NADP+/NADPH in Metabolism and its Relation to Cardiovascular Pathologies

Abstract: The nicotinamide adenine dinucleotide phosphate (NADP+/NADPH) redox couple serves as a substrate or cofactor for many enzymes to maintain cellular redox homeostasis as well as to regulate biosynthetic metabolism. The deficiency or imbalance of NADP+/NADPH redox couple is strongly associated with cardiovascular-related pathologies. An imbalance in the NADP+/NADPH ratio can lead to either oxidative or reductive stress. Reductive stress complicates the cellular redox environment and provides new insights into the cellular redox state. Newly discovered biosynthetic enzymes and developed genetically encoded biosensors provide technical support for studying how cells maintain a compartmentalized NADP(H) pool. NADP(H) plays an important role in cardiovascular pathologies. However, whether NADP(H) is injurious or protective in these diseases is uncertain, as either deficiency or excess NADP(H) levels can lead to imbalances in cellular redox state and metabolic homeostasis, resulting in energy stress, redox stress, and ultimately disease state. Additional study of the replicative regulatory network of NADP(H) metabolism in different compartments, and the mechanisms by which NADP(H) regulates redox state and metabolism under normal and pathological conditions, will develop the targeted and novel therapies based on NADP(H) metabolism.