Localization of arachidonate 12-lipoxygenase in parenchymal cells of porcine anterior pituitary.

Ueda, Natsuo; Hiroshima, Akinori; Natsui, Kiyoshi; Shinjo, Fukiko; Yoshimoto, Tanihiro; Yamamoto, Shozo; Gerozissis, Kyriaki; Dray, F.

doi:10.1016/s0021-9258(19)39977-6

Cited by 40 publications

(1 citation statement)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It presents a high degree (86%) of sequence conservation with rabALOX15, but much less similarity with hALOX12 (66%). This porcine LOX was purified from the cytosolic fraction of leukocytes [ 37 ], and it was later also mainly found in the anterior pituitary gland of pigs [ 38 ]. As with the other ALOX15 orthologs, pigALOX15 presents dual specificity when reacting with AA.…”

Section: Introductionmentioning

confidence: 99%

Hydroperoxidation of Docosahexaenoic Acid by Human ALOX12 and pigALOX15-mini-LOX

Canyelles-Niño

González‐Lafont

Lluch

2023

IJMS

View full text Add to dashboard Cite

Human lipoxygenase 12 (hALOX12) catalyzes the conversion of docosahexaenoic acid (DHA) into mainly 14S-hydroperoxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid (14S-H(p)DHA). This hydroperoxidation reaction is followed by an epoxidation and hydrolysis process that finally leads to maresin 1 (MaR1), a potent bioactive specialized pro-resolving mediator (SPM) in chronic inflammation resolution. By combining docking, molecular dynamics simulations, and quantum mechanics/molecular mechanics calculations, we have computed the potential energy profile of DHA hydroperoxidation in the active site of hALOX12. Our results describe the structural evolution of the molecular system at each step of this catalytic reaction pathway. Noteworthy, the required stereospecificity of the reaction leading to MaR1 is explained by the configurations adopted by DHA bound to hALOX12, along with the stereochemistry of the pentadienyl radical formed after the first step of the mechanism. In pig lipoxygenase 15 (pigALOX15-mini-LOX), our calculations suggest that 14S-H(p)DHA can be formed, but with a stereochemistry that is inadequate for MaR1 biosynthesis.

show abstract

Section: Introductionmentioning

confidence: 99%