Substrate-dependent modulation of the leukotriene A₄ hydrolase aminopeptidase activity and effect in a murine model of acute lung inflammation.

ABSTRACT: The aminopeptidase activity (AP) of the leukotriene A₄ hydrolase (LTA₄H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA₄H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA₄H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA₄H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA₄H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM

SUBMITTER: Lee KH 

PROVIDER: S-EPMC9177663 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature