Donald Becker, PhD Internal Advisory Committee
Professor; Director, Redox Biology Center
Department of Biochemistry
University of Nebraska–Lincoln
N258 Beadle Center
Lincoln, NE 68588-0664
Phone: (402)472-9307 | Email: firstname.lastname@example.org
The amino acid proline has multifaceted roles including carbon and nitrogen flux, protein synthesis, osmolyte balance, and stress protection. There is growing evidence that proline metabolism can influence cell survival outcomes in microorganisms, plants, and animals. Proline effects diverse signaling pathways by the generation of reactive oxygen species (ROS) due to proline oxidation being coupled to the respiratory electron transport chain and contributing to cellular bioenergetics. Overall proline has become a very important metabolite that is thought to be involved in many cellular processes that impact human health and disease.
The overall goal of our research is to understand the mechanisms of proline metabolic enzymes and how proline metabolism impacts stress response and the intracellular redox environment. All organisms convert proline to glutamate in two enzymatic steps. In the first step, proline is oxidized to ∆1-pyrroline-5-carboxylate (P5C) by the flavin-dependent enzyme PRODH. P5C is then hydrolyzed nonenzymatically to glutamic semialdehyde (GSA), which is oxidized to glutamate by the NAD dependent enzyme, P5C dehydrogenase (P5CDH). In Gram-negative bacteria, the PRODH and P5CDH domains are fused onto the same polypeptide called the proline utilization A (PutA) protein. Proline biosynthesis from glutamate involves three enzymatic steps. The initial two steps are catalyzed by g-glutamyl kinase (GK) and g-glutamyl phosphate reductase (GPR). GK generates g-glutamyl phosphate, which is then reduced by GPR to produce GSA. In bacteria and lower eukaryotes such as yeast, GK and GPR are discrete monofunctional enzymes. In animals and plants, the GK and GPR domains are fused together into the bifunctional enzyme P5C synthase (P5CS). After GSA cyclizes to P5C, P5C is reduced to proline by P5C reductase (P5CR).