Engaging with enzymes

Reflections on Ortiz de Montellano’s passion for heme and renewal

 Ortiz De Montellano

In a recent issue of the Journal of Biological Chemistry, Paul Ortiz de Montellano, a professor in the pharmaceutical chemistry and pharmacology departments at the University of California, San Francisco, looked back on a scientific career that revolved around heme enzymes. Heme enzymes perform a wide array of functions and are involved in biosynthesis, carrying oxygen in the blood and metabolizing drugs. Ortiz de Montellano is best known in scientific circles for his extensive research on the cytochrome P450 family of enzymes and his work with heme oxygenase and heme-modifying peroxidases tied to cytochrome P450.

Born in Mexico City to the distinguished Mexican poet Bernard Ortiz de Montellano and an American mother who was a teacher from Missouri, Ortiz de Montellano grew up with two siblings. His younger sister, Ana, went on to become a writer and professor, and an older brother, Bernard, who studied to be a chemist, is now an emeritus professor of anthropology.

With a bit of help from a biology teacher he calls “phenomenal,” Ortiz de Montellano discovered a passion for science as a high schooler in San Antonio, Texas, and went on to the Massachusetts Institute of Technology for his undergraduate degree in chemistry. He says he always knew he belonged in science, but it was his brother enrolling in graduate school for chemistry at the same time that Ortiz de Montellano started his undergraduate career that sealed his choice of field.

Ortiz de Montellano went on to do his graduate work in bioorganic chemistry at Harvard University under E.J. Corey, who won the 1990 Nobel Prize in Chemistry, and Konrad Bloch, who won the 1964 Nobel Prize in Physiology. After earning his Ph.D., Ortiz de Montellano did a postdoctoral fellowship in bioorganic chemistry at the Swiss Federal Institute of Technology in Zurich, Switzerland.

The students and postdoctoral fellows in Paul Ortiz de Montellano’s laboratory when they entered the cytochrome P450 and heme world. Seated from left to right, Kathryn Prickett, Paul Ortiz de Montellano, Dianne Jassawalla. Standing from left to right, Wayne Vinson, Kent Kunze, Bruce Mico, Gary Yost and Stephen Dinizo. Kunze, Mico, Yost, and Dinizo were the founding members of the P450 team. Prickett, Jassawalla and Vinson worked on squalene biogenesis.

Ortiz de Montellano has studied a wide array of topics since he joined the University of California, San Francisco as an independent researcher in 1972. His most notable contributions have been to the study of cytochrome P450, a huge family of more than 21,000 enzymes that have a heme cofactor. That work has included studying porphyria, a rare disease that can cause neurological symptoms and skin problems from the buildup of excess porphyrins. (In normal quantities, porphyrins are used to produce heme.) Ortiz de Montellano also has researched multiple classes of hemoproteins and enzymes found in Mycobacterium tuberculosis, the bacterium which causes most cases of tuberculosis. Since tuberculosis is a leading cause of death in HIV/AIDS patients, this research was done as part of a team studying HIV/AIDS.

Ortiz de Montellano is currently considering following in his father’s footsteps and becoming a writer, perhaps of novels. He also enjoys reading about history and historical fiction and notes particular interests in the industrial revolution, military history, and the mid-1600s, during which Louis XIV and Charles II reigned.

Ortiz de Montellano says he believes it is “always important to take time to renew oneself” and has taken five sabbaticals over the years. His advice to young scientists is to keep one foot in the ideal world and one in the practical world. “One has to keep in mind that one has to eventually make a living,” he says. But he stresses that once the practicalities are taken care of, it is important to do something you love.

Photo of Alexandra Pantos Alexandra Pantos is an editorial assistant for ASBMB and former intern for ASBMB Today