Human fibrinogen heterogeneity: the COOH-terminal residues of defective A alpha chains of fibrinogen II.

Fibrinogen fraction I (340 kDa) and fraction II (305 kDa) were isolated by glycine precipitation. The subunit chains of the two fractions were separated, after reduction, by reverse-phase high performance liquid chromatography. The amino acid compositions of the B beta and tau chains of fibrinogen II were identical with those of fibrinogen I. In contrast, the A alpha chains of fibrinogen II were composed of two populations, one comprising homogeneous, intact A alpha chains and the other consisting of heterogeneous, deficient A alpha chains (A alpha' chains) of lengths varying according to the sizes of their COOH-terminal defects. The molar ratio of the A alpha to the A alpha' chains in fibrinogen II was 1.16:1. The amino acid composition and sequence analyses of the TPCK-trypsin peptides derived from the A alpha' chains revealed that the COOH-terminal residues of the A alpha' chains were mainly Asn-269, Gly-297 and Pro-309. These results indicate that the fibrinogen II molecule is asymmetrical and can be represented by the formula (A alpha) (A alpha')(B beta)2(tau)2 and that fibrinogen II cannot be a plasmin degradation product of fibrinogen I.