Abstract
Stearoyl-coenzyme A desaturase (SCD) catalyzes the desaturation of saturated fatty acids to monounsaturated fatty acids in mammalian cells. Currently, there are four known enzymatic isoforms (SCD1-SCD4) in the mouse genome. The physiological roles for multiple SCD isoforms and their substrate specificities are unknown at present. We report here distinct substrate specificities for the mouse SCD isoforms. Each SCD isoform was able to complement the ole1 mutation in Saccharomyces cerevisiae through heterologous expression of transgenic SCD. Fatty acid analysis showed that mouse SCD1, SCD2, and SCD4 desaturate both C18:0 and C16:0, whereas mouse SCD3 uses C16:0 but not C18:0. We identify SCD3 as a mammalian palmitotyl-CoA Delta9-desaturase, and its existence in mouse helps explain distinct physiological roles for each SCD isoform.
Highlights
Stearoyl-coenzyme A desaturase (SCD) catalyzes the desaturation of saturated fatty acids to monounsaturated fatty acids in mammalian cells
We demonstrate in this study that SCD1, SCD2, and SCD4
To study the function of mouse SCD genes (SCD1– SCD4), the open reading frames of the genes were subcloned in the episomal yeast expression vector p426GPD, which encodes uracil prototrophy under the constitutive glyceraldehyde-3-phosphate dehydrogenase promoter
Summary
Stearoyl-coenzyme A desaturase (SCD) catalyzes the desaturation of saturated fatty acids to monounsaturated fatty acids in mammalian cells. There are four known enzymatic isoforms (SCD1–SCD4) in the mouse genome. The physiological roles for multiple SCD isoforms and their substrate specificities are unknown at present. We report here distinct substrate specificities for the mouse SCD isoforms. Each SCD isoform was able to complement the ole mutation in Saccharomyces cerevisiae through heterologous expression of transgenic SCD. Fatty acid analysis showed that mouse SCD1, SCD2, and SCD4 desaturate both C18:0 and C16:0, whereas mouse SCD3 uses C16:0 but not C18:0. We identify SCD3 as a mammalian palmitotyl-CoA D9-desaturase, and its existence in mouse helps explain distinct physiological roles for each SCD isoform.—Miyazaki, M., S.
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