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Fibrinogen Non‐Inherited Heterogeneity and Its Relationship to Function in Health and Disease
Author(s) -
HENSCHENEDMAN AGNES H.
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03546.x
Subject(s) - proteolysis , asparagine , deamidation , chemistry , biochemistry , glycosylation , glutamine , fibrinogen , tyrosine , amino acid , thrombin , platelet , biology , enzyme , immunology
A bstract : In healthy individuals fibrinogen occurs in more than one million non‐identical forms because of the many possible combinations of biosynthetically or postbiosynthetically modified or genetically polymorphic sites. The various forms may show considerable differences in their functional properties. Normal variant sites are due to alternative splicing, modification of certain amino acid residues, and proteolysis. Both the Aα and the γ chain occur in two splice forms, and it is known that only the shorter γ chain can interact with platelets, but the longer may bind thrombin and factor XIII. Many types of posttranslationally modified amino acid residues are present in fibrinogen. The Aα chain is partially phosphorylated at two sites, possibly leading to protection against proteolysis. The Bβ chain is N‐glycosylated and partially proline hydroxylated, each at one site. The γ chain is N‐glycosylated at one site and the longer splice form doubly tyrosine‐sulfated. The glycosylations are believed to protect against polymerization and proteolysis. All three chains are partially oxidized at methionine residues and deamidated at asparagine and glutamine residues. The Aα and γ chain are partially carboxy‐terminally degraded by proteolysis, the shorter forms causing a decrease in polymerization, crosslinking, and clot stability. Abnormal variants occur in patients with diabetes mellitus, in the form of glycated lysine residues; in patients with certain types of cancer, in the form of crosslinked degradation products; in patients with certain types of autoimmune disease, in the form of complexes with antibodies; in cigarette smokers; and in individuals treated with acetylsalicylic acid, in the form of acetylated lysine residues.