Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that catalyzes the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) to the dihydroxy acid leukotriene B4 (LTB4) (Radmark et al. 1984, McGee & Fitzpatrick 1985).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H can also catalyse the hydrolysis of 5S,6S-epoxy-18(R)-HEPE to the 18(R) stereoisomer of resolvin E1 (18(R)-RvE1) (Oh et al. 2011). The E-resolvins are antiinflammatory, pro-resolving, and non-phlogistic (that is, they mediate the clearance of leukocytes without eliciting an inflammatory response) (Serhan et al. 2008).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H can also catalyse the hydrolysis of 5S,6S-epoxy-18(S)-HEPE to the 18(S) stereoisomer of resolvin E1 (18(S)-RvE1) (Oh et al. 2011). The E-resolvins are anti-inflammatory, pro-resolving, and non-phlogistic (that is, they mediate the clearance of leukocytes without eliciting an inflammatory response) (Serhan et al. 2008).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H can also catalyse the hydrolysis of 7S(8)-epoxy-17(R)-hydroxydocosahexaenoic acid (7S(8)-epoxy-17(R)-HDHA) to the trihydroxydocosahexaenoic acids 7(S), 8(R), 17(R)-triHDHA and 7(S), 16(R), 17(R)-triHDHA (AT-RvD1 and AT-RvD2 respectively) (Sun et al. 2007, Spite et al. 2009, Serhan et al. 2002). The D-resolvins are anti-inflammatory, pro-resolving, and non-phlogistic (that is, they mediate the clearance of leukocytes without eliciting an inflammatory response) (Serhan et al. 2008).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H can also catalyse the hydrolysis of 4S(5)-epoxy-17(R)-hydroxydocosahexaenoic acid (4S(5)-epoxy-17(R)-HDHA) to the trihydroxydocosahexaenoic acids 4(S), 11(R), 17(R)-triHDHA and 4(S), 5(R), 17(R)-triHDHA (AT-RvD3 and AT-RvD4 respectively) (Dalli et al. 2013, Serhan et al. 2002, Winkler et al. 2013, 2016). The D-resolvins are anti-inflammatory, pro-resolving, and non-phlogistic (that is, they mediate the clearance of leukocytes without eliciting an inflammatory response) (Serhan et al. 2008).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H can also catalyse the hydrolysis of 4S(5)-epoxy-17(S)-hydroxydocosahexaenoic acid (4S(5)-epoxy-17(S)-HDHA) to the trihydroxydocosahexaenoic acids 4(S), 11(R), 17(S)-triHDHA and 4(S), 5(R), 17(S)-triHDHA (RvD3 and RvD4 respectively) (Dalli et al. 2013, Serhan et al. 2002, Winkler et al. 2013, 2016). The D-resolvins are anti-inflammatory, pro-resolving, and non-phlogistic (that is, they mediate the clearance of leukocytes without eliciting an inflammatory response) (Serhan et al. 2008).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H can also catalyse the hydrolysis of 7S(8)-epoxy-17(S)-hydroxydocosahexaenoic acid (7S(8)-epoxy-17(S)-HDHA) to the trihydroxydocosahexaenoic acids 7(S), 8(R), 17(S)-triHDHA and 7(S), 16(R), 17(S)-triHDHA (RvD1 and RvD2 respectively) (Sun et al. 2007, Spite et al. 2009, Serhan et al. 2002). The D-resolvins are anti-inflammatory, pro-resolving, and non-phlogistic (that is, they mediate the clearance of leukocytes without eliciting an inflammatory response) (Serhan et al. 2008).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). LTA4H may also be able to catalyse the hydrolysis of 17R(6)-epoxy-docosahexaenoic acid (17R(16)-epoxy-DHA) to 10(R),17(R)-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid (aspirin-triggered (neuro)protectin D1, AT-(N)PD1) (Serhan et al. 2011). In human cells, AT-(N)PD1 decreased PMN migration as well as enhancing efferocytosis of apoptotic human PMN by macrophages, indicating AT-(N)PD1 as a potent anti-inflammatory proresolving molecule (Serhan et al. 2011).
Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that uses a Zn2+ cofactor to catalyse the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) (McGee & Fitzpatrick 1985). When produced in neural tissue, where it affords potent tissue protective actions, this docsanoid is called neuroprotectin D1 (NPD1).
In macrophages, lipoxygenase 12 (ALOX12:Fe2+) may abstract hydrogen from 14(S)-hydroperoxy-docosaheaenoic acid (14(S)-Hp-DHA) to form 13(S),14(S)-epoxy-DHA (Serhan et al. 2009, Dalli et al. 2013, Deng et al. 2014). This epoxy product is a central intermediate in maresin MaR1 and MaR2 and maresin conjugates in tissue regeneration (MCTR) biosyntheses (Dalli et al. 2016) as well as possessing potent proresolving activity (Dalli et al 2013).
Maresin 1 (MaR1, 7(R),14(S)-dihydroxy-docosahexaenoic acid) is the first identified maresin. It is formed by hydrolysis of 13(R),14(S)-epoxy-docosahexaenoic acid (13(R),14(S)-epoxy-DHA) by an unknown epoxide hydrolase (Serhan et al. 2009). MaR1 displays potent anti-inflammatory and pro-resolving actions (Serhan et al. 2012, Chatterjee et al. 2014). MaR1 was found to inhibit proinflammatory mediator production by inhibiting LTA4 hydrolase, thereby shifting macrophage phenotype from proinflammatory mediator to proresolving mediator production (Dalli et al. 2013).
A novel double dioxygenation product can also be formed by non-enzymatic hydrolysis of 13(R),154(S)-epoxy-DHA, namely 7(S),14(S)-dihydroxy-docosahexaenoic acid (7-epi-MaR1). Although 7-epi-MaR1 possesses some bioactivity, it displays lower anti-inflammatory and pro-resolving actions than MaR1 (Serhan et al. 2009).