Metabolic Studies of Human Fibrinogen ‘y/’y’ Chain Heterogeneity

Human fibrinogen chromatographed on DEAE-cellulose resolves into two components containing 85% (peak 1 ) and 15% (peak 2) of the total fibrinogen. Peak 1 and peak 2 differ only in the composition of their ‘y chains, with peak 1 containing only one type of “y chain and peak 2 containing equal amounts of ‘y chain and a second chain, called ‘y’. In an effort to explain the difference in the amount of peak 1 compared to peak 2. metabolic studies were performed with radiolabeled peak 1 and peak 2 in two normal subjects. Autologous peak 1 and peak 2 fibrinogen were pooled separately, rechromatographed, labeled with ‘ ‘I and 1251 respectively, and injected simultaneously. The half-lives and fractional catabolic rates of peak 1 and peak 2 in the two normal subjects were almost identical. To determine whether one peak might be a metabolic product of the other, plasma or fibrinogen samples purified from plasma obtained 2 and 6 days after infusion of the radiolabeled proteins were chromatographed on DEAE-cellulose. 1311 radioactivity eluted only in peak 1 and 125 radioactivity eluted exclusively in peak 2. These studies demonstrate that the difference in concentration between peak 1 and peak 2 is not due to a difference in their catabolic rates and that there is no metabolic interconversion between these two peaks. Our data, together with recent evidence, suggest that the y/ y’ heterogeneity originates from a postsynthetic modification of the fibrinogen molecule prior to its secretion into the peripheral circulation.