Orotate phosphoribosyltransferase from yeast: Studies of the structure of the pyrimidine substrate binding site

Ashton, Robert W.; Strauss, Rosalyn S.; Chung, Sung Hyun; Sloan, Donald L.

doi:10.1016/0003-9861(89)90236-1

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…The optimal pH of the OPRT for the forward reaction is 8, while for the reverse reaction it ranges between 6.5 and 7.5 [94]. The optimal pH of the OPRT for the forward reaction is 8, while for the reverse reaction it ranges between 6.5 and 7.5 [94].…”

Section: Dihydroorotase Inhibitorsmentioning

confidence: 98%

“…OPRT inhibition also plays a role in other diseases, e.g., tuberculosis, toxoplasmosis, and malaria [97]. The optimal pH of the OPRT for the forward reaction is 8, while for the revers tion it ranges between 6.5 and 7.5 [94].…”

Section: Dihydroorotase Inhibitorsmentioning

confidence: 99%

“…The optimal pH of the OPRT for the forward reaction is 8, while for the reverse reaction it ranges between 6.5 and 7.5 [ 94 ].…”

Section: The Pyrimidine Synthesis Pathwaymentioning

confidence: 99%

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Role of pH in Regulating Cancer Pyrimidine Synthesis

Al‐Qahtani

Koltai²,

Ibrahim

et al. 2022

JoX

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Replication is a fundamental aspect of cancer, and replication is about reproducing all the elements and structures that form a cell. 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.

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Section: Dihydroorotase Inhibitorsmentioning

confidence: 98%

Section: Dihydroorotase Inhibitorsmentioning

confidence: 99%