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| CAS No.: | 9002-04-4 |
|---|---|
| Name: | Thrombin |
| Molecular Structure: | |
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| Formula: | NULL |
| Molecular Weight: | 0 |
| Synonyms: | Blood-coagulationfactor II, activated; Blood-coagulation factor IIa; E.C. 3.4.21.5; E.C.3.4.4.13; Factor IIa; Thrombase; Thrombin JMI; Thrombin-C; Thrombinar;Thrombofort; Thrombostat; Topical; Tropostasin |
| EINECS: | 232-648-7 |
| Melting Point: | 47.7 °C |
| Appearance: | Powder |
| Hazard Symbols: |
 
|
| Risk Codes: | 36/37/38-42 |
| Safety: | A poison by intravenous route. Low toxicity by skin contact. Mutation data reported. When heated to decomposition it emits acrid smoke and irritating vapors. |
| PSA: | 0.00000 |
| LogP: | 0.00000 |
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Chemistry
Product Name: Thrombin
Synonyms of Thrombin (CAS NO.9002-04-4): Thrombin, bovine ; Bovine thrombin ; Coagulation factor iia ; Factor iia ; Thrombin from bovine plasma ; Thrombin from human plasma
Solubility in H2O: 1 mL/vial clear to slightly hazy, colorless solution
Storage temp: -20 °C
Form: powder
Color: white
Merck: 13,9461
History
After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872.
Uses
Due to its high proteolytic specificity, Thrombin (CAS NO.9002-04-4) is a valuable biochemical tool.The thrombin cleavage site (Leu-Val-Pro-Arg-Gly-Ser) is commonly included in linker regions of recombinant fusion protein constructs. Following purification of the fusion protein, thrombin can be used to selectively cleave between the Arginine and Glycine residues of the cleavage site, effectively removing the purification tag from the protein of interest with a high degree of specificity.
Thrombin converts fibrinogen to an active form that assembles into fibrin. Thrombin also activates factor XI, factor V, and factor VIII. This positive feedback accelerates the production of thrombin.
Production
Thrombin (CAS NO.9002-04-4) is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly enhanced by binding to activated Factor V (Va), termed the prothrombinase complex. Prothrombin is produced in the liver and is post-translationally modified in a vitamin K-dependent reaction that converts ten glutamic acids on prothrombin to gamma-carboxyglutamic acid (Gla). In the presence of calcium, the Gla residues promote the binding of prothrombin to phospholipid bilayers (see the picture). Deficiency of vitamin K or administration of the anticoagulant warfarin inhibits the production of gamma-carboxyglutamic acid residues, slowing the activation of the coagulation cascade.
In human adults the normal blood level of antithrombin activity has been measured to be around 1.1 units /ml. Newborn levels of thrombin steadily increase after birth to reach normal adult levels, from a level of around 0.5 units/ml 1 day after birth, to a level of around 0.9 units/ml after 6 months of life.
Toxicity Data With Reference
| Organism | Test Type | Route | Reported Dose (Normalized Dose) | Effect | Source |
|---|---|---|---|---|---|
| mouse | LD50 | intraperitoneal | > 50mL/kg (50mL/kg) | BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION | Oyo Yakuri. Pharmacometrics. Vol. 28, Pg. 329, 1984. |
| mouse | LD50 | intravenous | 7771ug/kg (7.771mg/kg) | BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX) KIDNEY, URETER, AND BLADDER: OTHER CHANGES LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES | Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 16, Pg. 669, 1988. |
| mouse | LD50 | skin | > 3gm/kg (3000mg/kg) | BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY) LUNGS, THORAX, OR RESPIRATION: DYSPNEA SKIN AND APPENDAGES (SKIN): HAIR: OTHER | Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 1, Pg. 272, 1973. |
| mouse | LD50 | subcutaneous | > 50mL/kg (50mL/kg) | Oyo Yakuri. Pharmacometrics. Vol. 28, Pg. 329, 1984. | |
| rat | LD50 | intraperitoneal | > 40mL/kg (40mL/kg) | BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION | Oyo Yakuri. Pharmacometrics. Vol. 28, Pg. 329, 1984. |
| rat | LD50 | subcutaneous | > 40mL/kg (40mL/kg) | Oyo Yakuri. Pharmacometrics. Vol. 28, Pg. 329, 1984. |
Consensus Reports
Reported in EPA TSCA Inventory.
Safety Profile
A poison by intravenous route. Low toxicity by skin contact. Mutation data reported. When heated to decomposition it emits acrid smoke and irritating vapors.Safety information of Thrombin (CAS NO.9002-04-4):
Hazard Codes 
Xn,
B
Risk Statements
36/37/38 Irritating to eyes, respiratory system and skin
42 May cause sensitization by inhalation
Safety Statements
22 Do not breathe dust
24/25 Avoid contact with skin and eyes
36/37 Wear suitable protective clothing and gloves
WGK Germany 2
RTECS XO8950000
HS Code 30021099
Specification
Thrombin also commonly called pro-thrombin is a coagulation protein in the blood stream that has many effects in the coagulation cascade. It is a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.
The Thrombin (prothrombin) gene is located on the eleventh chromosome (11p11-q12). The molecular weight of prothrombin is approximately 72000 gmol-1. The catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36000 gmol-1.
There are an estimated 30 people in the world that have been diagnosed with the congenital form of Factor II deficiency,which should not be confused with a mutation of prothrombin. The prothrombin gene mutation is called Factor II mutation. Factor II mutation is congenital. The Factor II mutated gene is not usually accompanied by other factor mutations (i.e. the most common is Factor V Leiden). The gene may be inherited heterozygous (1 pair), or much more rarely, homozygous (2 pairs), and is not related to gender or blood type. Homozygous mutations increase the risk of thrombosis more than heterozygous mutations, but the relative increased risk is not well documented. Other potential risks for thrombosis, such as oral contraceptives may be additive. The previously reported relationship of inflammatory bowel disease (i.e. Crohn's disease or Ulcerative Colitis) and prothrombin mutation or Factor V Leiden mutation have been contradicted by research.