Catabolic rate of α1-antitrypsin of Pi type M and Z in man

Abstract

1. Human alpha1-antitrypsin was isolated from three Pi M and two Pi Z subjects without alteration of its microheterogeneity. The purified proteins were labelled with either 125I or 131I by a lactoperoxidase method. 2. The disappearance rate of two types of alpha1-antitrypsin were studied after simultaneous injection of labelled M-protein and Z-protein into Pi M subjects. 3. The ratio of extravascular to plasma pools of alpha1-antitrypsin ranged between 1-2 and 1-6 with no difference between M- and Z-protein. The mean fractional catabolic rates of M-protein and Z-protein were respectively 0-26 and 0-40 per day. 4. The difference in catabolic rate of Z- and of M-protein is too small to explain why the alpha1-antitrypsin content of the blood in Pi ZZ subjects is only 15% of that normally found in Pi MM subjects. The low alpha1-antitrypsin in Pi ZZ subjects appears mainly to be due to a low rate of biosynthesis.

Turnover of autologous? 1-antitrypsin in a patient with congenital analbuminemia

“…The plasma volume of our patient was normal, thus excluding the possibility that a smaller volume of distribution is the reason for the high 0q-antitrypsin concentration. The halflifes of 7,5 and 8 days found for the normal volunteers compare well with those of 6.0-7.2 days found by Laurell and coworkers for 0q-antitrypsin of the same phenotype [10]. In our patient, the half-life was prolonged to 15 days.…”

Multiple tissues express alpha 1-antitrypsin in transgenic mice and man.

“…Although human PiM livers normally synthesize sufficient AAT to maintain plasma levels at 1.35 g/liter (31) with a t1/2 of 32 (34). The number of AAT-positive cells was correlated with gene copy number and plasma AAT levels.…”

Design and characterization of an APC-specific serpin for the treatment of hemophilia

“…49 In addition, in contrast to current bypassing agents, which are administered intravenously, the subcutaneous route of administration for KRK a 1 AT might also be available. Studies in rabbits showed that the pharmacodynamics of subcutaneously administered plasma human a 1 AT were comparable to intravenously administrated protein.…”