Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra

Figure 1

NAD(H)—the electron donor to complex I translocating protons across the membrane by a “steam engine” like mechanism producing ATP: the most important function of mitochondria alongside proton leaks for heat and energy dissipation and signals for autophagy and apoptosis. Many mutations that affect mitochondrial complex 1, or, microtubular function and kinases and autophagy/mitophagy and radical production contribute to rare forms of ageing diseases such as PD in a vicious cycle subverting normal quality controls that affect proteosomal homeostasis. In the case of Parkinsons’, increasing NADH levels may drive excessive dopamine synthesis to toxic levels by enhancing the recycling of the cofactor for tyrosine hydroxylase.