Vitamin D Metabolism
Research at the University of Wisconsin — Madison has revealed the complex chemical pathway of Vitamin D utilization in the kidneys, reports Kaine Korzekwa on the website www.medicalxpress.com. While small quantities of Vitamin D metabolites are produced independently by bone and skin cells, these have only local effect.
The Journal of Biological Chemistry describes the research as showing that “a kidney-specific generic control module in mice governs endocrine regulation of the cytochrome P450 gene essential for Vitamin D activation. Published online on August 14, the research entitled “A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D activation” uses “new mouse models created through CRISPR gene editing technology to identify this regulatory feature of the gene,” Korzekwa says.
Vitamin D is actually a hormone much like endocrine gland products, but is partially activated and turned into the intermediate metabolite calcidiol in the liver and then into calcitriol in the kidneys. It then enters the circulatory system and is transported all over the body, having an impact on multiple organs and biological processes.
The presence of both calcium and phosphate in the kidneys determines the production of two substances, the hormone PTH and fibroblast growth factor 23. These, in turn, control the gene that turns calcidiol into calcitriol.
Professor J. Wesley Pike of the University of Wisconsin biochemistry laboratory said, “Hector DeLuca discovered the active vitamin D metabolite in the early ’70s, building upon what his mentor Harry Steenbock had done several years before him. He discovered, among other important findings, that vitamin D needed to be modified in the body to more active forms, and that this conversion was regulated by hormones, including the dominant regulator parathyroid hormone (PTH). Beyond this, we really had no idea mechanistically how any of these hormones that regulate vitamin D activation actually worked. This molecular depth is important, because if you want to perturb the synthesis of the vitamin D hormone therapeutically in the future, you have to delineate and then understand the molecular steps that are involved that govern its production. And that’s what we’ve done.”
The research now enables the examination of illnesses that have a basis in mutations of the Vitamin D activation process. Diseases in which inflammation plays a critical part, including multiple sclerosis, kidney disease, autoimmune diseases and certain cancers are impacted by abnormally low calcitriol levels due to genetic errors in the pathway.
“The biology of Vitamin D is constantly being furthered,” Pike continued, “but our work on this regulatory aspect represents the last component of the Vitamin D puzzle. We have pried the lid open just enough now so that future work is likely to lead to a firmer understanding of how Vitamin D is produced and regulated. Now that the lid’s been lifted, it will be exciting to look inside and see what really is going on.”
