TY - JOUR
T1 - Structure and function of mammalian aldehyde oxidases
AU - Terao, Mineko
AU - Romão, Maria João
AU - Leimkuehler, Silke
AU - Bolis, Marco
AU - Fratelli, Maddalena
AU - Coelho, Catarina Maria Campos
AU - Santos-Silva, Teresa Sacadura
AU - Garattini, Enrico
N1 - Sem PDF.
Fondazione Italo Monzino
Associazione Italiana per la Ricerca contro il Cancro (AIRC)
Deutsche Forschungsgemeinschaft (DFG)
LE1171/8-1
Fundacao para a Ciencia e Tecnologia (UID/Multi/04378/2013; PTDC/BBB-BEP/1185/2014; EXCL/QEQ-COM/0394/2012; PTDC/BIA-PRO/118377/2010;
SFRH/BPD/84581/2012; DAAD-441.00)
PY - 2016/4
Y1 - 2016/4
N2 - Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX.
AB - Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX.
KW - Aldehyde oxidase
KW - Molybdo-flavoenzymes
KW - Xanthine oxidoreductase
KW - Drug metabolism
U2 - 10.1007/s00204-016-1683-1
DO - 10.1007/s00204-016-1683-1
M3 - Literature review
C2 - 26920149
SN - 0340-5761
VL - 90
SP - 753
EP - 780
JO - Archives Of Toxicology
JF - Archives Of Toxicology
IS - 4
ER -