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Roles as Ultradian Oscillators of the Cells Biological Clock

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ECTO-NOX Proteins

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Abstract

The homodimeric, growth-related and time-keeping constitutive hydroquinone oxidase ENOX1 of the eukaryotic cell surface capable of oxidizing extracellular NAD(P)H and intracellular hydroquinones exhibits properties of the ultradian driver of the biological 24-h circadian clock by exhibiting a complex 2 + 3 set of oscillations with a period length of 24 min (repeats 60 times over 24 h). The oscillations require bound copper, are recapitulated by aqueous solutions of copper salts and appear to derive from 30 to 40 s periodic variations in the ratios of ortho and para nuclear spins of the paired hydrogen atoms of the elongated octahedral structure of the ENOX1 protein-bound copperII hexahydrates. By functioning in the manner of limit oscillators, these 30–40 s oscillations appear to generate the 24-min periodicity in the manner of a carrier wave. The ortho–para oscillations are highly synchronous through self-generated very low frequency electromagnetic fields which also serve to phase ENOX1/copperII oscillations. The synchronized populations of water molecules give rise to oscillatory electromagnetic fields that apparently are perceived by adjacent water molecules to create a collectively coherent synchronous system capable of extending over very long distances. The period length of the ENOX oscillations is temperature independent and entrained by light, melatonin, lithium, and caffeine. COS cells transformed with specific ENOX variants where specific cysteine codons are replaced by alanine codons yield circadian periods of 22, 34, or 42 h respectively, based on activity of glyceraldehyde-3-dehydrogenase in response to ENOX oscillations with period lengths of 22, 36, or 42 min. That the oscillations result from physical rather than chemical events accounts for the temperature independence of the period length of clock-related phenomena. Also, the period length of both the ENOX and copperII oscillations in D2O is increased to 30 min in keeping with the 30-h circadian day exhibited by organisms grown in deuterium oxide. An opportunity to link the ultradian ENOX oscillation to downstream activation of clock genes may be provided by responses of transcriptional factors to levels of NADH and especially to NAD+ generated by ENOX oscillations. Adverse effects resulting from chronic disturbances or disruptions of circadian rhythms by repeated rephrasing of the ENOX cycle may include an increased risk of cancer.

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    D. James Morré & Dorothy M. Morré

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Morré, D.J., Morré, D.M. (2012). Roles as Ultradian Oscillators of the Cells Biological Clock. In: ECTO-NOX Proteins. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3958-5_6

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