Scientists have discovered new targets for a biomedically important enzyme, according to a report online this week in Nature Chemical Biology. The research provides insight into a pathway to salvage amino acids in the kidney.

Dipeptidyl peptidase 4 (DPP4) is an abundant enzyme that cuts proteins containing specific amino acids near the end of a protein. The identification of one known DPP4 physiological target has recently led to antidiabetic drug therapy that targets this enzyme. While experiments with DPP4 have identified several substrates for this important enzyme, few studies have confirmed these results in a physiological system. To fully understand the risks and benefits of DPP4 based therapies, it is important to identify other pathways that might be affected.

Alan Saghatelian and colleagues performed protein profiling on the kidneys of mice with variable DPP4 activity and identified several new substrates for the enzyme. In addition, the authors provide evidence that DPP4 works together with another class of enzymes called aminopeptidases to process proteins in the kidney. It remains unclear whether the resulting peptides have a specific physiological function in the kidney or whether they are simply produced and reabsorbed for reuse within the body.