Publications

• Human liver fatty aldehyde dehydrogenase: microsomal localization, purification, and biochemical characterization.

  Kelson T.L., Secor McVoy J.R., Rizzo W.B.

  To better understand the genetic disorder Sjogren-Larsson syndrome which is caused by a deficiency of fatty aldehyde dehydrogenase activity, we determined the subcellular localization of the enzyme and investigated its biochemical properties. Using density gradient centrifugation, we found that fa ... >> More

  To better understand the genetic disorder Sjogren-Larsson syndrome which is caused by a deficiency of fatty aldehyde dehydrogenase activity, we determined the subcellular localization of the enzyme and investigated its biochemical properties. Using density gradient centrifugation, we found that fatty aldehyde dehydrogenase activity was predominantly localized in the microsomal fraction in human liver. This fatty aldehyde dehydrogenase was solubilized from human liver microsomes and purified by chromatography on columns consisting of omega-aminohexyl-agarose and 5'-AMP-Sepharose 4B. The enzyme had an apparent subunit molecular weight of 54000, required NAD+ as cofactor, had optimal activity at pH 9.8, and was thermolabile at 47 degrees C. Fatty aldehyde dehydrogenase had high activity towards saturated and unsaturated aliphatic aldehydes ranging from 6 to 24 carbons in length, as well as dihydrophytal, a 20-carbon branched chain aldehyde. In contrast, acetaldehyde, propionaldehyde, crotonaldehyde, glutaraldehyde, benzaldehyde, and retinaldehyde were poor substrates. The enzyme was inhibited by disulfiram, iodoacetamide, alpha,p-dibromoacetophenone, and p-chloromercuribenzoate. These results indicate that microsomal fatty aldehyde dehydrogenase is a distinct human aldehyde dehydrogenase isozyme that acts on a variety of medium- and long-chain aliphatic substrates. << Less

  Biochim. Biophys. Acta 1335:99-110(1997) [PubMed] [EuropePMC]

• A gatekeeper helix determines the substrate specificity of Sjogren-Larsson Syndrome enzyme fatty aldehyde dehydrogenase.

  Keller M.A., Zander U., Fuchs J.E., Kreutz C., Watschinger K., Mueller T., Golderer G., Liedl K.R., Ralser M., Krautler B., Werner E.R., Marquez J.A.

  Mutations in the gene coding for membrane-bound fatty aldehyde dehydrogenase (FALDH) lead to toxic accumulation of lipid species and development of the Sjögren-Larsson Syndrome (SLS), a rare disorder characterized by skin defects and mental retardation. Here, we present the crystallographic struct ... >> More

  Mutations in the gene coding for membrane-bound fatty aldehyde dehydrogenase (FALDH) lead to toxic accumulation of lipid species and development of the Sjögren-Larsson Syndrome (SLS), a rare disorder characterized by skin defects and mental retardation. Here, we present the crystallographic structure of human FALDH, the first model of a membrane-associated aldehyde dehydrogenase. The dimeric FALDH displays a previously unrecognized element in its C-terminal region, a 'gatekeeper' helix, which extends over the adjacent subunit, controlling the access to the substrate cavity and helping orientate both substrate cavities towards the membrane surface for efficient substrate transit between membranes and catalytic site. Activity assays demonstrate that the gatekeeper helix is important for directing the substrate specificity of FALDH towards long-chain fatty aldehydes. The gatekeeper feature is conserved across membrane-associated aldehyde dehydrogenases. Finally, we provide insight into the previously elusive molecular basis of SLS-causing mutations. << Less

  Nat. Commun. 5:4439-4439(2014) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification.

  Kitamura T., Takagi S., Naganuma T., Kihara A.

  Aldehyde dehydrogenases (ALDHs) catalyse the conversion of toxic aldehydes into non-toxic carboxylic acids. Of the 21 ALDHs in mice, it is the ALDH3 family members (ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2 and ALDH3B3) that are responsible for the removal of lipid-derived aldehydes. However, ALDH3B2 and ... >> More

  Aldehyde dehydrogenases (ALDHs) catalyse the conversion of toxic aldehydes into non-toxic carboxylic acids. Of the 21 ALDHs in mice, it is the ALDH3 family members (ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2 and ALDH3B3) that are responsible for the removal of lipid-derived aldehydes. However, ALDH3B2 and ALDH3B3 have yet to be characterized. In the present study, we examined the enzyme activity, tissue distribution and subcellular localization of ALDH3B2 and ALDH3B3. Both were found to exhibit broad substrate preferences from medium-to long-chain aldehydes, resembling ALDH3A2 and ALDH3B1. Although ALDH3B2 and ALDH3B3 share extremely high sequence similarity, their localizations differ, with ALDH3B2 found in lipid droplets and ALDH3B3 localized to the plasma membrane. Both were modified by prenylation at their C-termini; this modification greatly influenced their membrane localization and enzymatic activity towards hexadecanal. We found that their C-terminal regions, particularly the two tryptophan residues (Trp462 and Trp469) of ALDH3B2 and the two arginine residues (Arg462 and Arg463) of ALDH3B3, were important for the determination of their specific localization. Abnormal quantity and perhaps quality of lipid droplets are implicated in several metabolic diseases. We speculate that ALDH3B2 acts to remove lipid-derived aldehydes in lipid droplets generated via oxidative stress as a quality control mechanism. << Less

  Biochem. J. 465:79-87(2015) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.