Metabolism of rabbit plasma-derived factor VII in relation to prothrombin in rabbits

In the human circulation, factor VII is present in relatively low plasma co ncentration (0.01 muM) and has been reported to have a short half-life (t(1 /2); 6 h). In contrast, prothrombin is present in a relatively high plasma concentration (2 muM) and has a relatively long catabolic half-life (t(1/2) = similar to2-3 days). This report examines the metabolic characteristics of purified rabbit plasma factor VII and prothrombin, radiolabeled with I-1 25 and I-131, respectively, in healthy young rabbits. From the plasma clear ance curves of protein-bound radioactivities, fractional catabolic rates an d compartmental distributions were calculated using a three-compartment mod el. Turnover of factor VII within the intravascular space (2.95 days) excee ded that of prothrombin (1.9 days). However, the whole body fractional cata bolic rate of factor VII (0.34 days(-1); catabolic t(1/2) = 2.04 days) was significantly slower than that of prothrombin (0.53 days(-1); t(1/2) = 1.31 days). Furthermore, the fractional distributions of factor VII in the intr avascular (0.14) and extravascular compartments (0.76) differed from those of prothrombin (0.29 and 0.53). Absolute quantities of factor VII and proth rombin catabolized by a 3-kg rabbit amounted to 0.18 and 24.0 mg/day, respe ctively (molar ratio of prothrombin to factor VII = 100). The molar ratio o f catabolism was compared with the release rates of factor VII and prothrom bin from rabbit livers perfused ex vivo. After correction for uptake of fac tor VII and prothrombin by the liver, the molar ratio of released prothromb in to factor VII in the perfusate was similar to 293:1 over a 0.25- to 3-h interval. These results indicate that, compared with prothrombin, factor VI I in the healthy rabbit circulates as a relatively long-lived protein. This behavior does not reflect that reported for factor VII in the human circul ation.