Human aldehyde dehydrogenases: Potential pathological, pharmacological, and toxicological impact

Abstract

Aldehyde dehydrogenases catalyze the pyridine nucleotide-dependent oxidation of aldehydes to acids. Seventeen enzymes are currently viewed as belonging to the human aldehyde dehydrogenase superfamily. Summarized herein, insofar as the information is available, are the structural composition, physical properties, tissue distribution, subcellular location, substrate specificity, and cofactor preference of each member of this superfamily. Also summarized are the chromosomal locations and organization of the genes that encode these enzymes and the biological consequences when enzyme activity is lost or substantially diminished. Broadly, aldehyde dehydrogenases can be categorized as critical for normal development and/or physiological homeostasis (1). even when the organism is in a friendly environment or (2). only when the organism finds itself in a hostile environment. The primary, if not sole, evolved raison d'être of first category aldehyde dehydrogenases appears to be to catalyze the biotransformation of a single endobiotic for which they are relatively specific and of which the resultant metabolite is essential to the organism. Most of the human aldehyde dehydrogenases for which the relevant information is available fall into this category. Second category aldehyde dehydrogenases are relatively substrate nonspecific and their evolved raison d'être seems to be to protect the organism from potentially harmful xenobiotics, specifically aldehydes or xenobiotics that give rise to aldehydes, by catalyzing their detoxification. Thus, the lack of a fully functional first category aldehyde dehydrogenase results in a gross pathological phenotype in the absence of any insult, whereas the lack of a functional second category aldehyde dehydrogenase is ordinarily of no consequence with respect to gross phenotype, but is of consequence in that regard when the organism is subjected to a relevant insult.

Flow cytometry in cancer stem cell analysis and separation

“…Nineteen isoforms of ALDH exist in humans and most of them are able to catalyze the oxidation of different aldehydes (129). The ALDH1 isoform catalyzes the conversion of retinol to retinoic acid in normal and malignant stem cells.…”

Identification of Human Aldehyde Dehydrogenase 1 Family Member A1 as a Novel CD8+ T-Cell–Defined Tumor Antigen in Squamous Cell Carcinoma of the Head and Neck

“…Known risks for development of SCCHN as well as its progression and recurrence include excessive alcohol and tobacco use and decreased retinoic acid synthesis (2)(3)(4). These two factors link the human aldehyde dehydrogenases (ALDH) to development as well as chemoprevention of SCCHN.…”

Oxidative Stress and Mitochondrial Aldehyde Dehydrogenase Activity: A Comparison of Pentaerythritol Tetranitrate with Other Organic Nitrates

“…However, the ALDH-2 concept was criticized in a recent study (DiFabio et al, 2003), because an appreciable number of Asiatic people possess a mutation of ALDH-2, which causes a loss of function, but yet show no signs of inherited tolerance to GTN. This apparent discrepancy may be explained if one recalls that this mutation affects the cofactor binding (Sladek, 2003), thereby probably leaving the ALDH-2 esterase and GTN reductase activity intact.…”