium borohydride and then analyzed for tritium incorporation in the neutral sugar fraction. The results indicate: (a) clearance from plasma for both forms of alpha-1-antitrypsin is dramatically enhanced upon the loss of terminal sialic acid residues to the liver membrane protein; (b) Z protein does not exhibit terminal galactosyl residues; (c) the low level of Z protein in plasma cannot be accounted for by a faster rate of clearance relative to M protein. The relevance of these findings to the alpha-1-antitrypsin deficiency state are discussed.
D000818:Animals; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D051381:Rats; D012794:Sialic Acids; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency
D012794:Sialic Acids; D000515:alpha 1-Antitrypsin