KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | Michaelis-Menten steady-state kinetics, kinetic isotope effect of 5-LOX, detailed overview. The reaction of 5-LOX with unlabeled arachidonate generates products from hydrogen abstraction at C7 (95% 5-HETE) with minor products derived from abstraction at C10 (5% 8-HETE). With 7,7-d2-arachidonate the selectivity remains skewed towards C7 hydrogen abstraction (59%) compared to C10 hydrogen abstraction products (41% 8-HETE), but the selectivity is significantly reduced compared to unlabeled arachidonate. 5-LOX exhibits isotope sensitive branching, shift in regiospecificity induced by deuterium-labeling. Dependence of the steady-state velocity on arachidonate concentration follows Michaelis-Menten kinetics up to 0.04-0.05 mM, effects of temperature and viscosity | Homo sapiens | |
0.0093 | - |
7,7-d2-arachidonate | pH 7.5, 25°C, HPLC analysis, 8-HETE formation | Homo sapiens | |
0.01144 | - |
7,7-d2-arachidonate | pH 7.5, 25°C, UV-Vis spectrophotometric analysis | Homo sapiens | |
0.0223 | - |
arachidonate | pH 7.5, 25°C, UV-Vis spectrophotometric analysis | Homo sapiens | |
0.0285 | - |
arachidonate | pH 7.5, 25°C, HPLC analysis, 8-HETE formation | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe | required for catalysis, oxidizes Fe2+ to Fe3+ | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | Homo sapiens | - |
(5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P09917 | - |
- |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
arachidonate + O2 = (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyicosa-6,8,11,14-tetraenoate | a non-classical reaction mechanism | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,7-d2-arachidonate + O2 | analysis of the product distribution reveals that 5-LOX displays a reversal of selectivity to bypass abstracting the deuterium atom from C7 | Homo sapiens | 7-d-(5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? | |
arachidonate + O2 | - |
Homo sapiens | (5S,6S,7E,9E,11Z,14Z)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O | - |
? | |
additional information | 5-LOX catalyzes a 2-step reaction where arachidonic acid (AA) is oxygenated, resulting in formation of 5(S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HPETE), with subsequent formation of leukotriene A4 (LTA4). Active site structure and binding of substrate arachidonate involving residues F421, F177, Q363, L414 and L368 during the reaction, model, overview | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
5-lipoxygenase | - |
Homo sapiens |
5-LOX | - |
Homo sapiens |
Temperature Minimum [°C] | Temperature Maximum [°C] | Comment | Organism |
---|---|---|---|
additional information | - |
analysis of temperature dependence of kinetics at 4-35°C with labeled and unlabeled substrates | Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.001 | - |
7,7-d2-arachidonate | pH 7.5, 25°C, HPLC analysis, 8-HETE formation | Homo sapiens | |
0.004 | - |
arachidonate | pH 7.5, 25°C, HPLC analysis, 8-HETE formation | Homo sapiens | |
0.01 | - |
7,7-d2-arachidonate | pH 7.5, 25°C, UVVis spectrophotometric analysis | Homo sapiens | |
0.06 | - |
arachidonate | pH 7.5, 25°C, UVVis spectrophotometric analysis | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediator. Role of active site residues F421, Q363 and L368 in regulating the donor-acceptor distances, thus affecting H-transfer as well as regiospecificity of the enzyme reaction, the H-abstraction is the rate limiting step for 5-LOX and the observed KIE of 5-LOX is masked by a change in regioselectivity | Homo sapiens |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.108 | - |
7,7-d2-arachidonate | pH 7.5, 25°C, HPLC analysis, 8-HETE formation | Homo sapiens | |
0.14 | - |
arachidonate | pH 7.5, 25°C, HPLC analysis, 8-HETE formation | Homo sapiens | |
0.87 | - |
7,7-d2-arachidonate | pH 7.5, 25°C, UV-Vis spectrophotometric analysis | Homo sapiens | |
2.69 | - |
arachidonate | pH 7.5, 25°C, UV-Vis spectrophotometric analysis | Homo sapiens |