Free ferrous ions sustain activity of mammalian stearoyl-CoA desaturase-1.

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 (Fe²⁺) sustains the enzymatic activity. Using SCD1 labeled with Fe isotope, we further show that free Fe²⁺ is incorporated into the diiron center only during catalysis. We also discover that the diiron center in SCD1 has promi

SUBMITTER: Shen J 

PROVIDER: S-EPMC10359943 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature