{"id":15753,"date":"2022-06-24T13:51:06","date_gmt":"2022-06-24T06:51:06","guid":{"rendered":"https:\/\/bgrssb.icgbio.ru\/2022\/?p=15753"},"modified":"2022-09-20T10:32:31","modified_gmt":"2022-09-20T03:32:31","slug":"impact-of-negative-feedbacks-on-de-novo-pyrimidines-biosynthesis-in-e-coli","status":"publish","type":"post","link":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/2022\/06\/24\/impact-of-negative-feedbacks-on-de-novo-pyrimidines-biosynthesis-in-e-coli\/","title":{"rendered":"Impact of negative feedbacks on de novo pyrimidines biosynthesis in E.coli"},"content":{"rendered":"<p><em>by Khlebodarova T.M. | Akberdin I.R. | Kozlov K.N. | Kazantsev F.V. | Fadeev S.I. | Likhoshvai V.A. |<\/em><br \/>\n<em>Institute Cytology and Genetics SB RAS | Department of Systems Biology, Institute of Cytology and<\/em><br \/>\n<em>Genetics SB RAS, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University,<\/em><br \/>\n<em>Novosibirsk, Russia; Department of Computational Biology, Sirius University of Science and Technology,<\/em><br \/>\n<em>Sochi, Russia; Biosoft.RU LTD, Novosibirsk, Russia. | 6Higher School for Applied Mathematics and<\/em><br \/>\n<em>Computational Physics, PhysMech, Peter the Great St. Petersburg Polytechnic University, St. Petersburg,<\/em><br \/>\n<em>Russia | Department of Systems Biology, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia;<\/em><br \/>\n<em>Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia | Institute of<\/em><br \/>\n<em>Mathematics SB RAS, Novosibirsk, Russia; Deceased | Department of Systems Biology, Institute of<\/em><br \/>\n<em>Cytology and Genetics SB RAS, Novosibirsk, Russia; Deceased<\/em><\/p>\n<p><strong>Background:<\/strong>\u00a0Previous studies aimed to investigate the metabolism of endogenous<br \/>\nnucleoside triphosphates in synchronous E. coli cell cultures demonstrated an existence of<br \/>\nthe self-oscillatory mode of the functioning of pyrimidines and purines biosynthesis. Authors<br \/>\nof these studies associated the dynamic behavior with cell division. The metabolic system<br \/>\ntheoretically has an internal oscillatory potential due to feedback mechanisms orchestrating<br \/>\nits dynamics. The question of whether the nucleotide biosynthesis system has its own<br \/>\noscillatory circuit is still open.<br \/>\n<strong>Results:<\/strong>\u00a0To solve this issue, an integral mathematical model of pyrimidine biosynthesis was<br \/>\ndeveloped, which explores all experimentally verified negative feedbacks in the regulation<br \/>\nof enzymatic reactions, data on detection under in vitro conditions. An analysis of the<br \/>\ndynamic modes of the model functioning showed the possibility of implementing both<br \/>\nstationary and oscillating modes of functioning in the pyrimidine biosynthesis system for<br \/>\ncertain sets of kinetic parameters that fit within the physiological boundaries of the<br \/>\nmetabolic system under study. It was shown that the occurrence of an oscillating nature of<br \/>\nthe synthesis of metabolites depended on the ratio of two parameters: the Hill coefficient,<br \/>\nwhich is the nonlinearity of the influence of UMP on the activity of carbamoylphosphate<br \/>\nsynthetase, and the parameter r, which characterizes the contribution of the noncompetitive<br \/>\nmechanism of UTP inhibition to the regulation of the enzymatic reaction of UMP<br \/>\nphosphorylation.<br \/>\n<strong>Conclusions:<\/strong> It was suggested that the system of pyrimidines biosynthesis in E. coli has its<br \/>\nown oscillatory mode the potential of that substantially depends on the mechanisms of UMP<br \/>\nkinase\u2019s activity.<\/p>\n<a href=\"https:\/\/bgrssb.icgbio.ru\/2022\/wp-content\/uploads\/sites\/3\/2022\/06\/Khlebodarova_Akberdin_BGRS_2022.pdf\" class=\"pdfemb-viewer\" style=\"\" data-width=\"max\" data-height=\"max\"  data-toolbar=\"bottom\" data-toolbar-fixed=\"off\">Khlebodarova_Akberdin_BGRS_2022<br\/><\/a>\n","protected":false},"excerpt":{"rendered":"<p>by Khlebodarova T.M. | Akberdin I.R. | Kozlov K.N. | Kazantsev F.V. | Fadeev S.I. | Likhoshvai V.A. | Institute Cytology and Genetics SB RAS | Department of Systems Biology, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia; Department of Computational Biology, Sirius University of [&hellip;]<\/p>\n","protected":false},"author":3967,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[6],"tags":[221,222,223,224],"_links":{"self":[{"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/posts\/15753"}],"collection":[{"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/users\/3967"}],"replies":[{"embeddable":true,"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/comments?post=15753"}],"version-history":[{"count":1,"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/posts\/15753\/revisions"}],"predecessor-version":[{"id":15755,"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/posts\/15753\/revisions\/15755"}],"wp:attachment":[{"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/media?parent=15753"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/categories?post=15753"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bgrssb.icgbio.ru\/2022\/ru\/wp-json\/wp\/v2\/tags?post=15753"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}