Skip to main content

Altered metabolism and disease

Jul. 25, 2017, 8:00 AM

by Laura Daniel

Mutations in cytochrome P450 enzymes can result in altered metabolism leading to disease. One of the most common of all inherited defects is congenital adrenal hyperplasia (CAH), which leads to changes in secondary sex characteristics.

CAH is often caused by mutations in P450 21A2, which metabolizes progesterone and 17alpha-hydroxyprogesterone, an intermediary in the formation of cortisol, androgens, and estrogens.

F. Peter Guengerich, Ph.D., Martin Egli, Ph. D., and colleagues now report a structure of human P450 21A2 bound to its substrate 17alpha-hydroxyprogesterone.

Their June 30 report, which investigated 12 variants of the human enzyme, was selected by The Journal of Biological Chemistry as an “Editor’s Pick” and by the Faculty of 1000 as a “must read.”

The researchers linked low catalytic activity of the variants with single amino acid substitutions and found that the rate-limiting step in catalytic efficiency was breaking the carbon-hydrogen bond.

This study advances what is known about P450 21A2 and the mechanisms involved in a wide range of CAH-causing mutations.

This research was supported by National Institutes of Health grant GM103937.

Send suggestions for articles to highlight in Aliquots and any other feedback about the column to aliquots@vanderbilt.edu

Recent Stories from VUMC News and Communications Publications

Marissa Benchea has CF, and she is one of hundreds of thousands of adults not only surviving but thriving with a chronic childhood disease.

Vanderbilt Medicine

Marissa Benchea has CF, and she is one of hundreds of thousands of adults not only surviving but thriving with a chronic childhood disease.

One hundred years ago, multiple “waves” of a deadly flu swept across the world.

Vanderbilt Medicine

One hundred years ago, multiple “waves” of a deadly flu swept across the world.

A diagnosis of cancer at any age is tragic, but during the adolescent and young adult years, it’s especially complicated.

Hope

A diagnosis of cancer at any age is tragic, but during the adolescent and young adult years, it’s especially complicated.

Karen Dyer Young cares for patients and members of the Dayani Center who have or are recovering from cancer or a stem cell transplant.

Momentum

Karen Dyer Young cares for patients and members of the Dayani Center who have or are recovering from cancer or a stem cell transplant.

more