HUMAN LIVER FATTY ALDEHYDE DEHYDROGENASE - MICROSOMAL LOCALIZATION, PURIFICATION, AND BIOCHEMICAL-CHARACTERIZATION

To better understand the genetic disorder Sjogren-Larsson syndrome whi ch is caused by a deficiency of fatty aldehyde dehydrogenase activity, we determined the subcellular localization of the enzyme and investig ated its biochemical properties. Using density gradient centrifugation , we found that fatty aldehyde dehydrogenase activity was predominantl y localized in the microsomal fraction in human liver. This fatty alde hyde dehydrogenase was solubilized from human liver microsomes and pur ified by chromatography on columns consisting of omega-aminohexyl-agar ose and 5'-AMP-Sepharose 4B. The enzyme had an apparent subunit molecu lar weight of 54000, required NAD(+) as cofactor, had optimal activity at pH 9.8, and was thermolabile at 47 degrees C. Fatty aldehyde dehyd rogenase had high activity towards saturated and unsaturated aliphatic aldehydes ranging from 6 to 24 carbons in length, as well as dihydrop hytal, a 20-carbon branched chain aldehyde. In contrast, acetaldehyde, propionaldehyde, crotonaldehyde, glutaraldehyde, benzaldehyde, and re tinaldehyde were poor substrates. The enzyme was inhibited by disulfir am, iodoacetamide, alpha,p-dibromoacetophenone, and p-chloromercuriben zoate. These results indicate that microsomal fatty aldehyde dehydroge nase is a distinct human aldehyde dehydrogenase isozyme that acts on a variety of medium- and long-chain aliphatic substrates.