Divergent Reactivity of Hemoglobin Isoforms α2Aß2 and α2Dß2 from Meleagris gallopavo in Native and Fatty Acid-Modified States.

Meleagris gallopavo (turkey) coexpresses distinct hemoglobin (Hb) isoforms, Hb α2Aß2 (HbA) and α2Dß2 (HbD), at a ratio of ∼3:1 (HbA:HbD). Herein, the reactivities of HbA and HbD were investigated in their native and free fatty acid (FFA)-modified states. Results indicated that HbD displays elevated autoxidation (kox) and an increased propensity to oxidize lipids in its reduced (oxy) and oxidized (met) forms. Interestingly, metHbD displayed less heme-globin cross-linking compared to HbA. Regarding FFA-modified Hb, we found that an FFA mixture and linoleic acid (LA) produced a bis-histidyl ferric (Bis-His) Hb species, decreasing the ability of Hb to oxidize lipids. Using molecular docking, we found LA to hydrogen bond with ß Arg C6, found at the α1ß2 interface, but the extent of Bis-His formation differs between HbA and HbD. Our findings suggest HbA displays elevated oxidative stability compared to HbD and that FFA may act as allosteric effectors of metHb.