Human liver fatty aldehyde dehydrogenase: Microsomal localization, purification, and biochemical characterization

Todd L. Kelson, Julie R. Secor McVoy, William B. Rizzo

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

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 54,000, required NAD+ as cofactor, had optimal activity at pH 9.8, and was thermolabile at 47°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, α,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.

Original languageEnglish (US)
Pages (from-to)99-110
Number of pages12
JournalBiochimica et Biophysica Acta - General Subjects
Volume1335
Issue number1-2
DOIs
Publication statusPublished - Apr 17 1997

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Keywords

  • Aldehyde dehydrogenase
  • Fatty alcohol
  • Fatty aldehyde
  • Human liver
  • Microsomal
  • Sjogren-Larsson syndrome

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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