Prothrombin

Seegers, Walter H.

doi:10.4159/harvard.9780674420403

Cited by 88 publications

(50 citation statements)

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“…It may be that: a) Factor VII and its activated form may not be inactivated or catabolized by the liver; b) elaboration of Factor VII activity is not directly dependent on protein synthesis (32) ; and c) since Factor VII apparently is involved only in the extrinsic coagulation system, it requires tissue thromboplastin for activation and utilization. It is possible that the mild continuous coagulation often observed in the perfusion system does not involve tissue thromboplastin.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of clotting factors by the isolated perfused rat liver.

Olson¹,

Miller²,

Troup³

1966

J. Clin. Invest.

102

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The liver has been proposed as a site of synthesis of blood-clotting factors, in part because of the demonstrated dominant role of the liver in synthesis of all plasma protein fractions except the y-globulins (1, 2). In addition, observations after hepatectomy (3, 4) and hepatic injury (5, 6) and in hepatic disease (7,8) have provided a body of evidence consistent with hepatic synthesis of fibrinogen, prothrombin, and Factors V, VII, IX, and X. This evidence, however, has not been considered definitive, mainly because it is based on indirect observations in vivo in humans and in animals suffering from variable, often profound, metabolic abnormalities induced by hepatic dysfunction or extirpation.This report describes the use of the isolated perfused rat liver in a more direct experimental evaluation of the role of the liver in the production of blood-clotting factors. The use of the isolated perfused liver was encouraged by Lupton's observations of shortened prothrombin time during perfusions of 3 to 4 hours (9), and by Pool and Robinson's studies of changes in clotting factor activity during in vitro incubation of rat liver slices (10). Presented here is not only more detailed direct evidence of hepatic synthesis of prothrombin and Factor VII, but also the first direct evidence for hepatic synthesis of Factors V and X.

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Section: Discussionmentioning

confidence: 99%

Synthesis of clotting factors by the isolated perfused rat liver.

Olson¹,

Miller²,

Troup³

1966

J. Clin. Invest.

102

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“…Estimating the amount of thrombin necessary to produce the maximal effect on phospholipid synthesis from the specific activity of the most highly purified thrombin preparations (60,000-70,000 U/mg tyrosine) (14) suggests that thrombin is about 50-fold more effective than trypsin in stimulating PS synthesis on a molar basis.…”

Section: Methodsmentioning

confidence: 99%

Lipid metabolism in human platelets

Lewis¹,

Majerus²

1969

J. Clin. Invest.

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A B S T R A C T Washed human platelets were incubated with radioactive glycerol; the platelets were able to synthesize de novo the major phosphoglycerides including phosphatidic acid, phosphatidylinositol, phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl serine. The specific activities of the phosphoglycerides obtained after glycerol incorporation indicate that phosphatidic acid, phosphatidylinositol, and phosphatidyl choline are metabolically active relative to phosphatidyl ethanolamine and that formation of phosphatidyl serine occurs to a much more limited extent. When platelets were incubated with bovine thrombin, 1 U/ml, the pattern of glycerol incorporation into phospholipid was changed. There was a 3-fold decrease in the total incorporation into lipid in 30 min with a relative 5-fold decreased incorporation into phosphatidyl choline and phosphatidyl ethanolamine and a 5-fold increased incorporation into phosphatidyl serine. The increased incorporation into phosphatidyl serine was maximal within the first 2 min but was transient, since within 20 minutes, the rate returned to that seen in platelets incubated with glycerol alone. Purified human thrombin also produced this same effect on phospholipid synthesis in platelets. Trypsin produced effects on phosphoglyceride formation similar to those seen with thrombin, and the trypsin-induced effect was inhibited by prior imcubation of trypsin with soybean trypsin inhibitor, suggesting that proteolysis may be required for the observed effects on phospholipid synthesis.

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“…Platelets are anucleate circulating particles, with a diameter of [2][3][4] Mum in man, which function in hemostasis. These "cells" are metabolically active and catalyze the formation of fatty acids, phospholipids, glycogen, and even protein (1).…”

mentioning

confidence: 99%

A Thrombin-Sensitive Protein of Human Platelet Membranes

Baenziger

Brodie

Majerus

1971

Proc. Natl. Acad. Sci. U.S.A.

323

201

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The action of thrombin on intact human platelets has been studied with the aid of polyacrylamide gel electrophoresis in sodium dodecylsulfate. A single major membrane protein band with a molecular weight of 190,000 disappears after thrombin treatment, while a new membrane protein with a molecular weight of 107,000 appears. This may represent hydrolysis of the thrombinsensitive protein. When platelets are disrupted or when the thrombin-sensitive protein is solubilized from membranes prior to thrombin treatment, no hydrolysis occurs. The effect of thrombin on the platelet membrane protein is complete within 2 min which suggests that hydrolysis of this membrane protein may trigger the physiological effects of thrombin on platelets.Platelets are anucleate circulating particles, with a diameter of 2-4 Mum in man, which function in hemostasis. These "cells" are metabolically active and catalyze the formation of fatty acids, phospholipids, glycogen, and even protein (1). Both glycolytic and Krebs cycle oxidative pathways are active in these cells.Blood platelets are rapidly converted from free floating cells to an aggregated mass of intact platelets during the process of hemostasis or of thrombus formation. This obvious change in the platelet surface is accompanied by a variety of morphological and biochemical changes which have been termed "viscous metamorphosis" (1). The most potent agent known to induce this process is the proteolytic enzyme thrombin, which is generated from reactions of the coagulation pathway. Characterization of the role of thrombin in producing viscous metamorphosis is integral to understanding thrombus formation and may also provide some insight into the membrane specification of cell-cell interactions.Previous work done in our laboratory (2) has shown that thrombin causes a 7-fold increase in the rate of incorporation of glycerol into phosphatidyl serine in the platelet membrane. This burst in the rate of lipid synthesis is maximal within 2 min of the addition of thrombin and such synthesis returns to the pre-thrombin rate by 20 min. Studies of the mechanism of this thrombin effect indicate that proteolysis is involved, since the effect can be mimicked by trypsin and inhibited by prior incubation of trypsin with soybean trypsin inhibitor. Human platelets, collected and isolated as described previously (2), were washed twice in a pH 6.5 isotonic buffer containing 0.113 M NaCl, 0.0043 M K2HPO4, 0.0043 M\I Na2HPO4, 0.0244 M NaH2PO4, and 1 mg/ml glucose. After washing, l)latlets were resuspended in either 0.154 M NaCl-0.154 A Tris HCl (pH 7.4) 9:1 with 1 mg/ml glucose, or in a pH 7.5 buffer containing 0.109 M NaCl, 0.043 M K2HP04, 0.0106 M Na2HPO4, 0.0083 MI NaH2PO4, and 1 mg/ml glucose.Platelets were incubated at 370C at 1-2 X 109 cells/ml in resuspension buffer with or without 1 U/ml thrombin and 2.5 mM CaCl2. The cells were disrupted by no-clearance-pestle homogenization (5), glycerol loading, and hypotonic lysis (6) Samples were solubilized in 1-3%o SDS-1%o 0-mercaptoethanol -0.1 AM so...

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Prothrombin

Cited by 88 publications

References 0 publications

Synthesis of clotting factors by the isolated perfused rat liver.

Synthesis of clotting factors by the isolated perfused rat liver.

Lipid metabolism in human platelets

A Thrombin-Sensitive Protein of Human Platelet Membranes

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