Renalase was an enzyme of unknown biological function for almost a decade. While it was described as a new renal hormone secreted into blood by the kidney to consume adrenaline and thereby lower blood pressure and slow the heart rate, no convincing demonstration of this activity was ever made. Based on a recent discovery by the principal investigator, it appears that the true function has nothing to do with blood pressure. Renalase instead appears to be a salvage enzyme that prevents the loss of a molecule at the heart of metabolism in all living organisms. This molecule has a tendency to alter its structure in a way that makes it useless in metabolism. Renalase prevents the accumualtion of the inactive molecules, saving or salvaging them, by turning them back into the correct, active structure. This function for renalase involves unprecedented enzyme chemistry that is likely to be found to be pervasive, utilized by many if not all forms of life. The intent of this award is to establish a foundational understanding of this curious new chemical activity. As new enzyme chemistry, the investigation of renalase will be an excellent platform to teach graduate students about enzymology. Moreover, the principal investigator will integrate the discovery of new examples of this activity into an Introductory Biochemistry Laboratory class such that undergraduates can participate directly in the advancement of this research by making genuine scientific discoveries in the laboratory classroom.
This award from the National Science Foundation, Division of Chemistry, Chemistry of Life Processes Program is funding Dr. Graham R. Moran from the University of Wisconsin-Milwaukee to characterize a newly discovered enzyme, renalase that would appear to be important for efficient metabolic activity in living organisms. The award will fund a range of research activities that will define the chemical mechanism of renalase, the structural basis for the activity, and the metabolic importance of this activity. The methods employed will use a combination of rapid-mixing pre-steady state spectrophotometric kinetic techniques, structural elucidation of substrate analog and product enzyme complexes, numerous biophysical approaches that take advantage of the spectrophotometric reporting power of the enzyme's cofactor and site directed mutagenesis of conserved active site amino acids. In addition, Dr. Moran intends to develop an undergradaute laboratory course in which students discover new examples of this chemistry in a broad range of organisms such that the course will provide new avenues of investigation by which the full importance of and context for this activity can be established.
