Biological effects of deuteronation: ATP synthase as an example

BACKGROUND: In nature, deuterium/hydrogen ratio is ~1/6600, therefore one of ~3300 water (H(2)O) molecules is deuterated (HOD + D(2)O). In body fluids the ratio of deuterons to protons is ~1/15000 because of the lower ionization constant of heavy water. The probability of deuteronation rather than protonation of Asp 61 on the subunit c of F(0 )part of ATP synthase is also ~1/15000. The contribution of deuteronation to the pKa of Asp 61 is 0.35. THEORY AND DISCUSSION: In mitochondria, the release of a deuteron into the matrix side half-channel of F(0 )is likely to be slower than that of a proton. As another example, deuteronation may slow down electron transfer in the electron transport chain (ETC) by interfering with proton coupled electron transport reactions (PCET), and increase free radical production through the leakage of temporarily accumulated electrons at the downstream complexes. CONCLUSION: Deuteronation, as exemplified by ATP synthase and the ETC, may interfere with the conformations and functions of many macromolecules and contribute to some pathologies like heavy water toxicity and aging.