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SCD

The enzyme stearoyl-CoA desaturase (SCD; EC 1.14.99.5), a delta-9 desaturase, responsible for the synthesis of monounsaturated fatty acids (MUFA) has been shown to be a significant player in mouse metabolism. SCD is bound to the endoplasmic reticulum (ER), a major membrane constituent of eukaryotic cells. It is associated with the multicomponent electron transport chain in liver microsomes. Membrane bound desaturases are proposed to consist of four membrane spanning domains with the N and C termini (as well as the catalytic site) being orientated toward the cytosolic side of the membrane. MUFAs are synthesised via an aerobic process from saturated fatty acyl precursors by a three-component enzyme system involving flavoproteinNADH-dependent cytochrome b5 reductase, cytochrome b5, and SCD. Sterol responsive element binding protein-1c (SREBP-1c) appears to play an important role in the transcriptional regulation of SCD.
Transcriptional activation of genes containing a sterol responsive element (SRE) are known to be under the regulation of sterols through modulation of proteolytic maturation of SREBP-1 and SREBP-2. SREBPs are in the ER membrane of a wide variety of tissues and SREBP-1c preferentially enhances the transcription of genes essential for fatty acid synthesis in the liver, including SCD1, whilst SREBP-2 activates genes involved in cholesterol biosynthesis. SREBP-1c is positively regulated by insulin at the transcriptional level and it is up-regulated in mouse models of hyperinsulinemia and down-regulated in models with insulindeficiency, such as fasting and streptozotocin-induced diabetes. SREBP-1c deficient models have a decreased hepatic SCD1 mRNA expression whilst mice expressing a constitutively active form have increased expression. SCD1 may also be regulated by factors that influence its stability or degradation. ATPase p97 is a protein involved in the regulation of proteasome-dependent degradation of SCD1. It has been reported that ATPase p97 mRNA expression in visceral and subcutaneous adipose tissue is similar between control and morbidly obese subjects. The mRNA expression of ATPase p97 appears to be depot specific with significantly higher expression being reported in visceral compared to subcutaneous adipose tissue.

References

1.Hodson L,et al. Prog Lipid Res. 2013;52(1):15–42.

Metabolic Enzyme/Protease

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