Biomaterial Database

Free ferrous ions sustain activity of mammalian stearoyl-CoA desaturase-1. 2023

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

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.

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 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 Fe2+ in cells could regulate SCD1 activity and hence lipid metabolism.

UI	MeSH Term	Description	Entries
D007501	Iron	A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.	Iron-56,Iron 56
D008322	Mammals	Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.	Mammalia,Mammal
D002413	Cations, Divalent	Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.	Divalent Cations
D005227	Fatty Acids	Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)	Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013230	Stearoyl-CoA Desaturase	An enzyme that catalyzes the formation of oleoyl-CoA, A, and water from stearoyl-CoA, AH2, and oxygen where AH2 is an unspecified hydrogen donor.	Stearyl-CoA Desaturase,Stearate Desaturase,delta-9 Desaturase,Desaturase, Stearate,Desaturase, Stearoyl-CoA,Desaturase, Stearyl-CoA,Desaturase, delta-9,Stearoyl CoA Desaturase,Stearyl CoA Desaturase,delta 9 Desaturase
D050356	Lipid Metabolism	Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.	Metabolism, Lipid
D055162	Biocatalysis	The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.