Fig. 3.

Coordination of intracellular redox status with intermediary metabolic pathways. Pyridine nucleotide balance is influenced by glucose-metabolizing enzymes such as glucose-6-phosphate dehydrogenase (G6PDH) and aldose reductase (AR). AR also utilizes NADPH in the reduction of aldehydes to their corresponding alcohols. Other cytosolic proteins that regulate NADPH levels include NADPH oxidases (Nox) and nitric oxide synthases (NOS). In the mitochondrion, the tricarboxylic acid cycle (TCA) as well as metabolism of aldehydes by aldehyde dehydrogenase 2 (ALDH2) can contribute to the production of NADH, which is not only used for energy transfer but can be converted to NADPH through the actions of nicotinamide nucleotide transhydrogenase (NNT). The cytosolic enzymes malic enzyme (ME) and NADP^þ-dependent isocitrate dehydrogenase (NADP^þ-IDH) utilize metabolic intermediates created in the TCA cycle to produce NADPH.