prothrombin

Blood coagulation factor

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Blood coagulation factor one of. It exists in plasma, also called factor II. yes thrombin Of Predecessor substance The content in plasma is 10-15 mg/ Deciliter , molecular weight 68000 glycoprotein 。 Sugar content accounts for about 11%, including Galactose 、 mannose 、 Fucose 、 amino Hexose sialic acid 。 genetic Prothrombin（ Coagulation factor II) Deficiency is the rarest heredity Hemorrhagic disease One can divide prothrombin deficiency into two categories: ① Hypoprothrombinemia (Type I deficiency) antigen It is characterized by simultaneous reduction of activity; ② Abnormal prothrombin (type II deficiency), characterized by normal antigen level or reduced normal low limit prothrombin activity.

Chinese name: prothrombin
Foreign name: prothrombin, F Ⅱ^[3]

Exists in: In plasma
Concept: The predecessor of thrombin

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one form
two effect
three Activity

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form

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Prothrombin is distributed in α 2- Globulin part, Isoelectric point Is pH4.2. It is contained in Cohn zone Ⅲ/2. can 67% Saturated ammonium sulphate Salting out. available BaSO4 、 MgSO4 adsorbent. The half-life in the body is 23-36 hours. It's in Coagulation process Most of them can be consumed, and those remaining in serum are less than 15%. Prothrombin is generated from liver , generated with vitamin K Participation.

prothrombin

Prothrombin is one of the vitamin K dependent factors synthesized by the liver (other factors are Ⅶ, Ⅸ, Ⅹ Protein C 、 Protein S And bone carboxyl glutamic acid protein ）。 Including 579 Amino acid residue Single chain of glycoprotein , molecular weight 72000. From the N-terminal, there is one Gla region (1-40), two ring regions (41-271) and one catalytic region (271-579). Gla area contains 10 r- carboxyl Glutamate residues, whose main function is to bind phospholipids by binding calcium ions. The ring region is involved in its interaction with the substrate and cofactors. Ring region 2 can bind to F Ⅴ a and contain the action site of F Ⅹ a histidine 205 ～ arginine 220. The catalytic area includes the active area and Serine protease Zone. stay calcium ion Prothrombin is activated by F Xa with the participation of F Ⅴ a, F Ⅴ a and phospholipids. Prothrombin alone Arginine 320 places cracked to produce one Intermediate product And further lysed at arginine 284 and arginine 155 to generate thrombin, prothrombin fragment 1 and prothrombin fragment 2, respectively. Thrombin consists of A chain and B chain linked by disulfide bond, containing 308 Amino acid residue , molecular weight 36000. The A-chain contains 49 amino acid residues, also known as light chain , its function is unknown. The B chain contains 259 amino acid residues, and the weighed chain is the site where the enzyme activity is located serine protease That is, in the B chain. The serine protease region has protease activity and contains the part that recognizes and lyses the substrate. The enzyme active amino acid is histidine 363, Aspartate 419 and serine 525. The arginine 382 arginine 393 fragment in this region is called anion Junction site , is prothrombin and Fibrinogen ， Thrombomodulin and hirudin Position of action.

prothrombin

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prothrombin

Prothrombin in Coagulation mechanism Plays a central role in. In activated factor V and by platelet Or the phospholipid surface provided by other cells, the activated factor X activates to form thrombin. Thrombin is a Proteolytic enzyme , for multiple Coagulation factor have Hydrolysis 。 Thrombin Fibrinogen Into fibrin 。 In addition, it also has: ⑴ Induction platelet aggregation ；⑵ Activate factor XIII; ⑶ send Fibrinolytic enzyme The protoplast is converted into plasmin, thus activating Fibrinolytic system ；⑷ Activates the fibrinolytic inhibitor activated by thrombin; ⑸ Activation factor Ⅴ, Ⅷ, XI, generate more thrombin; (6) Activating protein C system; (7) stimulate wound healing 。 Therefore, prothrombin deficiency or Structural anomaly Causes thrombin to cause abnormality of coagulation mechanism.

Activity

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Prothrombin activity What is it?^[1] ？ Prothrombin is Blood coagulation factor One, prothrombin is synthesized by the liver vitamin K One of the dependent factors, so Liver function test It is necessary to detect the activity of prothrombin in. Prothrombin activity (PTA) is used to judge the severity of hepatocyte necrosis and prognosis Sensitive indicators.

prothrombin time The normal value is 12-14 seconds, and its normal activity is 75% ～ 100% 。 Prothrombin time mainly reflects Extrinsic coagulation Whether it is normal.

Clinical significance

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Coagulation factor Most of them are in Hepatocyte Internal synthesis. When the liver function is normal, the content and activity of coagulation factors are in the normal range. When the liver parenchyma is damaged, the content and activity of coagulation factors can be reduced to varying degrees, often resulting in bleeding Congestion And other clinical manifestations, such as Gingival bleeding 、 Epistaxis , cyan and purple stains, etc.

When Acute hepatitis The decrease of prothrombin activity was not obvious. If it is severe Hepatitis B patients , or cirrhosis In patients with chronic hepatitis B, when testing the activity of prothrombin, it will be found that the activity of prothrombin will be significantly reduced, which indicates that the condition has worsened sharply and the liver cells have been severely damaged. The judgment basis is: the activity of prothrombin is less than 40%, which is Hepatocyte necrosis The positive boundary of.

activation

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Coagulation Zymogen (II, prothrombin) is 582 Amino acid residue The proenzyme of N? Was cut by factor Xa at Arg Thr and Arg Ile, and N? 274 amino acids at the end Residue The remaining 308 amino acid residues are divided into A and B Peptide chain , by a Disulfide bond Connected, that is thrombin (thrombin)。 Factor Va None enzymatic activity However, it can increase the activity of Xa by 350 times and accelerate the production of thrombin. phospholipid Colloidal particles are connected with enzyme (Xa) and substrate (prothrombin) by Ca++as a bridge. Because of the N? The end contains 10 γ? carboxyl glutamate Residues. Adjacent carboxyl groups can form complexes with Ca++. On the other hand, Ca++can also phosphoric acid Xa and Va contact with prothrombin, so Xa hydrolyzes prothrombin to prothrombin and factors VII, XI and X are synthesized by liver, and vitamin K is required as Cofactor 。 Generated without Vitk Abnormal prothrombin , only 1?% of normal activity. Research shows that Vitk is involved in prothrombin gamma? Formation of carboxyl glutamic acid. The mechanism of Vitk's participation in carboxylation is as follows: hydroquinone Type Vitk robs γ? A proton on C, making γ - C anion , and combined with CO2. 2，3? Epoxy Vitk Enzyme catalysis Inferior quilt Lipoic acid Restored reuse So Vitk is here Carboxylation reaction Medium rise coenzyme Role of.

Prothrombin gene is located in the Chromosome 11 , 21 kb long, 14 genes Exon And 13 Intron , which mRNA It is 2kb and 622 amino acid Peptide chain of, wherein Precursor peptide 43 amino acids Secretory process Medium cracking. Although normal prothrombin Nucleotide sequence And amino acid sequence has been clarified, but its Gene variation The research of is not as deep as that of F Ⅷ and F Ⅸ. Abnormal prothrombin calcium ion Defects in the junction site, defects in the cleavage of F ⅹ a and defects in the production of thrombin activity. Similar to F Ⅷ and F Ⅸ, mutations in the CpG dinucleotide sequence are more common. The substitution of a single amino acid can occur at the site that affects the cleavage of F ⅹ a, the site of enzyme activity, and the site of calcium binding.

time

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prothrombin time^[2] , PT for short, refers to adding excessive tissue factor （ Rabbit brain Exudate ）After that, prothrombin is converted into thrombin, leading to the time required for plasma coagulation. The normal value is 12-14 seconds.

prothrombin time In general, the significance of determination is to reflect the liver synthesis function, reserve function, disease severity and prognosis. The disease type can be roughly judged according to whether the normal value is high or low.

Significance of prothrombin time measurement I: diagnosis hepatopathy Severity of. The liver is the main place for the formation of coagulation factors liver function When damaged, coagulation factors cannot be synthesized normally, which leads to high prothrombin time and prolongation.

Significance of prothrombin time measurement II: low prothrombin time is found in women Oral contraceptives , thromboembolic disease and Hypercoagulability Status, etc.

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Hereditary prothrombin deficiency It is a rare coagulation factor genetic Defects. Normal protein synthesis The person caused by reduction is also called Hypoprothrombinemia , and Abnormal protein The person who causes the synthesis of plasma molecules is called abnormal prothrombinemia. the former Cross reactive substance Negative, the latter is positive. At present, there are more cases of abnormal prothrombin than of low prothrombin.

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