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. 2021 Jun 12;22(12):6311. doi: 10.3390/ijms22126311

Figure 4.

Figure 4

Roles of NADH and NADPH in metabolism and antioxidant pathways. (a–c) Synthesis of NADH from NAD+ in (a) glycolysis, and (c) TCA cycle; NADPH from NADP+ in (b) PPP and (c) TCA cycle. (d) Synthesis of NADP+ from NAD+ by NAD+ kinase both in cytosol and mitochondria. (e) Oxidation of NADH by complex I is the main source of ROS inside the cell in addition to (f) the activation NOX2 that generates ROS through a reduction of oxygen using NADPH as the source of donor electrons. In brain cells, the role of NADPH is predominantly antioxidant; for instance, (g) NADPH is used by glutathione reductase to reduce oxidized glutathione, and by (h) thioredoxin reductase to reduce oxidized thioredoxin. (i) Under oxidative stress and DNA damage, PARP-1 is activated, and this is manifested by an increase in the consumption of NAD+ by PARP. (j) On the other hand, the enzymatic activity of SIRTs consumes NAD+. SIRTs catalyze the deacetylation of target proteins by converting NAD+ into NAM. Created with BioRender.com.