Biological effects of deuteronation: ATP synthase as an example.
BACKGROUND
In nature, deuterium/hydrogen ratio is approximately 1/6600, therefore one of approximately 3300 water (H2O) molecules is deuterated (HOD + D2O). In body fluids the ratio of deuterons to protons is approximately 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 F0 part of ATP synthase is also approximately 1/15000. The contribution of deuteronation to the pKa of Asp 61 is 0.35.
In mitochondria, the release of a deuteron into the matrix side half-channel of F0 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.


CONCLUSIONS
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.
Olgun
Abdullah
A
Biochemistry Laboratory, TSK Rehabilitation Center, Gulhane School of Medicine, Bilkent Ankara, Turkey. aolgun@yahoo.com
D025181:ATP Synthetase Complexes / Q000737:chemistry* / Q000378:metabolism*; D003903:Deuterium / Q000737:chemistry* / Q000494:pharmacology*; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008954:Models, Biological
D003903:Deuterium; D025181:ATP Synthetase Complexes