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Biosynthesis and metabolism of leukotrienes.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Murphy, Robert C. Gijón, Miguel A. |
| Copyright Year | 2007 |
| Abstract | Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Several other proteins, including cPLA2a (cytosolic phospholipase A2a) and FLAP (5-LO-activating protein) also assemble at the perinuclear region before production of LTA4. LTC4 synthase is an integral membrane protein that is present at the nuclear envelope; however, LTA4 hydrolase remains cytosolic. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by b-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/15-oxo-prostaglandin-13-reductase that forms a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a g-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. |
| Starting Page | 035003 |
| Ending Page | 035003 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.biochemj.org/content/ppbiochemj/405/3/379.full.pdf |
| PubMed reference number | 17623009v1 |
| Volume Number | 405 |
| Issue Number | 3 |
| Journal | The Biochemical journal |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Acylglycerophosphocholine O-Acyltransferase Acyltransferase Anabolism Arachidonate 5-Lipoxygenase Arachidonic Acid Carboxyl Group Carrier Proteins Cascade Device Component Cell Nucleus Esters Gamma-glutamyl transferase Hereditary Diseases Hydrolase Immunostimulating conjugate (antigen) Integral Membrane Proteins Leukotriene A4 Leukotriene B4 Leukotriene C4 Leukotriene D4 Leukotriene E4 Leukotriene Production Leukotrienes Manuscripts Mental Retardation Metabolic Diseases Metabolic Process, Cellular Metabolite Nuclear Envelope Outer nuclear membrane Peptide Hydrolases Peptidyltransferase Phagosomes Phospholipase Preparation Protein Data Bank Surgical Flaps Tissue membrane acyl-CoA dehydrogenase arachidonic acid 5-hydroperoxide cell transformation diene funding grant leukotriene biosynthetic process leukotriene metabolic process lysophosphatidic acid oxidation physiological aspects |
| Content Type | Text |
| Resource Type | Article |
