PTGS1

  • OMIM: 176 805
  • UniProt: P23219
  • MGI: 97797
  • CAS Number: 9055-65-6

The prostaglandin synthase -1 or cyclooxygenase-1 (abbreviated to COX-1 ) is an enzyme which oxidizes arachidonic acid to prostaglandin H2 in two steps. COX-1 is therefore essential for the production of prostaglandin E2, which regulates the production of gastric acid, anywhere in the body controlled inflammatory reactions and for the production of thromboxane A2 in platelets, and thus the aggregation events in coagulation, as well as the vasoconstriction is responsible. In contrast to COX-2 COX-1 is present in all tissues and, therefore, its inhibition also relates to the entire body. Both are cyclooxygenases, which in turn belong to the large family of pathogen - inducible oxygenase ( PIOXs ).

For the inhibition of the enzyme are only non-specific NSAIDs that inhibit cyclooxygenase, all, available, such as acetylsalicylic acid. Aspirin can also low-dose COX -1 in lymphocytes block without damaging example the stomach. An inhibition of the inflammatory signaling pathways without side effects throughout the body is otherwise only possible by means of specific COX-2 inhibition.

Deposits in the organism

Cyclooxygenases are inside the endoplasmic reticulum, localized within the nuclear envelope and in the Golgi, and adhere the inner faces of the membranes of the cell compartments at.

COX -1 is inter alia in the following cells and organs:

  • In coagulation- inducing platelet COX-1 is exclusively ago.
  • COX -1 comes in endothelial cells of normal blood vessels before ( while COX -2 in the endothelial cells of proliferating blood vessels, inflamed tissue, and occurs in atherosclerotic lesions).
  • In the renal cortex, especially in the renal medulla is COX- 1 before. Where especially prostaglandin E2 and prostacyclin is formed, which increases especially the renal blood flow, and thus the glomerular filtration rate. COX-1 inhibiting NSAIDs may therefore in certain underlying diseases (heart failure, liver cirrhosis, renal failure) or in cases of overdose have harmful side effects on kidney function.
  • COX -1 is in the whole brain, but especially in the frontal lobe; it is believed that it is involved in the in complex integrative functions between autonomic nervous system and sensors.

Biosynthesis and Structure

Cyclooxygenase -1 is encoded on chromosome 9q32 - q33.3. It is ( in contrast to the gene of cyclooxygenase -2) to a large gene ( > 28 kb) with eleven exons, whose transcription is ubiquitous and probably little regulated. The 4,982 bases long mRNA is converted by translational and post-translational modification, which consists of 576 amino acids enzyme. In a formed from the same gene isoform (COX -3) missing 40 amino acids.

Probably ahead of time, in which the vertebrates have evolved, their development path has separated by gene duplication of the cyclooxygenase -2 and went their own evolutionary path. General aspects structure of COX-1 are described in cyclooxygenases.

Biological Function

Catalyzed reaction

2 O2 AH2 → → A H2O

Other functions

COX- 1 appears to have an influence on the formation of new blood vessels; This was discovered at cancer cells in the laboratory.

Pharmacology

  • Because in an inhibition of cyclooxygenase more arachidonic acid is the lipoxygenase pathway are available, resulting in the formation of leukotrienes has the consequence that are anti- reinforcing and anaphylaxieverstärkend, inhibitors of cyclooxygenase can trigger an asthma attack.
  • Acetylsalicylic acid (aspirin ) leads to a transacetylation at serine in position 530 in the active site of cyclooxygenase, which makes the enzyme inoperative until it is re- formed. Cyclooxygenase -1 is this 10-100 times more sensitive than cyclooxygenase -2.
  • Competitively acting NSAIDs compete in Cyclooxygenasezentrum for the binding site for arachidonic acid. Ibuprofen binds this very fast and is also washed out quickly, diclofenac or indomethacin have a trägeres binding behavior.

History

From 1972, it was speculated that there were more than a cyclooxygenase. 1988 genome and the primary protein structure of the human cyclooxygenase-1 was sequenced. 1994, tertiary and quaternary structure was known. Since then, the essential similarities and differences in structure, origin, occurrence, function and regulation of the two cyclooxygenases be investigated and cleared up more and more accurate.

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