The deficiency of an enzyme leads to severe head deformities and ambiguous sex organs in babies born with Antley-Bixler syndrome, scientists have found.
The team, composed of researchers from The University of Texas Health Science Center San Antonio, the Medical College of Wisconsin and Charles University in Prague, solved the atomic structure of this human enzyme with an impressive name - NADPH-cytochrome P450 reductase, abbreviated CYPOR.
The group is the first to visualize and depict the structure of the human version of CYPOR. The scientists also reported the structure of two mutations of human CYPOR that result in congenital deformities.
"Human syndromes are caused by the deficiency of this enzyme," Bettie Sue Masters, Ph.D., D.Sc., M.D. (Hon.), professor of biochemistry and the Robert A. Welch Foundation Distinguished Professor in Chemistry at the UT Health Science Center, said.
"The two mutations that we characterized are responsible for severe craniofacial and steroid-production defects in humans, the latter leading to sexual ambiguities," she stated.
In the body, steroids are produced for many important functions. In CYPOR deficiency, these steroidal malfunctions are related to deformed sexual organs and other defects.
In previously published research from Dr. Masters' laboratory, addition of a riboflavin (vitamin B2) derivative reversed the defects in the mutated enzymes; this is because the vitamin makes this particular enzyme work, producing metabolites. Metabolites are the products of enzyme-generated reactions.
This reversal of CYPOR defects by a riboflavin derivative is yet to be investigated in animals or humans. Foods such as liver, herbs, almonds, wheat bran, fish and cheese are rich in riboflavin.
The structural basis for human CYPOR deficiency is described in the August 4 edition of Proceedings of the National Academy of Sciences.