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Biological effects of deuteronation: ATP synthase as an example.

Olgun A - Theor Biol Med Model (2007)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biochemistry Laboratory, TSK Rehabilitation Center, Gulhane School of Medicine, Bilkent Ankara, Turkey. aolgun@yahoo.com

ABSTRACT

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.

Theory and discussion: 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.

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.

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Related in: MedlinePlus

Proton/deuteron passage from F0 of ATP synthase in mitochondria. Protons enter the cytoplasmic half-channel and reach Asp61 on subunits c. Protonated Asp61 moves into the lipid bilayer. When protonated Asp61 reaches the matrix half-channel, it is deprotonated by the stator charge of Arg210 on subunit a. A temporary stutter of the rotor is expected during the passage of deuteron. *The ratio of deuterons (D+) to protons (H+) is ~1:15000.
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Figure 1: Proton/deuteron passage from F0 of ATP synthase in mitochondria. Protons enter the cytoplasmic half-channel and reach Asp61 on subunits c. Protonated Asp61 moves into the lipid bilayer. When protonated Asp61 reaches the matrix half-channel, it is deprotonated by the stator charge of Arg210 on subunit a. A temporary stutter of the rotor is expected during the passage of deuteron. *The ratio of deuterons (D+) to protons (H+) is ~1:15000.

Mentions: F0 is hydrophobic, spans the mitochondrial inner membrane and is estimated to have ~10 c subunits. The c subunits form a wheel-like structure that is a part of the "rotor". In E. coli, there is an aspartic acid residue in the middle of the second helix of subunit c. Subunit a of F0 binds to the outside of the rotor and forms part of the "stator". There are two proton half-channels (termed cytosolic and matrix in mitochondria) of "subunit a", on the interface between subunits c and a. The proton concentration in the intermembrane space is ~25 fold higher than that in the matrix. The entry of protons into the cytoplasmic half-channel is also facilitated by a +0.14V membrane potential, which increases the proton concentration in the orifice of this channel. Protons entering the cytoplasmic half-channel reach Asp61. Protonation neutralizes this residue, which moves into the lipid bilayer, finally turning the rotor. However, throughout the whole rotation of the rotor, an Asp61 facing the matrix half-channel should be deprotonated thanks to the stator charge of Arg210 on subunit a (Figure 1). If both Asp61 sites facing half-channels are protonated at the same time, the rotor turns freely in both directions [3-7].


Biological effects of deuteronation: ATP synthase as an example.

Olgun A - Theor Biol Med Model (2007)

Proton/deuteron passage from F0 of ATP synthase in mitochondria. Protons enter the cytoplasmic half-channel and reach Asp61 on subunits c. Protonated Asp61 moves into the lipid bilayer. When protonated Asp61 reaches the matrix half-channel, it is deprotonated by the stator charge of Arg210 on subunit a. A temporary stutter of the rotor is expected during the passage of deuteron. *The ratio of deuterons (D+) to protons (H+) is ~1:15000.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1808445&req=5

Figure 1: Proton/deuteron passage from F0 of ATP synthase in mitochondria. Protons enter the cytoplasmic half-channel and reach Asp61 on subunits c. Protonated Asp61 moves into the lipid bilayer. When protonated Asp61 reaches the matrix half-channel, it is deprotonated by the stator charge of Arg210 on subunit a. A temporary stutter of the rotor is expected during the passage of deuteron. *The ratio of deuterons (D+) to protons (H+) is ~1:15000.
Mentions: F0 is hydrophobic, spans the mitochondrial inner membrane and is estimated to have ~10 c subunits. The c subunits form a wheel-like structure that is a part of the "rotor". In E. coli, there is an aspartic acid residue in the middle of the second helix of subunit c. Subunit a of F0 binds to the outside of the rotor and forms part of the "stator". There are two proton half-channels (termed cytosolic and matrix in mitochondria) of "subunit a", on the interface between subunits c and a. The proton concentration in the intermembrane space is ~25 fold higher than that in the matrix. The entry of protons into the cytoplasmic half-channel is also facilitated by a +0.14V membrane potential, which increases the proton concentration in the orifice of this channel. Protons entering the cytoplasmic half-channel reach Asp61. Protonation neutralizes this residue, which moves into the lipid bilayer, finally turning the rotor. However, throughout the whole rotation of the rotor, an Asp61 facing the matrix half-channel should be deprotonated thanks to the stator charge of Arg210 on subunit a (Figure 1). If both Asp61 sites facing half-channels are protonated at the same time, the rotor turns freely in both directions [3-7].

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biochemistry Laboratory, TSK Rehabilitation Center, Gulhane School of Medicine, Bilkent Ankara, Turkey. aolgun@yahoo.com

ABSTRACT

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.

Theory and discussion: 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.

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.

Show MeSH
Related in: MedlinePlus