Free Ferrous Ions Sustain Activity of Mammalian Stearoyl-CoA Desaturase-1

Authors

Jiemin Shen
Gang Wu
Brad S Pierce
Ah-Lim Tsai
Ming Zhou

Publication Date

7-1-2023

Journal

Journal of Biological Chemistry

Abstract

Mammalian stearoyl-CoA desaturase-1 (SCD1) introduces a double-bond to a saturated long-chain fatty acid in a reaction catalyzed by a diiron center. The diiron center is well-coordinated by conserved histidine residues and is thought to remain with the enzyme. However, we find here that SCD1 progressively loses its activity during catalysis and becomes fully inactive after about nine turnovers. Further studies show that the inactivation of SCD1 is due to the loss of an iron (Fe) ion in the diiron center and that the addition of free ferrous ions (Fe

Keywords

diiron; electron paramagnetic resonance (EPR); labile iron; lipid desaturation; metalloenzyme; stearoyl-CoA desaturase (SCD)