Developmental Changes of Aldehyde Oxidase Activity and Protein Expression in Human Liver Cytosol

Aldehyde oxidase (AO) plays a role in metabolizing many drugs, such as methotrexate and 6-mercaptopurine. We previously showed that AO activity in rat liver rapidly increases from birth, reaching a plateau within 4 weeks, and is regulated at the protein expression level. However, developmental chang...

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Bibliographic Details
Published in:Drug metabolism and pharmacokinetics 2012, Vol.27 (5), p.543-547
Main Authors: Tayama, Yoshitaka, Sugihara, Kazumi, Sanoh, Seigo, Miyake, Katsushi, Kitamura, Shigeyuki, Ohta, Shigeru
Format: Article
Language:English
Subjects:
Adolescent
Adult
aldehyde oxidase
Aldehyde Oxidase - metabolism
Child
Child, Preschool
children
Cytosol - enzymology
Cytosol - metabolism
developmental change
Female
human
Humans
Infant
Infant, Newborn
liver
Liver - enzymology
Liver - metabolism
Male
Middle Aged
Niacinamide - analogs & derivatives
Niacinamide - metabolism
Oxidation-Reduction
Pyridones - metabolism
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Summary:Aldehyde oxidase (AO) plays a role in metabolizing many drugs, such as methotrexate and 6-mercaptopurine. We previously showed that AO activity in rat liver rapidly increases from birth, reaching a plateau within 4 weeks, and is regulated at the protein expression level. However, developmental changes of AO activity and protein expression in human liver have not been reported. Here, we investigated the developmental changes and variability of AO in 16 human livers (13 children ranging from 13 days to 12 years old and 3 adults, 17, 34 and 45 years old). Young children (13 days to 4 months after birth) showed little liver AO activity, evaluated in terms of the activities for oxidation of N-1-methylnicotinamide to N-1-methyl-2-pyridone-5-carboxamide and N-1-methyl-4-pyridone-3-carboxamide in liver cytosol. However, these oxidase activities were markedly increased after 4 months, reaching the adult level by about 2 years of age. The AO band density in immunoblotting analysis was well correlated with the AO activity among all subjects (p < 0.01, r2 = 0.771). Therefore, AO activity in the liver of young children is regulated at the AO protein expression level. Thus, as in rats, the AO activity in humans rapidly increases soon after birth, and is regulated at the protein expression level.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.DMPK-11-NT-124