Lindahl R
Biochem J. 1979 Oct 1;183(1):55-64. doi: 10.1042/bj1830055.
The subcellular distribution and properties of four aldehyde dehydrogenase isoenzymes (I-IV) identified in 2-acetylaminofluorene-induced rat hepatomas and three aldehyde dehydrogenases (I-III) identified in normal rat liver are compared. In normal liver, mitochondria (50%) and microsomal fraction (27%) possess the majority of the aldehyde dehydrogenase, with cytosol possessing little, if any, activity. Isoenzymes I-III can be identified in both fractions and differ from each other on the basis of substrate and coenzyme specificity, substrate K(m), inhibition by disulfiram and anti-(hepatoma aldehyde dehydrogenase) sera, and/or isoelectric point. Hepatomas possess considerable cytosolic aldehyde dehydrogenase (20%), in addition to mitochondrial (23%) and microsomal (35%) activity. Although isoenzymes I-III are present in tumour mitochondrial and microsomal fractions, little isoenzyme I or II is found in cytosol. Of hepatoma cytosolic aldehyde dehydrogenase activity, 50% is a hepatoma-specific isoenzyme (IV), differing in several properties from isoenzymes I-III; the remainder of the tumour cytosolic activity is due to isoenzyme III (48%). The data indicate that the tumour-specific aldehyde dehydrogenase phenotype is explainable by qualitative and quantitative changes involving primarily cytosolic and microsomal aldehyde dehydrogenase. The qualitative change requires the derepression of a gene for an aldehyde dehydrogenase expressed in normal liver only after exposure to potentially harmful xenobiotics. The quantitative change involves both an increase in activity and a change in subcellular location of a basal normal-liver aldehyde dehydrogenase isoenzyme.
对在2-乙酰氨基芴诱导的大鼠肝癌中鉴定出的四种醛脱氢酶同工酶（I-IV）和在正常大鼠肝脏中鉴定出的三种醛脱氢酶（I-III）的亚细胞分布及特性进行了比较。在正常肝脏中，线粒体（50%）和微粒体部分（27%）含有大部分醛脱氢酶，而胞质溶胶中即使有活性也很少。同工酶I-III可在这两个部分中鉴定出来，它们在底物和辅酶特异性、底物K(m)、双硫仑和抗（肝癌醛脱氢酶）血清的抑制作用以及/或等电点方面彼此不同。肝癌除了具有线粒体（23%）和微粒体（35%）活性外，还具有相当数量的胞质醛脱氢酶（20%）。虽然同工酶I-III存在于肿瘤线粒体和微粒体部分，但在胞质溶胶中很少发现同工酶I或II。肝癌胞质醛脱氢酶活性的50%是一种肝癌特异性同工酶（IV），其在几个特性上与同工酶I-III不同；肿瘤胞质活性的其余部分归因于同工酶III（48%）。数据表明，肿瘤特异性醛脱氢酶表型可通过主要涉及胞质和微粒体醛脱氢酶的定性和定量变化来解释。定性变化需要解除对一种仅在接触潜在有害的外源化学物质后才在正常肝脏中表达的醛脱氢酶基因的抑制。定量变化既涉及活性增加，也涉及基础正常肝脏醛脱氢酶同工酶的亚细胞定位变化。
