Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.2.1.3

Official Name

aldehyde dehydrogenase (NAD+)

Name from literature

aldehyde dehydrogenase

Pathway from literature

acetaldehyde metabolism

Pathway from KEGG

Xenobiotics Biodegradation and Metabolism; 1,2-Dichloroethane degradation; map00631

Xenobiotics Biodegradation and Metabolism; 3-Chloroacrylic acid degradation; map00641

Amino Acid Metabolism; Tryptophan metabolism; map00380

Biosynthesis of Secondary Metabolites; Limonene and pinene degradation; map00903

Lipid Metabolism; Bile acid biosynthesis; map00120

Carbohydrate Metabolism; Butanoate metabolism; map00650

Amino Acid Metabolism; Urea cycle and metabolism of amino groups; map00220

Lipid Metabolism; Fatty acid metabolism; map00071

Carbohydrate Metabolism; Propanoate metabolism; map00640

Carbohydrate Metabolism; Pyruvate metabolism; map00620

Carbohydrate Metabolism; Glycolysis / Gluconeogenesis; map00010

Carbohydrate Metabolism; Ascorbate and aldarate metabolism; map00053

Lipid Metabolism; Glycerolipid metabolism; map00561

Amino Acid Metabolism; Valine, leucine and isoleucine degradation; map00280

Amino Acid Metabolism; Histidine metabolism; map00340

Amino Acid Metabolism; Lysine degradation; map00310

Metabolism of Other Amino Acids; beta-Alanine metabolism; map00410

Organisms

Human (9606)

Genome localization

15q26.3[220 ], 1q23.1[223 ], 17p11.2[218 ], 9p11.1[219 ], 12q24.2[217 ], 5q31[501 ], 17p11.2[224 ],

Comments

Wide specificity, including oxidation of D-glucuronolactone to D-glucarate.

Rate-limiting Description

"Both the rat native enzyme and the E487K mutant oxidized chloroacetaldehyde twice as fast as acetaldehyde, indicating that the rate-limiting step was not hydride transfer or coenzyme dissociation but depended upon nucleophilic attack." (7910607)

"The basis for the change in the rate-limiting step appears to be related to NAD(+) binding." (16878979)

"The rate-limiting step remained deacylation for the E399H/D mutants when either aliphatic or aromatic aldehydes were used as substrates." (9228057)

Regulatory Information

Upstream transcription factor

6256

Regulatory type

Detail

transcriptional level;

"Using a reporter gene assay, we have identified tissue-specific regulatory elements that govern ALDH1 expression in primary retina and liver cultures. " (11438538)

key enzyme;

"Acetaldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism." (17984618#16499490)

inhibitor;

"In vitro contraction experiments were performed in the presence or absence of the ALDH inhibitors chloral hydrate, cyanamide, and ethoxycyclopropanol. Concentration response curves were determined for the alpha-agonist phenylephrine, nitroglycerin, and the direct NO donor diethylamine NONOate (DEA-NONOate)." (18272654)

transcriptional level;

"The human aldehyde dehydrogenase-2 promoter contains a retinoid response element which may contribute to regulation of the retinoic acid receptor." (14691372)

phosphorylation;

P05091

phosphorylation;

P30837

phosphorylation;

P49189

transcriptional level;Smad/Foxh1

"The Aldh1a family is required for retinoic acid (RA) synthesis, and, in Foxh1 mutants, expression of Aldh1a1, -2, and -3 and activation of a RA-responsive transgenic reporter is abolished in anterior structures. Integrated mapping of a developmental transcription factor network thus reveals a key role for Foxh1 in patterning and initiating RA signaling in the forebrain." (18331719)

transcriptional factor;RXRalpha(6256)

"Heterodimers of retinoic acid receptor (RAR)alpha, beta, and gamma with retinoid X receptor (RXR)alpha bound the FP330-3' site. Mutagenesis of the FP330-3' site suggested that either the upstream DR-5 or downstream DR-1 could mediate binding of RAR/RXR." (14691372)

Gene ontology

Gene ontology

GO:0007422 (P) peripheral nervous system development [P51648 ];
GO:0047105 (F) 4-trimethylammoniobutyraldehyde dehydrogena... [P49189 ];
GO:0019145 (F) aminobutyraldehyde dehydrogenase activity [P49189 ];
GO:0006629 (P) lipid metabolic process [P51648 ];
GO:0006066 (P) cellular alcohol metabolic process [P05091 ];
GO:0042136 (P) neurotransmitter biosynthetic process [P49189 ];
GO:0006081 (P) cellular aldehyde metabolic process [P51648, P49189 ];
GO:0004030 (F) aldehyde dehydrogenase [NAD(P)+] activity [P51648, P05091 ];
GO:0005975 (P) carbohydrate metabolic process [P30837, P05091 ];
GO:0016021 (C) integral to membrane [P51648 ];
GO:0009055 (F) electron carrier activity [P05091 ];
GO:0008544 (P) epidermis development [P51648 ];
GO:0042445 (P) hormone metabolic process [P49189 ];
GO:0005789 (C) endoplasmic reticulum membrane [P51648 ];
GO:0005759 (C) mitochondrial matrix [P30837, P05091 ];
GO:0007417 (P) central nervous system development [P51648 ];
GO:0005634 (C) nucleus [P49189 ];
GO:0004029 (F) aldehyde dehydrogenase (NAD) activity [P30837, P51648, P49189, P05091 ];
GO:0005856 (C) cytoskeleton [P49189 ];
GO:0055114 (P) oxidation reduction [P30837, P51648, P49189, P05091 ];
GO:0004028 (F) 3-chloroallyl aldehyde dehydrogenase activity [P51648 ];

Tissue expression

Tissue From HPRD

Saliva [00004 ];
Salivary gland [02713 ];
Fetus [00005, 00124 ];
Oesophagus [00004 ];
Hepatocyte [02713 ];
Testis [02713, 00005 ];
Skeletal muscle [02713, 07188 ];
Liver [02713, 00005, 00003, 07188, 00004, 04109 ];
Keratinocyte [07188 ];
Brain [02713, 00005, 00003, 07188, 04109 ];
Muscle [00005, 00003, 04109 ];
Spleen [00003 ];
Kidney [02713, 00005, 00003, 07188, 00004, 04109 ];
Parotid gland [02713 ];
Mammary gland [02713 ];
Adrenal gland [02713, 04109 ];
Lung [02713, 00003, 07188, 00004 ];
Heart [00005, 00003, 07188, 04109 ];
Epidermis [07188 ];
Pancreas [02713, 07188, 04109 ];
Ovary [00003 ];
Hair [00004 ];
Placenta [02713, 00005 ];
Stomach [02713, 00003, 00004 ];

Tissue specificity

High expression in adult liver, skeletal muscle, and kidney. Low levels in heart, pancreas, lung and brain. Expressed in all regions of the brain. Expression levels are variable in the different brain areas, with the highest levels in the spinal cord and the lowest in the occipital pole [P49189 ];

Liver, testis and to a lesser extent in brain [P30837 ];

Subcellular localization

Localization

mitochondrion [P30837, P05091 ];

endoplasmic reticulum [P51648 ];

cytoplasm [P51648, P49189 ];

Disease relevance

Disease

Defects in ALDH3A2 are the cause of Sjoegren-Larsson syndrome (SLS) [MIM:270200]. SLS is an autosomal recessive neurocutaneous disorder characterized by a combination of severe mental retardation, spastic di- or tetraplegia and congenital ichthyosis (increased keratinization). Ichthyosis is usually evident at birth, neurologic symptoms appear in the first or second year of life. Most patients have an IQ of less than 60. Additional clinical features include glistening white spots on the retina, seizures, short stature and speech defects [P51648 ];

Links

SwissProt

P05091; P30837; P49189; P51648

Entrez Gene

217; 218; 219; 220; 223; 224; 501

HPRD

00003; 07188; 00004; 00005; 04109; 02713; 00124



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min