Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Roma, Italy.
Microbiology (Reading). 2023 Apr;169(4). doi: 10.1099/mic.0.001319.
Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B and a cofactor for many essential metabolic processes such as amino acid biosynthesis and one carbon metabolism. 4'-deoxypyridoxine (4dPN) is a long known B antimetabolite but its mechanism of action was not totally clear. By exploring different conditions in which PLP metabolism is affected in the model organism K12, we showed that 4dPN cannot be used as a source of vitamin B as previously claimed and that it is toxic in several conditions where vitamin B homeostasis is affected, such as in a B auxotroph or in a mutant lacking the recently discovered PLP homeostasis gene, . In addition, we found that 4dPN sensitivity is likely the result of multiple modes of toxicity, including inhibition of PLP-dependent enzyme activity by 4'-deoxypyridoxine phosphate (4dPNP) and inhibition of cumulative pyridoxine (PN) uptake. These toxicities are largely dependent on the phosphorylation of 4dPN by pyridoxal kinase (PdxK).
吡哆醛 5'-磷酸（PLP）是维生素 B 的活性形式，也是许多重要代谢过程的辅助因子，如氨基酸生物合成和一碳代谢。4'-脱氧吡哆醇（4dPN）是一种长期已知的 B 抗代谢物，但它的作用机制尚不完全清楚。通过在模式生物 K12 中探索影响 PLP 代谢的不同条件，我们表明 4dPN 不能像以前声称的那样用作维生素 B 的来源，并且在维生素 B 稳态受到影响的几种情况下，如 B 营养缺陷型或缺乏最近发现的 PLP 稳态基因的突变体，它是有毒的。此外，我们发现 4dPN 敏感性可能是多种毒性模式的结果，包括 4'-脱氧吡啶酮磷酸盐（4dPNP）抑制 PLP 依赖性酶活性和抑制累积吡哆醇（PN）摄取。这些毒性在很大程度上取决于吡哆醛激酶（PdxK）对 4dPN 的磷酸化。
