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2015 Abstracts

The Role of Pas Kinase in NAD Homeostasis

Daniel Barnett, Brigham Young University

Life Sciences

Approximately one-third of US adults have metabolic disease, increasing their risk for diabetes, cancers and neurodegenerative disease ( At the heart of these diseases are imbalances in the cellular redox state. The cofactor NAD(P), commonly known as niacin, is required for over 300 essential reactions in the cell and is largely responsible for the cellular redox state. NAD kinase regulates the NAD to NADP ratio, an important ratio for controlling cellular redox state and central metabolism. Herein we provide evidence that PAS kinase, a nutrient sensing kinase required for glucose homeostasis, phosphorylates NAD kinase. We are currently investigating the effect of this phosphorylation on the function of NAD kinase both in vitro and in vivo by measuring NAD kinase activity and associated phenotypes. This research will increase our understanding of how cells regulate central metabolism. In addition, because PAS kinase is a nonessential protein, it may prove to be an invaluable treatment target for regulating NAD(P) levels and controlling cellular redox state. This may lead to therapeutic targets for cancer and metabolic diseases such as diabetes.