The activation of coagulation factor X. Identity of cleavage sites in the alternative activation pathways and characterization of the COOH-terminal peptide.
Bovine Factor X can be activated by two alternative pathways. The first, favored at high concentrations of the complex of tissue factor and Factor VII, is initiated by the action of Factor VII on Factor X to cleave an activation peptide from the NH2 terminus of the heavy chain, to produce alpha-Xa. This is then converted autocatalytically to another form of Factor Xa, beta-Xa, by the loss of a 17-residue glycopeptide from the COOH terminus of the heavy chain, in a lipid-dependent reaction. The alternative pathway, favored at lower activator concentrations, is initiated by the action of Factor Xa on Factor X, in the presence of lipid, to release the same COOH-terminal peptide as is produced in the conversion of alpha-Xa to beta-Xa. The intermediate produced by the loss of this peptide from Factor X,I1, can be activated directly to beta-Xa by the tissue factor-Factor VII complex, with the loss of the same NH2-terminal peptide as is produced in the conversion of Factor X to alpha-Xa. The autocatalytic activation of Factor X by Factor Xa described previously occurs to a marked extent only at very low activator concentrations, and has been shown to proceed largely by the loss of the normal NH2-terminal peptide from the heavy chain of I1-Initial experiments show that neither peptide affects the rate of coagulation by either the extrinsic or intrinsic pathways. The amino acid sequences have been determined on both sides of the peptide cleavages, and it has been shown that the cleavage sites are the same, regardless of the pathway of activation. The amino acid sequence and carbohydrate composition of the COOH-terminal peptide have been determined. The carbohydrate moiety is attached via an O-glycosidic linkage at a threonine residue, and contains galactosamine but no glucosamine.
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002268:Carboxypeptidases; D002417:Cattle; D005170:Factor X / Q000378:metabolism; D005688:Galactosamine / Q000032:analysis; D005690:Galactose / Q000032:analysis; D005944:Glucosamine / Q000032:analysis; D007461:Iodoacetates; D046911:Macromolecular Substances; D008358:Mannose / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D012794:Sialic Acids / Q000032:analysis; D013381:Subtilisins; D014364:Tryptophan / Q000032:analysis
D000596:Amino Acids; D007461:Iodoacetates; D046911:Macromolecular Substances; D010446:Peptide Fragments; D012794:Sialic Acids; D005688:Galactosamine; D014364:Tryptophan; D005170:Factor X; D002268:Carboxypeptidases; D013381:Subtilisins; D005944:Glucosamine; D008358:Mannose; D005690:Galactose