Pyridoxal 5'-phosphate is a selective inhibitor in vivo of DNA polymerase alpha and epsilon.
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.
Mizushina
Yoshiyuki
Y
Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, 651-2180, Hyogo, Japan. mizushin@nutr.kobegakuin.ac.jp
Xu
Xianai
X
Matsubara
Kiminori
K
Murakami
Chikako
C
Kuriyama
Isoko
I
Oshige
Masahiko
M
Takemura
Masaharu
M
Kato
Norihisa
N
Yoshida
Hiromi
H
Sakaguchi
Kengo
K
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
D004791:Enzyme Inhibitors; D011730:Pyridoxal; D011732:Pyridoxal Phosphate; D004256:DNA Polymerase I; D004257:DNA Polymerase II