alexa Fibrinogen non-inherited heterogeneity and its relationship to function in health and disease.


Journal of Blood Disorders & Transfusion

Author(s): HenschenEdman AH

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Abstract 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 A alpha and the gamma chain occur in two splice forms, and it is known that only the shorter gamma 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 A alpha chain is partially phosphorylated at two sites, possibly leading to protection against proteolysis. The B beta chain is N-glycosylated and partially proline hydroxylated, each at one site. The gamma 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 A alpha and gamma 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.
This article was published in Ann N Y Acad Sci and referenced in Journal of Blood Disorders & Transfusion

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