title: Pyridoxal 5'-phosphate is a selective inhibitor in vivo of DNA polymerase alpha and epsilon.
abstract: Vitamin B(6) compounds such as pyridoxal 5(')-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and pyridoxamine (PM), which reportedly have anti-angiogenic and anti-cancer effects, were thought to be inhibitors of some types of eukaryotic DNA polymerases. PL moderately inhibited only the activities of calf DNA polymerase alpha (pol alpha), while PN and PM had no inhibitory effects on any of the polymerases tested. On the other hand, PLP, a phosphated form of PL, was potentially a strong inhibitor of pol alpha and epsilon from phylogenetic-wide organisms including mammals, fish, insects, plants, and protists. PLP did not suppress the activities of prokaryotic DNA polymerases such as Escherichia coli DNA polymerase I and Taq DNA polymerase, or DNA-metabolic enzymes such as deoxyribonuclease I. For pol alpha and epsilon, PLP acted non-competitively with the DNA template-primer and competitively with the nucleotide substrate. Since PL was converted to PLP in vivo after being incorporated into human cancer cells, the anti-angiogenic and anti-cancer effects caused by PL must have been caused by the inhibition of pol alpha and epsilon activities after conversion to PLP.
authors.affiliation: Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, 651-2180, Hyogo, Japan. mizushin@nutr.kobegakuin.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Xianai
authors.initials: X
authors.lastname: Xu
authors.forename: Kiminori
authors.initials: K
authors.lastname: Matsubara
authors.forename: Chikako
authors.initials: C
authors.lastname: Murakami
authors.forename: Isoko
authors.initials: I
authors.lastname: Kuriyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Oshige
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takemura
authors.forename: Norihisa
authors.initials: N
authors.lastname: Kato
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: D002470:Cell Survival / Q000187:drug effects*; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D006367:HeLa Cells; D006801:Humans; D011730:Pyridoxal / Q000737:chemistry / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000737:chemistry* / Q000494:pharmacology*; D012680:Sensitivity and Specificity
chemical_list: D004791:Enzyme Inhibitors; D011730:Pyridoxal; D011732:Pyridoxal Phosphate; D004256:DNA Polymerase I; D004257:DNA Polymerase II