Carbohydrate Composition And Catabolism Of Five Abnormal Fibrinogens

An investigation has been made of the carbohydrate composition and catabolism of five abnormal fibrinogens. These were fibrinogens, London, Manchester, Oslo II, a fetal fibrinogen isolated from pooled cord blood and a newly discovered case of hypodysfibrinogenemia which has been tentatively designated fibrinogen London II. The carbohydrate composition of fibrinogen (mol sugar/mol of fibrinogen) was studied by amino acid analysis techniques for amino sugars and methanolysis followed by GLC for neutral sugars and sialic acid. The adult variants did not differ significantly from the normal adult fibrinogen which typically contained 22 mannose, 18 galactose, 20 N-acetylglucosamine, 4 N-acetyl- galactosamine and 12 sialic acid residues. However, fetal fibrinogen was markedly different, containing 15 mannose, 21 galactose, 14 N-acetylglucosamine, 20 N-acetylgalactosamine and 20 sialic acid residues. The catabolism of the I¹²⁵- labelled fibrinogens was studied in New Zealand White rabbits. Normal fibrinogen was eliminated with a mean t1/2 of 50.2 h (n = 5, range 42-60). The mean t1/2 of fetal fibrinogen was similar 47.7 h (n = 5, range 41-70) and fibrinogens London, London II, Manchester and Oslo II had t1/2’s of 39, 42, 38 and 44 h respectively. It is concluded that (a) the increased sialic acid on fetal fibrinogen is probably due to there being more O-glycosylated serine or threonine residues and this does not alter catabolism, (b) the reduced plasma fbgen of London II is caused by impaired synthesis rather than hypercatabolism, and (c) the catabolism of fibrinogen is only minimally dependent upon the full integrity of the regions of the molecules involved in polymerisation and fibrinopeptide releasing functions.