Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5513148 | The Journal of Steroid Biochemistry and Molecular Biology | 2017 | 6 Pages |
â¢Inhibition of AMPK or PKA decreases DHCR7 activity.â¢Mutation of S14 in DHCR7 decreases activity independently of AMPK and PKA.â¢In the skin, phosphorylation of DHCR7 may divert flux from cholesterol to vitamin D synthesis.
Cholesterol is essential for survival, but too much or too little can cause disease. Thus, cholesterol levels must be kept within close margins. 7-dehydrocholesterol reductase (DHCR7) is a terminal enzyme of cholesterol synthesis, and is essential for embryonic development. Largely, DHCR7 research is associated with the developmental disease Smith-Lemli-Opitz syndrome, which is caused by mutations in the DHCR7 gene. However, little is known about what regulates DHCR7 activity. Here we provide evidence that phosphorylation plays a role in controlling DHCR7 activity, which may provide a means to divert flux from cholesterol synthesis to vitamin D production. DHCR7 activity was significantly decreased when we used pharmacological inhibitors against two important kinases, AMP-activated protein kinase and protein kinase A. Moreover, mutating a known phosphorylated residue, S14, also decreased DHCR7 activity. Thus, we demonstrate that phosphorylation modulates DHCR7 activity in cells, and contributes to the overall synthesis of cholesterol, and probably vitamin D.