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

Authors :
Shen J
Wu G
Pierce BS
Tsai AL
Zhou M
Source :
The Journal of biological chemistry [J Biol Chem] 2023 Jul; Vol. 299 (7), pp. 104897. Date of Electronic Publication: 2023 Jun 07.
Publication Year :
2023

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 <superscript>2+</superscript> ) sustains the enzymatic activity. Using SCD1 labeled with Fe isotope, we further show that free Fe <superscript>2+</superscript> is incorporated into the diiron center only during catalysis. We also discover that the diiron center in SCD1 has prominent electron paramagnetic resonance signals in its diferric state, indicative of distinct coupling between the two ferric ions. These results reveal that the diiron center in SCD1 is structurally dynamic during catalysis and that labile Fe <superscript>2+</superscript> in cells could regulate SCD1 activity and hence lipid metabolism.<br />Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1083-351X
Volume :
299
Issue :
7
Database :
MEDLINE
Journal :
The Journal of biological chemistry
Publication Type :
Academic Journal
Accession number :
37290533
Full Text :
https://doi.org/10.1016/j.jbc.2023.104897