Satori A Marchitti1, Chad Brocker, Dimitrios Stagos, Vasilis Vasiliou. 1. University of Colorado Health Sciences Center, Molecular Toxicology & Environmental Health Sciences Program, Department of Pharmaceutical Sciences, 4200 East Ninth Avenue, C238, Denver, Colorado 80262, USA.
Abstract
BACKGROUND: Aldehydes are highly reactive molecules. While several non-P450 enzyme systems participate in their metabolism, one of the most important is the aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation. OBJECTIVE: This article presents a review of what is currently known about each member of the human ALDH superfamily including the pathophysiological significance of these enzymes. METHODS: Relevant literature involving all members of the human ALDH family was extensively reviewed, with the primary focus on recent and novel findings. CONCLUSION: To date, 19 ALDH genes have been identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, gamma-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. Finally, ALDH enzymes display multiple catalytic and non-catalytic functions including ester hydrolysis, antioxidant properties, xenobiotic bioactivation and UV light absorption.
BACKGROUND:Aldehydes are highly reactive molecules. While several non-P450 enzyme systems participate in their metabolism, one of the most important is the aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation. OBJECTIVE: This article presents a review of what is currently known about each member of the human ALDH superfamily including the pathophysiological significance of these enzymes. METHODS: Relevant literature involving all members of the human ALDH family was extensively reviewed, with the primary focus on recent and novel findings. CONCLUSION: To date, 19 ALDH genes have been identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, gamma-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. Finally, ALDH enzymes display multiple catalytic and non-catalytic functions including ester hydrolysis, antioxidant properties, xenobiotic bioactivation and UV light absorption.
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