Chen H M, Lin W W, Ferguson K H, Scott B K, Peterson C M
Sansum Medical Research Foundation, Santa Barbara, CA 93105.
Alcohol Clin Exp Res. 1994 Oct;18(5):1202-6. doi: 10.1111/j.1530-0277.1994.tb00105.x.
We noted a rise in acetaldehyde levels in clinical samples of venous whole blood containing ethanol that did not occur in samples from teetotalers. Experiments were performed to define the mechanism involved in acetaldehyde production. The addition of 0.10% ethanol to whole blood produced an immediate increase in acetaldehyde due to acetaldehyde in the stock solution followed by a subsequent increase that became statistically significant by 48 hr. Separation of blood into components documented that the increase in acetaldehyde was associated with the red cell but not plasma fraction. Incubation of isolated hemoglobin with ethanol produced a rise in acetaldehyde levels. Incubation of oxygenated whole blood with ethanol produced a linear increase in acetaldehyde, whereas nitrogen-exposed blood produced no increase. The rise of acetaldehyde in the presence of ethanol was dependent on the concentration of oxygenated hemoglobin A0. Addition of inhibitors of catalase, alcohol dehydrogenase, and glycolytic enzymes (aminotriazole, azide, pyrazole, sodium fluoride, sodium citrate, and iodoacetate) did not inhibit the rise of acetaldehyde, but addition of the hemoglobin ligand cyanide abolished the rise in acetaldehyde. Kinetic analysis with oxygenated whole blood plus inhibitors revealed a Km of 2.5 mM and Vmax of 1.42 microM/min. We conclude that oxyhemoglobin contributes to the metabolism of ethanol to acetaldehyde. These findings may explain in part the high levels of acetaldehyde found in red cells compared with plasma. The results also have implications for the optimum storage of blood samples for acetaldehyde analysis.
我们注意到，含乙醇的静脉全血临床样本中的乙醛水平有所上升，而在戒酒者的样本中未出现这种情况。我们进行了实验以确定乙醛产生所涉及的机制。向全血中添加0.10%的乙醇会使乙醛立即增加，这是由于储备溶液中的乙醛所致，随后会进一步增加，到48小时时具有统计学意义。将血液分离成不同成分表明，乙醛的增加与红细胞有关，而与血浆部分无关。将分离出的血红蛋白与乙醇一起孵育会使乙醛水平升高。将含氧全血与乙醇一起孵育会使乙醛呈线性增加，而暴露于氮气中的血液则不会增加。在乙醇存在的情况下，乙醛的增加取决于氧合血红蛋白A0的浓度。添加过氧化氢酶、乙醇脱氢酶和糖酵解酶的抑制剂（氨基三唑、叠氮化物、吡唑、氟化钠、柠檬酸钠和碘乙酸盐）并不能抑制乙醛的增加，但添加血红蛋白配体氰化物可消除乙醛的增加。对含氧全血加抑制剂进行动力学分析显示，Km为2.5 mM，Vmax为1.42 microM/分钟。我们得出结论，氧合血红蛋白有助于将乙醇代谢为乙醛。这些发现可能部分解释了与血浆相比红细胞中乙醛水平较高的原因。这些结果对于用于乙醛分析的血液样本的最佳储存也具有启示意义。
