title: Dead enzymes in the aldehyde dehydrogenase gene family: role in drug metabolism and toxicology.
abstract: BACKGROUND
  Dead enzymes are gene products (proteins) that lack key residues required for catalytic activity. In the pre-genome era, dead enzymes were thought to occur only rarely. However, they now have been shown to represent upwards of 10% of the total enzyme population in many families. The aldehyde dehydrogenase (ALDH) gene family encodes proteins that, depending on the isozyme, may be either catalytically-active or -inactive. Importantly, several ALDHs exhibit biological activities independent of their catalytic activity. For many of these, the physiological and pathophysiological functions remain to be established.
  
  
  METHODS
  This article reviews the non-enzymatic functions of the ALDH superfamily. In addition, a search for additional non-catalytic ALDH records is undertaken. Our computational analyses reveal that there are currently 182 protein records (divided into 19 groups) that meet the criteria for dead enzymes.
  
  
  CONCLUSIONS
  Dead enzymes have the potential to exert biological actions through protein-protein interaction and allosteric modulation of the activity of an active enzyme. In addition, a dead enzyme may also influence availability of substrate for other active enzymes by sequestering substrate, and/or anchoring the substrate to a particular subcellular space. A large number of putatively non-catalytic ALDH proteins exist that warrant further study.
authors.affiliation: a Department of Pharmaceutical Sciences , University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora , CO 80045 , USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jackson
authors.affiliation: b Department of Clinical Pharmacy , University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora , CO 80045 , USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Thompson
authors.affiliation: c Department of Environmental Health Sciences , Yale School of Public Health , 60 College St, New Haven , CT 06250 , USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Charkoftaki
authors.affiliation: c Department of Environmental Health Sciences , Yale School of Public Health , 60 College St, New Haven , CT 06250 , USA.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D002384:Catalysis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D000444:Aldehyde Dehydrogenase
keywords: aldehyde dehydrogenase; computational analysis; dead enzymes