inovmedИнновационная медицина КубаниInnovative Medicine of Kuban2541-9897Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 110.35401/2541-9897-2022-25-4-82-89inovmed-607Research ArticleЛЕКЦИИLECTURESМетаболическое влияние на циркадные осцилляции pH и Eh в моче и слюнеMetabolic influence on circadian oscillations рH and Eh in urine and salivahttps://orcid.org/0000-0002-3923-7844ТатевосянА. С.TatevosyanA. S.

 Татевосян Артур Сергеевич, д. м. н., профессор кафедрыурологии

 350063, Краснодар, ул. М. Седина, 4 

 Arthur S. Tatevosyan, Dr. Sci. (Med.), Professor, Department of Urology

 4, M. Sedina str., Krasnodar, 350063 

artur-krasnodar@bk.ruhttps://orcid.org/0000-0002-1787-0040БыковИ. М.BykovI. M.

 Быков Илья Михайлович, д. м. н., заведующий кафедройфундаментальной и клинической биохимии

 350063, Краснодар, ул. М. Седина, 4 

 Ilya M. Bykov, Dr. Sci. (Med.), Professor, Head of the Department of Basic and Clinical Biochemistry 

4, M. Sedina str., Krasnodar, 350063 

https://orcid.org/0000-0001-9400-8668ГубареваД. А.GubarevaD. A.

 Губарева Диана Артуровна, ассистент кафедры профилактики заболеваний, здорового образа жизни и эпидемиологии 

 350063, Краснодар, ул. М. Седина, 4 

 Diana A. Gubareva, Assistant of the Department of Disease Prevention, Healthy Lifestyle and Epidemiology 

4, M. Sedina str., Krasnodar, 350063 

Кубанский государственный медицинский университетРоссияKuban State Medical University Russian Federation202230122022048289Copyright © Татевосян А.С., Быков И.М., Губарева Д.А., 20222022Татевосян А.С., Быков И.М., Губарева Д.А.Tatevosyan A.S., Bykov I.M., Gubareva D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.innovmedkub.ru/jour/article/view/607

Моча и слюна наиболее доступные жидкости для исследований циркадных осцилляций, когерентных с активностью протекающих метаболических процессов, которые характеризуются изменением скорости и направленности образования протонов (Н+) и электронов (ē). Существующий баланс кислотно-основного состояния (рН) и окислительно-восстановительного потенциала (Eh) является важным показателем гомеостаза, отражающим состояние энергетического обмена веществ, т. е. процесс диссимиляции. Если стабильность основного (базового) обмена не меняется в течение суток, то скорость факультативных энергозатратных процессов значительно повышается в дневное время и снижается в ночные часы.Эндогенное образование катионов водорода (Н+) сопровождает все реакции трансформации аденозинтрифосфата. Так, гликолиз сопровождается лактоацидозом цитоплазмы, а цикл трикарбоновых кислот вовсе выполняет водорододонорную функцию, поставляя в дыхательную цепь митохондрии Н+. При этом, в зависимости от скорости окислительного фосфорилирования, определенная часть Н+ выводится в межклеточное пространство, откуда в дальнейшем попадает в слюну и мочу. Суточные осцилляции рН и Еh в моче и ротовой жидкости (слюне) здоровых людей отражают циркадную ритмичность метаболических процессов и могут явиться важными показателями нарушения обмена веществ при распространенных заболеваниях, сопровождающихся нарушением энергетического метаболизма.

Urine and saliva are the most accessible liquids for studying circadian oscillations coherent with the activity of ongoing metabolic processes, which are characterized by a change in the rate and direction of the formation of protons (H+) and electrons (ē). The existing balance of acid-base state (pH) and redox potential (Eh) is an important indicator of homeostasis, reflecting the state of energy metabolism, i.e., the process of dissimilation. If the stability of the main (basic) metabolism does not change during the day, then the rate of facultative energy-consuming processes increases significantly during the daytime and decreases at night.Endogenous formation of hydrogen cations (H+) accompanies all transformation reactions of adenosine triphosphate. Thus, glycolysis is accompanied by lactic acidosis of the cytoplasm, and the tricarboxylic acid cycle performs a hydrogen-donor function, supplying protons (H+) to the respiratory chain of mitochondria. At the same time, depending on the rate of oxidative phosphorylation, a certain part of hydrogen cations (H+) is excreted into the intercellular space, from where it subsequently enters saliva and urine.Daily oscillations of pH and Eh in the urine and oral fluid (saliva) of healthy people reflect the circadian rhythm of metabolic processes and can be important indicators of metabolic disorders in common diseases accompanied by impaired energy metabolism.

энергетический метаболизмкислотно-основное состояниеокислительно-восстановительный потенциалциркадная ритмичностьосциляции мочи и слюныenergy metabolismacid-base stateredox potentialcircadian rhythmurine and saliva oscillationsReferencesSchmitt EE, Johnson EK, Yusifova M, et al. The renal molecular clock: broken by aging and restored by exercise. Am J Physiol Renal Physiol. 2019;317(5):F1087–F1093. PMID: 31461350. PMCID: PMC6879930. https://doi.org/10.1152/ajprenal.00301.2019Schmitt EE, Johnson EK, Yusifova M, et al. The renal molecular clock: broken by aging and restored by exercise. Am J Physiol Renal Physiol. 2019;317(5):F1087–F1093. PMID: 31461350. PMCID: PMC6879930. https://doi.org/10.1152/ajprenal.00301.2019Chacko BK, Kramer PA, Ravi S, et al. Bioenergetic health index: a new concept in mitochondrial translational research. Clin Sci (Lond). 2014;127:367–373. PMID: 24895057. PMCID: PMC4202728. https://doi.org/10.1042/cs20140101Chacko BK, Kramer PA, Ravi S, et al. Bioenergetic health index: a new concept in mitochondrial translational research. Clin Sci (Lond). 2014;127:367–373. PMID: 24895057. PMCID: PMC4202728. https://doi.org/10.1042/cs20140101Brunner M, Schafmeier T. Transcriptional and post-transcriptional regulation of the circadian clock in cyanobacteria and neurospora. Gene Dev. 2006;20(9):1061–1074. PMID: 16651653. https://doi.org/10.1101/gad.1410406Brunner M, Schafmeier T. Transcriptional and post-transcriptional regulation of the circadian clock in cyanobacteria and neurospora. Gene Dev. 2006;20(9):1061–1074. PMID: 16651653. https://doi.org/10.1101/gad.1410406Harmer SL. The circadian system in higher plants. Annual Review of Plant Biology. 2009;60:357–377. PMID: 19575587. https://doi.org/10.1146/annurev.arplant.043008.092054Harmer SL. The circadian system in higher plants. Annual Review of Plant Biology. 2009;60:357–377. PMID: 19575587. https://doi.org/10.1146/annurev.arplant.043008.092054Rosato E, Tauber E, Kyriacou CP. Molecular genetics of the fruit fly circadian clock. Eur J Hum Genet. 2006;14(6):729–738. PMID: 16721409. https://doi.org/10.1038/sj.ejhg.5201547Rosato E, Tauber E, Kyriacou CP. Molecular genetics of the fruit fly circadian clock. Eur J Hum Genet. 2006;14(6):729–738. PMID: 16721409. https://doi.org/10.1038/sj.ejhg.5201547Mehra A, Baker SL, Loros JJ, et al. Post-translational modifications of circadian rhythms. Trends in biochemical sciences. 2009;34:483–490. PMID: 19740663. PMCID: PMC2765057. https://doi.org/10.1016/j.tibs.2009.06.006Mehra A, Baker SL, Loros JJ, et al. Post-translational modifications of circadian rhythms. Trends in biochemical sciences. 2009;34:483–490. PMID: 19740663. PMCID: PMC2765057. https://doi.org/10.1016/j.tibs.2009.06.006Cermakian N, Boivin DB. The regulation of central and peripheral circadian clocks in humans. Obes Rev. 2009;10(2):25–36. PMID: 19849799. https://doi.org/10.1111/j.1467-789x.2009.00660.xCermakian N, Boivin DB. The regulation of central and peripheral circadian clocks in humans. Obes Rev. 2009;10(2):25–36. PMID: 19849799. https://doi.org/10.1111/j.1467-789x.2009.00660.xFirsov D, Bonnie O. Circadian regulation of renal function. Kidney Int. 2010;78(7):640–645. PMID: 20664559. https://doi.org/10.1038/ki.2010.227Firsov D, Bonnie O. Circadian regulation of renal function. Kidney Int. 2010;78(7):640–645. PMID: 20664559. https://doi.org/10.1038/ki.2010.227Rosenfeld L. Henry Bence Jones (1813–1873): the best “chemical doctor” in London. Clinic Chem. 1987;33:1687–1692. PMID: 3304718.Rosenfeld L. Henry Bence Jones (1813–1873): the best “chemical doctor” in London. Clinic Chem. 1987;33:1687–1692. PMID: 3304718.Moore-Ede MC. Physiology of the circadian timing system: predictive versus reactive homeostasis. Am J Physiol. 1986;250:R737–752. PMID: 3706563. https://doi.org/10.1152/ajpregu.1986.250.5.r737Moore-Ede MC. Physiology of the circadian timing system: predictive versus reactive homeostasis. Am J Physiol. 1986;250:R737–752. PMID: 3706563. https://doi.org/10.1152/ajpregu.1986.250.5.r737Ayres JW, Weidler DJ, MacKichan J, et al. Circadian rhythm of urinary pH in man with and without chronic antacid administration. Eur J Clinic Pharmacol. 1977;12:415–420. PMID: 23296. https://doi.org/10.1007/bf00561060Ayres JW, Weidler DJ, MacKichan J, et al. Circadian rhythm of urinary pH in man with and without chronic antacid administration. Eur J Clinic Pharmacol. 1977;12:415–420. PMID: 23296. https://doi.org/10.1007/bf00561060Kanabrocki EL, Snedeker PW, Zieher SJ, et al. Circadian characteristics of dialyzable and non-dialyzable human urinary electrolytes, trace elements and total solids. Chronobiol Int. 1988;5:175–184. PMID: 3401983. https://doi.org/10.3109/07420528809079558Kanabrocki EL, Snedeker PW, Zieher SJ, et al. Circadian characteristics of dialyzable and non-dialyzable human urinary electrolytes, trace elements and total solids. Chronobiol Int. 1988;5:175–184. PMID: 3401983. https://doi.org/10.3109/07420528809079558Niv Y. Pentagastrin-induced alkaline flushing of urine is a recurring phenomenon that resolves after vagotomy. Israel Journal of Medical Sciences. 1992;28:97–98.Niv Y. Pentagastrin-induced alkaline flushing of urine is a recurring phenomenon that resolves after vagotomy. Israel Journal of Medical Sciences. 1992;28:97–98.Pizzorno J. Acidosis: An Old Idea Validated by New Research. Integr Med (Encinitas). 2015;14(1):8–12. PMID: 26770125. PMCID: PMC4566456.Pizzorno J. Acidosis: An Old Idea Validated by New Research. Integr Med (Encinitas). 2015;14(1):8–12. PMID: 26770125. PMCID: PMC4566456.Cameron M, Maalouf NM, Poindexter J, et al. The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers. Kidney Int. 2012;81(11):1123–1130. PMID: 22297671. PMCID: PMC3352978. https://doi.org/10.1038/ki.2011.480Cameron M, Maalouf NM, Poindexter J, et al. The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers. Kidney Int. 2012;81(11):1123–1130. PMID: 22297671. PMCID: PMC3352978. https://doi.org/10.1038/ki.2011.480Suter DM, Schibler U. Physiology. Feeding the clock. Science. 2009;326(5951):378–379. PMID: 19833950. https://doi.org/10.1126/science.1181278Suter DM, Schibler U. Physiology. Feeding the clock. Science. 2009;326(5951):378–379. PMID: 19833950. https://doi.org/10.1126/science.1181278Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–185. PMID: 28179656. https://doi.org/10.1038/nature21363Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–185. PMID: 28179656. https://doi.org/10.1038/nature21363Gamble KL, Young ME. Metabolism as an integral cog in the mammalian circadian clockwork. Crit Rev Biochem Mol Biol. 2013;48(4):317–331. PMID: 23594144. PMCID: PMC3862897. https://doi.org/10.3109/10409238.2013.786672Gamble KL, Young ME. Metabolism as an integral cog in the mammalian circadian clockwork. Crit Rev Biochem Mol Biol. 2013;48(4):317–331. PMID: 23594144. PMCID: PMC3862897. https://doi.org/10.3109/10409238.2013.786672Aguilar-López BA, Moreno-Altamirano MMB, Dockrell HM, et al. Mitochondria: An Integrative Hub Coordinating Circadian Rhythms, Metabolism, the Microbiome, and Immunity. Front Cell Dev Biol. 2020;8:51. PMID: 32117978. PMCID: PMC7025554. https://doi.org/10.3389/fcell.2020.00051Aguilar-López BA, Moreno-Altamirano MMB, Dockrell HM, et al. Mitochondria: An Integrative Hub Coordinating Circadian Rhythms, Metabolism, the Microbiome, and Immunity. Front Cell Dev Biol. 2020;8:51. PMID: 32117978. PMCID: PMC7025554. https://doi.org/10.3389/fcell.2020.00051Schmitt K, Grimm A, Dallmann R, et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metabolism; 2018;27(3):657–666. PMID: 29478834. https://doi.org/10.1016/j.cmet.2018.01.011Schmitt K, Grimm A, Dallmann R, et al. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metabolism; 2018;27(3):657–666. PMID: 29478834. https://doi.org/10.1016/j.cmet.2018.01.011Dennis SC, Gevers W, Opie LH. Protons in ischemia: where do they come from; where do they go to? J Mol Cell Cardiol. 1991;23(9):1077–1186. PMID: 1658348. https://doi.org/10.1016/0022-2828(91)91642-5Dennis SC, Gevers W, Opie LH. Protons in ischemia: where do they come from; where do they go to? J Mol Cell Cardiol. 1991;23(9):1077–1186. PMID: 1658348. https://doi.org/10.1016/0022-2828(91)91642-5Gillies R, Pilot C, Marunaka Y, et al. Targeting acidity in cancer and diabetes. Biochim Biophys Acta Rev Cancer. 2019;1871(2):273–280. PMID: 30708040. PMCID: PMC6525044. https://doi.org/10.1016/j.bbcan.2019.01.003Gillies R, Pilot C, Marunaka Y, et al. Targeting acidity in cancer and diabetes. Biochim Biophys Acta Rev Cancer. 2019;1871(2):273–280. PMID: 30708040. PMCID: PMC6525044. https://doi.org/10.1016/j.bbcan.2019.01.003Forney LG, McKinnon W, Lord GA, et al. Circulating anions commonly associated with the Krebs cycle in patients with metabolic acidosis. Crit Care. 2005;9(5):R591–595. https://doi.org/10.1186/cc3806Forney LG, McKinnon W, Lord GA, et al. Circulating anions commonly associated with the Krebs cycle in patients with metabolic acidosis. Crit Care. 2005;9(5):R591–595. https://doi.org/10.1186/cc3806Marunaka Y. The proposal of molecular mechanisms of weak organic acids intake-induced improvement of insulin resistance in diabetes mellitus via elevation of interstitial fluid pH. Int J Mol Sci. 2018;19(10):3244. PMID: 30347717. PMCID: PMC6214001. https://doi.org/10.3390/ijms19103244Marunaka Y. The proposal of molecular mechanisms of weak organic acids intake-induced improvement of insulin resistance in diabetes mellitus via elevation of interstitial fluid pH. Int J Mol Sci. 2018;19(10):3244. PMID: 30347717. PMCID: PMC6214001. https://doi.org/10.3390/ijms19103244Reinke H, Asher G. Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol. 2019;20(4):227–241. PMID: 30635659. https://doi.org/10.1038/s41580-018-0096-9Reinke H, Asher G. Crosstalk between metabolism and circadian clocks. Nat Rev Mol Cell Biol. 2019;20(4):227–241. PMID: 30635659. https://doi.org/10.1038/s41580-018-0096-9Scrima R, Cela O, Merla G, et al. Clock-genes and mitochondrial respiratory activity: evidence of a reciprocal interplay. Biochim Biophys Acta. 2016;1857(8):1344–1351. PMID: 27060253. https://doi.org/10.1016/j.bbabio.2016.03.035Scrima R, Cela O, Merla G, et al. Clock-genes and mitochondrial respiratory activity: evidence of a reciprocal interplay. Biochim Biophys Acta. 2016;1857(8):1344–1351. PMID: 27060253. https://doi.org/10.1016/j.bbabio.2016.03.035de Goede P, Wefers J, Brombacher EC, et al. Circadian rhythms in mitochondrial respiration. J Mol Endocrinol. 2018;60(3):R115–R130. PMID: 29378772. PMCID: PMC5854864. https://doi.org/10.1530/jme-17-0196de Goede P, Wefers J, Brombacher EC, et al. Circadian rhythms in mitochondrial respiration. J Mol Endocrinol. 2018;60(3):R115–R130. PMID: 29378772. PMCID: PMC5854864. https://doi.org/10.1530/jme-17-0196Ezagouri S, Asher G. Circadian control of mitochondrial dynamics and functions. Current Opinion in Physiology. 2018;5:25–29. https://doi.org/10.1016/j.cophys.2018.05.008Ezagouri S, Asher G. Circadian control of mitochondrial dynamics and functions. Current Opinion in Physiology. 2018;5:25–29. https://doi.org/10.1016/j.cophys.2018.05.008Berend K. Review of the diagnostic evaluation of normal anion gap metabolic acidosis. Kidney Dis (Basel). 2017;3(4):149–159. PMID: 29344509. PMCID:PMC5757610. https://doi.org/10.1159/000479279Berend K. Review of the diagnostic evaluation of normal anion gap metabolic acidosis. Kidney Dis (Basel). 2017;3(4):149–159. PMID: 29344509. PMCID:PMC5757610. https://doi.org/10.1159/000479279Mezhnina V, Ebigbe OP, Po A, et al. Circadian control of mitochondria in reactive oxygen species homeostasis. Antioxid Redox Signal. 2022. PMID: 35072523. https://doi.org/10.1089/ars.2021.0274Mezhnina V, Ebigbe OP, Po A, et al. Circadian control of mitochondria in reactive oxygen species homeostasis. Antioxid Redox Signal. 2022. PMID: 35072523. https://doi.org/10.1089/ars.2021.0274Manoogian ENC, Satchidananda P. Circadian clock, nutrient quality, and eating pattern tune diurnal rhythms in the mitochondrial proteome. Proceedings of the National Academy of Sciences. 2016;113(12);3127–3129. https://doi.org/10.1073/pnas.1601786113Manoogian ENC, Satchidananda P. Circadian clock, nutrient quality, and eating pattern tune diurnal rhythms in the mitochondrial proteome. Proceedings of the National Academy of Sciences. 2016;113(12);3127–3129. https://doi.org/10.1073/pnas.1601786113Cupisti A, D’Alessandro C. Metabolic and dietary features in kidney stone formers: nutritional approach. J Bras Nefrol. 2020;42(3):271–272. PMID: 32495817. PMCID: PMC7657041. https://doi.org/10.1590/2175-8239-jbn-2020-0061Cupisti A, D’Alessandro C. Metabolic and dietary features in kidney stone formers: nutritional approach. J Bras Nefrol. 2020;42(3):271–272. PMID: 32495817. PMCID: PMC7657041. https://doi.org/10.1590/2175-8239-jbn-2020-0061Опарин А., Фесенков В. Жизнь во Вселенной. М.: издательство Академии наук СССР, 3-е издание, 1956, 228 с.Oparin A., Fesenkov V. Life in the Universe. M.: Publishing House of the USSR Academy of Science, 3rd edition, 1956, 228 p.

The authors declare that there are no conflicts of interest present.