The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms.
5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid to leukotriene A4 (LTA4). The first step consists of the oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and the second step is the dehydration of 5-HPETE to form LTA4. These events are the first committed reactions leading to the synthesis of all leukotrienes and play a critical role in controlling leukotriene production. 5-LO has evolved many complex structural features and regulatory mechanisms to allow it to fulfill this highly specialized role. The biology of 5-LO is reviewed here with an emphasis on enzymatic function, protein and gene structure, essential cofactors, and the many regulatory mechanisms controlling its expression.
Silverman
E S
ES
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Drazen
J M
JM
D000255:Adenosine Triphosphate / Q000502:physiology; D000494:Allosteric Regulation; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D004789:Enzyme Activation; D004790:Enzyme Induction; D005796:Genes; D006801:Humans; D007501:Iron / Q000502:physiology; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017572:Leukotriene A4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009154:Mutation; D009363:Neoplasm Proteins / Q000502:physiology; D009928:Organ Specificity; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D007527:Isoenzymes; D017572:Leukotriene A4; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016718:Arachidonic Acid; C025348:arachidonic acid 5-hydroperoxide; D000255:Adenosine Triphosphate; D007501:Iron; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium