Plasmin

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Plasmin
Properties of human protein
Mass / length primary structure 791 = 561 + 230 amino acids
Precursor Plasminogen (791  AA )
Identifier
Gene name PLG
External IDs
Enzyme classification
EC, category 3.4.21.7 ,  peptidase
MEROPS S01.233
Response type proteolytic cleavage
Substrate mainly fibrin
Products soluble fibrin components
Occurrence
Homology family PLG
Parent taxon Euteleostomi
Orthologue
human House mouse
Entrez 5340 18815
Ensemble ENSG00000122194 ENSMUSG00000059481
UniProt P00747 P20918
Refseq (mRNA) NM_000301 NM_008877
Refseq (protein) NP_000292 NP_032903
Gene locus Chr 6: 160.7 - 160.75 Mb Chr 17: 12.38 - 12.42 Mb
PubMed search 5340 18815

Plasmin is an enzyme from the peptidase group that can cleave and break down many proteins in the blood plasma . This property is particularly effective on fibrin in blood clots . The process that takes place is called fibrinolysis ( fibrin splitting ).

Plasmin is a serine proteinase that is formed from the precursor plasminogen .

history

Kenneth M. Moser (* 1929) reported in 1951 that plasmin can be used in acute deep-seated thrombophlebitis . He used the local application . In 1955, William Smyth Tillett administered it intravenously for the first time .

Eugene E. Cliffton also successfully treated thrombophlebitis with plasmin in 1956 and 1957 .

In 1967 AL Dechter found the analgesic effect of the substance with repeated intravenous administration. And AP Fletcher used it to treat tuberculous meningitis .

Plasminogen

Plasmin is synthesized in a preliminary stage as plasminogen by the liver and released into the bloodstream and can also be measured as such. Plasminogen has a biological half-life of 2.2 days. Free, active plasmin cannot be detected in normal blood, or only in very small amounts.

Plasminogen is determined from citrated blood . The normal value in the blood is:

  • Plasminogen activity 85-110%
  • Plasminogen concentration 0.2 g / l

Human plasminogen was also the first marker that, through its specific binding, can reliably differentiate between pathologically folded prion protein (PrPSc) and the normal cellular form of the protein (PrPC).

function

The main task of plasmin is to cleave fibrin . Plasmin can be called the fibrin scissors in the coagulation system. The thrombin would then be the opposite, namely the loom of fibrin coagulation.

The soluble precursor of fibrin, fibrinogen , is also broken down into fibrinogen breakdown products by plasmin. The fibrin (ogen) cleavage products for their part inhibit the fibrin crosslinking.

The specificity of plasmin towards fibrin results from the fact that plasminogen attaches to fibrin threads during coagulation and is only activated there.

Serine proteases such as plasmin have irreversible effects. This is in contrast to most other enzymes which catalyze biochemical reactions in both directions .

As a serine protease, plasmin also has the so-called catalytic triad in its amino acid sequence

Plasmin has an autocatalytic effect d. This means that it converts further molecules of plasminogen into active plasmin: the proenzyme is the substrate of the activated enzyme. 

          t-PA (Plasminogenaktivatoren)
          u-PA
            ↓
Plasminogen → Plasmin
                 ↓
          Fibrin → Fibrinspaltprodukte

In addition to its fibrinolytic activity, plasmin can cleave various other proteins :

Plasmin is also a very effective activator of monocytes.

The plasminogen / plasmin system plays an important role in the regression of the female breast after weaning.

In general, certain amounts of plasmin and plasminogen get from the blood into the milk, which is also important for the production of cheese in cow, sheep and goat milk, since the proteolytic activity of plasmin creates certain breakdown products with a specific aroma.

The effectiveness of oral plasmin as an anti-tumor agent is unproven and unlikely as plasmin is destroyed by digestion.

activation

Plasminogen is activated by the following substances:

Inactivation

It is inactivated by the following substances:

ε-aminocaproic acid, para- aminomethylbenzoic acid and tranexamic acid are among the ε-aminocarboxylic acids . These are synthetic substances that are similar to lysine. They block the lysine binding site on plasmin, which is essential for the enzymatic effect of plasmin.

A lack of plasmin can lead to thrombosis as the clot dissolution does not work properly. Arsenic blocks the production of plasmin and uses it to develop part of its chronic toxicity in the blood vessels.

variants

A shortened version of plasmin ( ocriplasmin ) is used in ophthalmology.

literature

  • David M. Waisman (Editor): Plasminogen: Structure, Activation, and Regulation . Springer US, 2003 ISBN 0-306-47699-1

Web links

Individual evidence

  1. ^ A b c Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2nd, revised and expanded edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2005, ISBN 978-3-8047-2113-5 , p. 117 .
  2. ^ Research projects at Ulm University ( Memento from May 8, 2005 in the Internet Archive ).
  3. ^ Mammary Involution, Plasminogen / Plasmin System ( Memento from January 15, 2006 in the Internet Archive ).