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Official Full Name
Aldehyde dehydrogenase from yeast catalyzes the following reaction: RCHO + NAD/NADP+ + H2O → RCOOH + NADH/NADPH+ + H+. The yeast enzyme requires potassium ions and thiols (glutathione, 2-mercaptoethanol, cysteine) for its activity. It is inhibited by traces of heavy metals, particularly copper. Similar enzymes, but with different requirements for their catalytic activities, have been purified from equine liver and from human erythrocytes. The enzyme from yeast has a molecular weight of 200,000.
aldehyde dehydrogenase [NAD(P)+]; Aldehyde: NAD+ (P+) oxi1doreductase; EC; Aldehyde Dehydrogenase; ALDH

EC No.
CAS No.9028-88-0
CAS No.9028-88-0
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Related Protocols
aldehyde_dehydrogenase -Enzymatic Assay Protocol
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Aldehyde dehydrogenase (EC catalyzes dehydrogenation of a large variety of aldehydes in the presence of nicotinamide adenine dinucleotide (NAD+) as the coenzyme. They convert aldehydes (R–C(=O)–H) to carboxylic acids (R–C(=O)–O–H). The oxygen comes from a water molecule. Aldehyde dehydrogenases (ALDHs) belong to a superfamily of enzymes that play a key role in the metabolism of aldehydes of both endogenous and exogenous derivation. The human ALDH superfamily comprises 19 isozymes that possess important physiological and toxicological functions.


Aldehyde dehydrogenases (ALDH) belong to the oxidoreductase family. The human ALDH superfamily comprises 19 isozymes. The genes coding for human aldehyde dehydrogenases of broad substrate specificity are: aldh1, aldh2, aldh3, aldh9 and aldh10. The ALDH1A subfamily plays a pivotal role in embryogenesis and development by mediating retinoic acid signaling. ALDH2, as a key enzyme that oxidizes acetaldehyde, is crucial for alcohol metabolism. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissues. Many ALDH isozymes are important in oxidizing reactive aldehydes derived from lipid peroxidation and thereby help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes have been reported in various human cancers and are associated with cancer relapse.


ALDH Figure 1. A ribbon drawing of the ALDH3 dimer and monomer. (Liu Z J, et al. 1997)

Here we discuss the three dimensional structure of ALDH3. The active form of the enzyme is a dimer, consisting of the two identical 452 residue subunits. Each subunit contains an NAD(P)-binding, a catalytic and an “arm-like” bridging domain. The subunits in the dimer are related by a pseudo two-fold symmetry. The dimer is stabilized by a total of 62 intra-molecular hydrogen bonds. N-terminal residues form a cluster of four helices, α1-α4. The polypeptide chain then loops away to begin the “arm-like” bridging domain, forming strand β0, and returns to form the characteristic open α/β structure of a dinucleotide-binding Rossmann fold. The polypeptide chain continues into the catalytic domain, which also exhibits an α/β motif consisting of six parallel strands, β6-β7-β9-β10-β11-β12, one antiparallel strand, β8, and five helices, α9-α13. The chain then extends back over the NAD-binding domain forming α14 and then β13. This strand completes a two-stranded antiparallel β-ribbon with β0, which becomes part of the catalytic pocket of the other subunit. The C-terminal residues form a loop over the catalytic domain of the other subunit completing the bridging domain. The bridging domain, which forms 29 hydrogen bonds with the catalytic domain of the other subunit, plays an important role in the formation and stabilization of the dimer.


The NAD(P)+-dependent reaction catalyzed by ALDH is: RCHO + NAD+ + H2O → RCOOH + NADH + H+. In this reaction, the aldehyde enters the active site through a channel extending from the surface of the enzyme. The active site contains a Rossman fold, and interactions between the cofactor and the fold allow for the action of the active site.

ALDHFigure 2. Mechanism of Aldehyde Dehydrogenase.

A sulfur from a cysteine in the active site makes a nucleophilic attack on the carbonyl carbon of the aldehyde. The hydrogen is kicked off as a hydride and attacks NAD(P)+ to make NAD(P)H. The enzyme's active site then goes through an isomorphic change whereby the NAD(P)H is moved, creating room for a water molecule to access the substrate. The water is primed by a glutamate in the active site, and the water makes a nucleophilic attack on the carbonyl carbon, kicking off the sulfur as a leaving group.


ALDH is an NAD(P)-dependent enzyme and is widely distributed in virtually all tissues in plants and animals. In mammals, ALDH exist as distinct enzymes with different tissue specificities, found in a number of different locations within the body, including liver, stomach, kidney, eye and brain. Although these enzymes have a similar general function—the detoxification of aldehydes—the individual enzymes have different specificities, reflecting their specific biological roles. Human liver ALDH, for example, is one of the two key enzymes that are responsible for alcohol metabolism: alcohol dehydrogenase (ADH) converts alcohol to aldehyde and ALDH converts aldehyde to carboxylic acid, which can then be eliminated or used in other metabolic pathways. A mutation in the human fatty aldehyde dehydrogenase has been linked to the Sjögren–Larsson syndrome, an inborn neurologic impairment. In plants, the nuclear restorer protein of male-sterile T-cytoplasm maize, RF2, is a putative ALDH with ~60% identity and 75% similarity to mammalian ALDH. ALDH has also been found to play an important role in pheromone metabolism and developmental processes. A change in ALDH activity has also been observed in a number of tumors, including liver, colon and mammary cancers and a model of inducible ALDH gene regulation has been proposed.


  1. Liu Z J, et al. The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold. Nat Struct Biol, 1997, 4(4):317-326.
  2. Nicolaou C, et al. Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacological Reviews, 2012, 64(3):520-39.

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