Casanova-Schmitz M, David R M, Heck H D
Biochem Pharmacol. 1984 Apr 1;33(7):1137-42. doi: 10.1016/0006-2952(84)90526-4.
Homogenates of respiratory and olfactory tissue from the rat nasal cavity were examined for their capacity to catalyze the NAD+-dependent oxidation of formaldehyde (in the presence and absence of glutathione) and of acetaldehyde. Both aldehydes were oxidized efficiently by nasal mucosal homogenates, and formaldehyde dehydrogenase (FDH) and aldehyde dehydrogenase (AldDH) were tentatively identified in both tissue samples. At least two isozymes of AldDH, differing with respect to their apparent Km and Vmax values with acetaldehyde as substrate, were found in the nasal mucosa, one of which may catalyze the oxidation of both formaldehyde and acetaldehyde. The specific activity of FDH in the olfactory mucosa was twice that in the respiratory mucosa, whereas the specific activity of the higher Km isozyme of AldDH was five to eight times greater in respiratory than in olfactory tissue. The specific activity of the lower Km isozyme of AldDH was similar in respiratory and olfactory homogenates. Repeated exposures of rats to formaldehyde (15 ppm, 6 hr/day, 10 days) or to acetaldehyde (1500 ppm, 6hr/day, 5 days) did not substantially affect the specific activities of FDH and AldDH in nasal mucosal homogenates. Glutathione is a cofactor for FDH; the concentration of nonprotein sulfhydryls in respiratory mucosal homogenates was approximately 2.8 mumoles/g and was not changed significantly by repeated exposures to formaldehyde (15 ppm, 6hr/day, 9 days). These data indicate that the rat nasal mucosa, which is the major target site for both aldehydes in inhalation toxicity studies, can metabolize both formaldehyde and acetaldehyde, and that the specific activities of formaldehyde and aldehyde dehydrogenase in homogenates of the nasal mucosa are essentially unchanged following repeated exposures to toxic concentrations of either compound.
对大鼠鼻腔呼吸组织和嗅觉组织的匀浆进行检测，以考察它们催化NAD⁺依赖性甲醛（存在和不存在谷胱甘肽的情况下）及乙醛氧化的能力。两种醛均可被鼻黏膜匀浆有效氧化，并且在两个组织样本中初步鉴定出甲醛脱氢酶（FDH）和乙醛脱氢酶（AldDH）。在鼻黏膜中发现至少两种AldDH同工酶，它们以乙醛为底物时的表观Km值和Vmax值不同，其中一种可能催化甲醛和乙醛的氧化。嗅觉黏膜中FDH的比活性是呼吸黏膜中的两倍，而AldDH的较高Km同工酶在呼吸组织中的比活性比嗅觉组织中高五到八倍。AldDH的较低Km同工酶在呼吸和嗅觉匀浆中的比活性相似。大鼠反复暴露于甲醛（15 ppm，每天6小时，共10天）或乙醛（1500 ppm，每天6小时，共5天），并未显著影响鼻黏膜匀浆中FDH和AldDH的比活性。谷胱甘肽是FDH的辅因子；呼吸黏膜匀浆中非蛋白巯基的浓度约为2.8微摩尔/克，反复暴露于甲醛（15 ppm，每天6小时，共9天）后未发生显著变化。这些数据表明，在吸入毒性研究中作为两种醛主要靶位点的大鼠鼻黏膜能够代谢甲醛和乙醛，并且在反复暴露于任一化合物的毒性浓度后，鼻黏膜匀浆中甲醛脱氢酶和乙醛脱氢酶的比活性基本未变。
