Format

Send to

Choose Destination
Expert Opin Drug Metab Toxicol. 2015;11(12):1839-47. doi: 10.1517/17425255.2016.1108406. Epub 2015 Nov 11.

Dead enzymes in the aldehyde dehydrogenase gene family: role in drug metabolism and toxicology.

Author information

1
a Department of Pharmaceutical Sciences , University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora , CO 80045 , USA.
2
b Department of Clinical Pharmacy , University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora , CO 80045 , USA.
3
c Department of Environmental Health Sciences , Yale School of Public Health , 60 College St, New Haven , CT 06250 , USA.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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.

KEYWORDS:

aldehyde dehydrogenase; computational analysis; dead enzymes

PMID:
26558415
PMCID:
PMC4937717
DOI:
10.1517/17425255.2016.1108406
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center