Lysine as amine donor in fibrin crosslinking

Lóránd, L.; Ong, Hwei Ling; Lipiński, Bogusław; Rule, N. G.; Downey, Jeanne E.; Jacobsen, Ann-Christin

doi:10.1016/0006-291x(66)90501-8

Cited by 69 publications

(19 citation statements)

References 15 publications

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“…As no difference was found between the amount of HMF and the amount of furosine formed by the hydrolysis of fibrin(ogen), we assume that lysine is the site of glycosylation in fibrinogen. As was shown by Lorand et al [11], lysine is the amino donor in fibrin cross-linking. They demonstrated that 2.7-4.5 mol lysine/mol fibrin are involved in this process.…”

Section: Discussionmentioning

confidence: 72%

Glycosylation of human fibrinogen in vivo

et al. 1985

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Summary.Fibrinogen was purified from plasma from 22 nondiabetic and 26 poorly controlled Type I (insulin-dependent) diabetic subjects. In non-diabetic subjects, 0.95+0.17mol glucose was bound per mol fibrinogen, whereas in the diabetic subjects 1.33 + 0.21 mol glucose was bound per tool fibrinogen (mean + SD, p < 0.001). Comparison of the amount of bound glucose, when estimated by two different methods, suggested that lysine is the site of glycosylation. It is currently unknown whether this increased glycosylation of fibrinogen alters its function.Key words: Fibrinogen, glycosylation, Type I diabetes.Glucose has been shown to bind non-enzymatically and irreversibly to all types of protein through Schiff-base formation and Amadori re-arrangement to a ketoamine [1]. This glycosylation appears to be dependent on the duration of exposure and glucose concentration in the surrounding medium. Glycosylation occurs either on the amino terminal end of the protein, as with haemoglobin [2], or on the free amino group of lysine. Because of this glycosylation, the tertiairy or quaternary structure, function and/or degradation of the protein molecule may be altered, as has been demonstrated with glycosylated haemoglobin (HbA0 Fibrinogen is a protein with a half-life of 3-4 days, which occupies a central position in blood clotting. It is known that the e-amino groups of lysine in the fibrinogen molecule play an important role in cross-linking fibrin monomers and in fibrinolysis. We have therefore investigated whether glycosylation of fibrinogen is increased in the blood of diabetic patients. Subjects and methods SubjectsTwenty-two healthy volunteers (aged 21-59 years, mean 33 years; mean blood glucose level at the time of sampling, 5.1 _+ 1.0 mmol/1) and 26 Type 1 (insulin-dependent) diabetic patients (aged 19-57 years, mean 36 years; taking no medication other than insulin) participated in the study. MethodsBlood was collected in 3.2% sodium citrate (1 : 10, wt/vol) for purification of fibrinogen and estimation of glycosylation. After centrifugation at 5000 g for 20 min, plasma was either processed immediately or stored at -26~ Blood was also taken for estimation of glucose and HbAv HbA1 was estimated by the microcolumn method ([solab In-

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Section: Discussionmentioning

confidence: 72%

Glycosylation of human fibrinogen in vivo

et al. 1985

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“…The thioester intermediate is highly reactive, and there is rapid formation of the isopeptide bond (Figure 4). 41,42 If there are no primary amines available in the active-site pocket, the enzymesubstrate complex will react with water, releasing the enzyme and converting glutamine to glutamic acid.…”

Section: Catalytic Mechanismmentioning

confidence: 99%

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Ariëns

Lai

Weisel

et al. 2002

Blood

327

272

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Factor XIII and fibrinogen are unusual among clotting factors in that neither is a serine protease. Fibrin is the main protein constituent of the blood clot, which is stabilized by factor XIIIa through an amide or isopeptide bond that ligates adjacent fibrin monomers. Many of the structural and functional features of factor XIII and fibrin(ogen) have been elucidated by protein and gene analysis, site-directed mutagenesis, and x-ray crystallography. However, some of the molecular aspects involved in the complex processes of insoluble fibrin formation in vivo and in vitro remain unresolved. The findings of a relationship between fibrinogen, factor XIII, and cardiovascular or other thrombotic disorders have focused much attention on these 2 proteins. Of particular interest are associations between common variations in the genes of factor XIII and altered risk profiles for thrombosis. Although there is much debate regarding these observations, the implications for our understanding of clot formation and therapeutic intervention may be of major importance. In this review, we have summarized recent findings on the structure and function of factor XIII. This is followed by a review of the effects of genetic polymorphisms on protein structure/function and their relationship to disease. (Blood. 2002;100:743-754)

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“…The covalent cross-linking of fibrin units occurs through an amide exchange reaction (transamidation) between select glutamine and lysine residues of neighboring protein molecules [27][28][29][30][31] (Figure 3a). As a result, a few strategically located N ⑀ (␥-glutamyl)lysine side chain bridges are formed.…”

Section: The Urea-insoluble Clotmentioning

confidence: 99%

Sol Sherry Lecture in Thrombosis

Lóránd

2000

ATVB

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Lysine as amine donor in fibrin crosslinking

Cited by 69 publications

References 15 publications

Glycosylation of human fibrinogen in vivo

Glycosylation of human fibrinogen in vivo

Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms

Sol Sherry Lecture in Thrombosis

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