Mechanism of Swift lncrease in Alcohol Metabolism and Individual Difference of its metabolism

在医疗法律实践中对血液酒精浓度的估计中，乙醇消除能力的个体间和个体内的差异是一个重要的问题。反复饮酒引起的酶诱导是引起酒精代谢个体差异的著名机制之一。此外，短时间暴露产生的酒精代谢的加速增加，被称为SIAM(Swift Increase in Alcool Metoxism，瑟曼等人，1979)，被认为是另一种机制。在这种SIAM现象中，急性给予高浓度酒精会加速耗氧量和酒精代谢的增加。本研究的目的是探讨SIAM现象的发生机制，并了解SIAM现象与乙醇代谢个体差异的关系。此外，还详细研究了SIAM对乙醛和乙酸乙酯的处理效果。结果，获得了SIAM现象发生的条件和足够的重复性，并发现醋酸盐的血液浓度随着酒精清除率的加速增加而增加。这些结果表明，稳态血醋酸盐浓度可作为SIAM的一个指标。这种血醋酸酯的变化成为SIAM研究的新知识。将该实验条件和药代动力学数据用于生化研究。因此，乙醇脱氢酶和乙醛脱氢酶的含量在SIAM现象期间没有变化。然而，一些细胞色素的含量随着SIAM现象的变化而变化。进一步的研究正在进行中。

In the estimation of blood-alcohol-concentration performed in Medico-Legal practice, the inter- and intra-individual difference of ethanol elimination capacity is an important problem. The enzyme induction with repeated alcohol drinking is one of famous mechanisms to evoke an individual difference in alcohol metabolism. In addition, the accelerative increase of the alcohol metabolism produced for a short time exposure, called SIAM (Swift Increase in Alcohol Metabolism, Thurman and others, 1979), is thought to be another mechanism. In this SIAM phenomenon oxygen consumption and alcohol metabolism rise accelerative by acute administration of high-concentration alcohol. The purpose of this study is to examine the mechanism of SIAM phenomenon and to know the relationship between this SIAM phenomenon and individual difference of ethanol metabolism. Furthermore, the effects of SIAM to the disposition of acetaldehyde and acetate are studied in detail. As a result, the conditions which SIAM phenomenon occurs with sufficient reproducibility were acquired, and it was found that the blood concentration of acetate increases with accelerative increase of an alcoholic elimination rate. These results indicate that the steady-state concentration of blood acetate serves as an index of SIAM. This change of blood acetate became new knowledge for SIAM study. This experimental condition and pharmacokinetic data were used for biochemical studies. Consequently, contents of alcohol dehydrogenase and aldehyde dehydrogenase did not change during the SIAM phenomenon. However, content of some cytochrome change with SIAM phenomenon. Further study is being performed.