Heterogeneity in human prothrombin: analysis of cause
SP Bajaj, SI Rapaport, C Prodonos and WA Russell
Two fractions of human prothrombin can be isolated from single donor plasma
by the technique of heparin-agarose chromatography in (sodium) citrate
buffer, pH 7.5, as previously reported for pooled plasma. The two
fractions, designated H-II1 and H-II2, are found in a ratio of
approximately 4:1. Both forms comigrate in sodium dodecyl sulfate gel
electrophoresis; however, under nondenaturing electrophoretic conditions,
each fraction migrates as a discrete entity with a different mobility. The
larger fraction (H-II1) has a faster mobility towards the anode.
Isoelectric focusing in urea of H-II1 reveals that it has two components, a
minor component with a pl of 5.25 (H-II1a) and a major component with a pl
of 5.40 (H-II1b). H-II2 has a pl of 5.6 H- II1 and H-II2 possess the same
amino terminal residue (alanine, 0.87- 0.92 mole/mole) and the same number
of gamma -carboxyglutamic acid residues (9.8-10.5). Their amino acid
composition is indistinguishable. However, the two fractions of prothrombin
differ in their content of neutral sugar and of sialic acid residues.
Removal of sialic acid with neuraminidase abolishes the electrophoretic
heterogeneity. Thus, the charge heterogneity of the three variants of
prothrombin found in normal human plasma appears to result exclusively from
differences in the number of sialic acid residues attached to the protein
moiety of the molecule.
Volume 58,
Issue 5,
pp. 886-891,
11/01/1981
Copyright © 1981 by The American Society of Hematology
