Aldehyde dehydrogenase class 3, encoded by ADH5 in humans, catalyzes the glutathione dependent detoxification of formaldehyde. Here we show that ADH5 deficient cells turn over formaldehyde using alternative pathways starting from the reaction of formaldehyde with free amino acids. When mammalian cells are exposed to formaldehyde, the levels of the reaction products of formaldehyde with the amino acids cysteine and histidine - timonacic and spinacine - are increased. These reactions take place spontaneously and the formation of timonacic is reversible. The levels of timonacic are higher in the plasma of Adh5^−/− mice relative to controls and they are further increased upon administration of methanol. We conclude that mammals possess pathways of cysteine and histidine dependent formaldehyde metabolism and that timonacic is a formaldehyde reservoir.

人体中由ADH5编码的第 3 类醛脱氢酶催化谷胱甘肽依赖性甲醛解毒。在这里，我们表明 ADH5 缺陷细胞使用从甲醛与游离氨基酸反应开始的替代途径来转化甲醛。当哺乳动物细胞暴露于甲醛时，甲醛与氨基酸半胱氨酸和组氨酸（timonacic 和 spinacine）的反应产物水平会增加。这些反应自发发生并且钛莫酸的形成是可逆的。Adh5血浆中的钛莫酸水平较高^-/-小鼠相对于对照组，并且在施用甲醇后进一步增加。我们得出结论，哺乳动物拥有依赖于半胱氨酸和组氨酸的甲醛代谢途径，并且噻莫那酸是甲醛储存库。