Human aldehyde dehydrogenase gene family

Abstract

Twelve aldehyde dehydrogenase (ALDH) genes have been identified in humans. These genes, located on different chromosomes, encode a group of enzymes which oxidizes varieties of aliphatic and aromatic aldehydes. Metabolic disorders and clinical problems associated with mutations of ALDH1, ALDH2, ALDH4, ALDH10 and succinic semialdehyde (SSDH) genes have been emerged. Comparison of the human ALDHs indicates a wide range of divergency (Ͼ 80ϪϽ 15% identity at the protein sequence level) among them. However, several protein regions, some of which are implicated in functional activities, are conserved in the family members.The phylogenic tree constructed of 56 ALDH sequences of humans, animals, fungi, protozoa and eubacteria, suggests that the present-day human ALDH genes were derived from four ancestral genes that existed prior to the divergence of Eubacteria and Eukaryotes. The neighbor-joining tree derived from 12 human ALDHs and antiquitin indicates that diversification within the ALDH1/2/5/6 gene cluster occurred during the Neoproterozoic period (about 800 million years ago). Duplication in the ALDH 3/10/7/8 gene cluster occurred in Phanerozoic period (about 300 million years ago). Separations of ALDH3/ALDH10 and that of ALDH7/ALDH8 had occurred during the period of appearance and radiation of mammalian species.Keywords : gene family ; genomic organization; genetic disease; genetic variant; detoxification; evolution ; phylogenetic tree. This paper reviews the functional and structural diversity and Aldehyde dehydrogenases [aldehyde: NAD(P) ϩ oxidoreductase] are a group of enzymes catalyzing the conversion of alde-evolution of the human ALDH gene family.There is no uniform nomenclature system for human and hydes to the corresponding acids by means of an NAD(P) ϩ -dependent virtually irreversible reaction. ALDHs are widely dis-animal ALDH genes and enzymes. Therefore, commonly used abbreviated human gene symbols (GBD symbols) are used for tributed from bacteria to humans.Mammalian ALDH activity was first observed in ox liver genes (in italic) and enzymes (in non-italic) in the present review. GenBank identification numbers are also given. nearly 50 years ago [1] and thereafter several types of ALDH were distinguished based on their physico-chemical characteristics, enzymological properties, subcellular localization, and tissue distribution [2Ϫ4]. Two ALDH genes were cloned and char-Members of ALDH families acterized in 1985 [5]. At the present time, ten non-allelic genes Twelve known human ALDH genes and corresponding enhave been identified in the human ALDH family. In addition, zymes are listed in Proteins (enzyme subunits) encoded by these genes consist probably exist in other mammals. Protein sequences, genes and/ of about 500 amino acid residues. Catalytically active forms of or cDNAs for more than 50 animals, fungi, and bacterial ALDHs the enzymes are homodimers (ALDH3, ALDH4), homotetrahave been reported. mers (ALDH1, ALDH2, ALDH9, MMSDD) or unknown.

Significant improvement of stress tolerance in tobacco plants by overexpressing a stress-responsive aldehyde dehydrogenase gene from maize (Zea mays)

“…The aldehyde dehydrogenase (ALDH) superfamily comprises a group of divergently related enzymes that catalyze the irreversible NAD(P) + -dependent oxidation of a wide variety of aliphatic and aromatic aldehydes to their corresponding carboxylic acids and occur in most well-studied organisms (Yoshida et al 1998;Vasiliou et al 1999). To date, 22 ALDH families have been identified in eukaryotes, and 12 of them are present in plants (Sophos et al 2001;Kirch et al 2004).…”

“…To date, 22 ALDH families have been identified in eukaryotes, and 12 of them are present in plants (Sophos et al 2001;Kirch et al 2004). Many ALDHs are highly substratespecific, while others possess a broad range of substrates (Yoshida et al 1998;Perozich et al 1999). …”

The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) of Sulfolobus solfataricus: a key-enzyme of the semi-phosphorylative branch of the Entner–Doudoroff pathway

“…ALDHs catalyze the NAD(P) + -dependent oxidation of aldehydes to the corresponding carboxylic acids and play an important role in several cellular processes [e.g. glycolysis, detoxification, embryogenic development (Yoshida et al 1998)]. More recently, new archaeal members of the ALDH superfamily were characterized: (1) glyceraldehyde dehydrogenase [Picrophilus torridus , T. acidophilum (Jung and Lee 2006;, a constituent of the npED branch, and (2) 2,5-dioxopentanoate dehydrogenase involved in the catabolic D-arabinose pathway .…”

Kinetic modelling of the role of the aldehyde dehydrogenase enzyme and the breast cancer resistance protein in drug resistance and transport

“…Aldehyde dehydrogenases (ALDHs) [aldehyde: NAD(P) + oxidoreductase] are an enzyme group that catalyse the conversion of aldehydes to the corresponding acids irreversibly by means of an NAD(P) + -dependent reaction [22]. ALDHs are distinguished based on properties including physicochemical characteristics, enzymological, subcellular localisation and tissue distribution [23].…”