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Literature summary for 1.13.11.34 extracted from

  • Mittal, M.; Kumar, R.B.; Balagunaseelan, N.; Hamberg, M.; Jegerschoeld, C.; Radmark, O.; Haeggstroem, J.Z.; Rinaldo-Matthis, A.
    Kinetic investigation of human 5-lipoxygenase with arachidonic acid (2016), Bioorg. Med. Chem. Lett., 26, 3547-3551 .
    View publication on PubMed
Search for more literature for 1.13.11.34

KM Value [mM]

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

Metals/Ions Comment Organism Structure
Fe required for catalysis, oxidizes Fe2+ to Fe3+ Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens P09917
-
-

Reaction

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
a

Substrates and Products (Substrate)

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

Synonyms Comment Organism
5-lipoxygenase
-
 Homo sapiens
5-LOX
-
 Homo sapiens

Temperature Range [°C]

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 [1/s]

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, UV–Vis spectrophotometric analysis Homo sapiens
0.06
-
 arachidonate pH 7.5, 25°C, UV–Vis spectrophotometric analysis Homo sapiens

General Information

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 [mM/s]

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