Abstract
Why is the serum α 1 -antitrypsin activity in the type ZZ (deficient) individual only one-tenth that of the type MM (normal) individual? To determine whether the explanation is simply decreased concentration or also decreased specific activity, the specific activity was determined for ZZ and MM sera. Four ZZ sera had a mean specific activity of 0.665±0.170 sd mg of trypsin inhibited per milliliter of serum and 20 MM sera had a mean specific activity of 0.573±0.157 sd. Hence the lower activity of ZZ serum is due entirely to its lower concentration of α 1 -antitrypsin. This lower concentration, in turn, could be due to decreased entry into or increased removal from the circulation. Increased removal in ZZ could be due to an increased intrinsic lability or to an accelerated removal mechanism. At acid pH (4.6–6.6) and at elevated temperatures (54–58 C), the activity of ZZ sera was not more labile than that of MM sera. An accelerated removal mechanism may also be unlikely in view of the reported finding that labeled α 1 -antitrypsin had the same removal rate when injected into an MM or a ZZ individual. If the lower concentration is not due to increased removal, it must be due to decreased entry into the circulation. This could be the result of a decreased rate of synthesis or secretion. The fact that antitrypsin accumulates in the hepatic parenchymal cells of the ZZ individual favors a defect in hepatic secretion.
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This work was supported by NIH-NHLI Contract No. 71-2221.
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Rowley, P.T., Sevilla, M.L. & Schwartz, R.H. Pathogenesis of deficient serum α1-antitrypsin in the type ZZ homozygote. Biochem Genet 12, 235–242 (1974). https://doi.org/10.1007/BF00486092
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DOI: https://doi.org/10.1007/BF00486092