Purified radiolabeled antithrombin III metabolism in three families with
hereditary AT III deficiency: application of a three-compartment model
EA Knot, E de Jong, JW ten Cate, AH Iburg, CP Henny, T Bruin and J Stibbe
Purified human radioiodinated antithrombin III (125I-AT III) was used to
study its metabolism in six members from three different families with a
known hereditary AT III deficiency. Six healthy volunteers served as a
control group. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
(SDS-PAGE) and crossed immunoelectrophoresis (CIE) showed the purified AT
III to be homogeneous. Amino acid analysis of the protein revealed a
composition identical to a highly purified internal standard. The specific
activity was 5.6 U/mg. Analysis of plasma radioactivity data was performed,
using a three-compartment model. Neither plasma disappearance half-times
nor fractional catabolic rate constants differed significantly between
patients and control subjects. The mean absolute catabolic rate in the
patient group was significantly lower than that of the control group at
2.57 +/- 0.44 and 4.46 +/- 0.80 mg/kg/day, respectively. In addition, the
mean patient alpha 1-phase, flux ratio (k1,2 and k2,1) of the second
compartment alpha 2-phase and influx (k3,1) of the third compartment were
significantly reduced as compared with control values. It has been
tentatively concluded that the observed reduction in the second compartment
may be caused by a decrease in endothelial cell surface binding.
Volume 67,
Issue 1,
pp. 93-98,
01/01/1986
Copyright © 1986 by The American Society of Hematology
