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ENOX Proteins, Copper Hexahydrate-Based Ultradian Oscillators of the Cells’ Biological Clock

  • Chapter
Ultradian Rhythms from Molecules to Mind

Abstract

A homodimeric, growth-related and time-keeping hydroquinone [NAD(P)H] oxidase of the mammalian (and plant) cell surface with a binuclear copper center and protein disulfide-thiol interchange activity has characteristics of an ultradian driver of the biological 24h circadian clock. A member of the ECTO-NOX or ENOX protein family, the constitutive ENOX, EN0X1 (EntrezGene ID 55068 NCBI Gen Bank accession Number EF432052), exhibits a recurring complex 2 + 3 set of oscillations in secondary structure, enzymatic activity and redox potential with a period length of 24min (repeats 60 times over 24h). The period length is temperature independent and entrained by light, melatonin and low frequency EMF. COS cells transformed with ENOX2 (EntrezGene ID 10495) where specific cysteine codons were replaced by alanine codons, ENOX2 oscillations with period lengths of 22, 36 or 42min yielded circadian periods of 22, 36 or 42h respectively, based on activity of glyceraldehyde-3-phosphate dehydrogenase. The oscillations require bound copper and are recapitulated in solution by copper salts. The period length of both the ENOX and copper II oscillations in D2O is increased to 30min (Organisms grown in deuterium oxide exhibit a 30h circadian day.). The oscillatory pattern appears to be determined by periodic variations in the ratios of ortho and para nuclear spins of the paired hydrogen or deuterium atoms of the elongated octahedral structure of the protein bound copper II hexahydrate as determined by spectroscopic analyses. That the oscillations result from physical rather than chemical events account, for the first time, for the temperature independence of the period length of clock-related pheonomena.

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  1. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 201 S. University Street, West Lafayette, IN, 47907, USA

    D. J. Morré & D. M. Morré

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Morré, D.J., Morré, D.M. (2008). ENOX Proteins, Copper Hexahydrate-Based Ultradian Oscillators of the Cells’ Biological Clock. In: Lloyd, D., Rossi, E.L. (eds) Ultradian Rhythms from Molecules to Mind. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8352-5_2

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