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Among them are DNA, RNA, enzymes, and coenzymes. All the DNA is doubled during each S (synthesis) cell cycle phase. This means that six billion nucleic acids must be synthesized in each cycle. Tumor growth, proliferation, and mutations all depend on this synthesis. Cancer cells require a constant supply of nucleotides and other macromolecules. For this reason, they must stimulate de novo nucleotide synthesis to support nucleic acid provision. When deregulated, de novo nucleic acid synthesis is controlled by oncogenes and tumor suppressor genes that enable increased synthesis and cell proliferation. Furthermore, cell duplication must be achieved swiftly (in a few hours) and in the midst of a nutrient-depleted and hypoxic environment. This also means that the enzymes participating in nucleic acid synthesis must work efficiently. pH is a critical factor in enzymatic efficiency and speed. This review will show that the enzymatic machinery working in nucleic acid synthesis requires a pH on the alkaline side in most cases. This coincides with many other pro-tumoral factors, such as the glycolytic phenotype, benefiting from an increased intracellular pH. An increased intracellular pH is a perfect milieu for high de novo nucleic acid production through optimal enzymatic performance.<\/jats:p>","DOI":"10.3390\/jox12030014","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T09:41:10Z","timestamp":1657100470000},"page":"158-180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Role of pH in Regulating Cancer Pyrimidine Synthesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-9095","authenticated-orcid":false,"given":"Saad Saeed","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"},{"name":"Pharmacy Practice Research Unit, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}]},{"given":"Tomas","family":"Koltai","sequence":"additional","affiliation":[{"name":"Via Pier Capponi 6, 50132 Florence, Italy"}]},{"given":"Muntaser E.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan"}]},{"given":"Adil H. H.","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan"}]},{"given":"Sari T. S.","family":"Alhoufie","sequence":"additional","affiliation":[{"name":"Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, Medina 42353, Saudi Arabia"}]},{"given":"Samrein B. M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Chemistry, College of Health, Wellbeing and Life Sciences, Sheffield Hallam University, Sheffield S1 1WB, UK"}]},{"given":"Daria Di","family":"Molfetta","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-1413","authenticated-orcid":false,"given":"Tiago M. A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-9135","authenticated-orcid":false,"given":"Rosa Angela","family":"Cardone","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9757-5908","authenticated-orcid":false,"given":"Stephan Joel","family":"Reshkin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy"}]},{"given":"Abdelhameed","family":"Hifny","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Al-Azhar University, Cairo 11651, Egypt"}]},{"given":"Mohamed E.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Research Center, Zamzam University College, Khartoum 11123, Sudan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-6117","authenticated-orcid":false,"given":"Khalid Omer","family":"Alfarouk","sequence":"additional","affiliation":[{"name":"Research Center, Zamzam University College, Khartoum 11123, Sudan"},{"name":"Alfarouk Biomedical Research LLC, Temple Terrace, FL 33617, USA"},{"name":"Hala Alfarouk Cancer Center, Khartoum 11123, Sudan"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/cber.19090420105","article-title":"\u00dcber den jetzigen Stand der Chemotherapie","volume":"42","author":"Ehrlich","year":"1909","journal-title":"Ber. 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