Molecular cloning, expression and functional characterization of the cytochrome P450 2A6 gene in pig liver

被引:29
作者
Lin, Z [1 ]
Lou, Y [1 ]
Squires, EJ [1 ]
机构
[1] Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada
关键词
cytochrome P4502A6; gene expression; genetic polymorphism; skatole;
D O I
10.1111/j.1365-2052.2004.01140.x
中图分类号
S8 [畜牧、 动物医学、狩猎、蚕、蜂];
学科分类号
0905 ;
摘要
Raising intact male pigs would have a significant economic impact on the pork industry because intact males have improved feed efficiency and a greater lean yield of the carcass compared with barrows. However, the presence of skatole, a major cause of boar taint, in meat from intact male pigs could be highly objectionable to consumers. It has been shown that CYP2A6 is a key enzyme in the hepatic metabolism of skatole and that the activity of CYP2A6 is negatively correlated with skatole accumulation in fat. The aim of this study was to isolate and characterize CYP2A6 from pig liver, as well as identify genetic polymorphisms in the CYP2A6 gene, and examine the association between these polymorphisms and skatole level. We identified a single base deletion in CYP2A6, resulting in a frame shift in the coding region that produces a non-functional enzyme, which was associated with high levels of skatole in fat tissue.
引用
收藏
页码:314 / 316
页数:3
相关论文
共 9 条
[1]  
Ausubel FA, 1998, CURRENT PROTOCOLS MO
[2]  
Babol J, 1998, J ANIM SCI, V76, P829
[3]   Metabolism of 3-methylindole by porcine liver microsomes: Responsible cytochrome P450 enzymes [J].
Diaz, GJ ;
Squires, EJ .
TOXICOLOGICAL SCIENCES, 2000, 55 (02) :284-292
[4]   CYP2A6*6, a novel polymorphism in cytochrome P450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity [J].
Kitagawa, K ;
Kunugita, N ;
Kitagawa, M ;
Kawamoto, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (21) :17830-17835
[5]   Expression of CYP2A genes in human liver and extrahepatic tissues [J].
Koskela, S ;
Hakkola, J ;
Hukkanen, J ;
Pelkonen, O ;
Sorri, M ;
Saranen, A ;
Anttila, S ;
Fernandez-Salguero, P ;
Gonzalez, F ;
Raunio, H .
BIOCHEMICAL PHARMACOLOGY, 1999, 57 (12) :1407-1413
[6]   Molecular modelling of the human cytochrome P450 isoform CYP2A6 and investigations of CYP2A substrate selectivity [J].
Lewis, DFV ;
Dickens, M ;
Lake, BG ;
Eddershaw, PJ ;
Tarbit, MH ;
Goldfarb, PS .
TOXICOLOGY, 1999, 133 (01) :1-33
[7]   Molecular cloning and functional analysis of porcine SULT1A1 gene and its variant: a single mutation SULT1A1 causes a significant decrease in sulfation activity [J].
Lin, ZH ;
Lou, YP ;
Squires, EJ .
MAMMALIAN GENOME, 2004, 15 (03) :218-226
[8]  
SQUIRES EJ, 1988, J BIOL CHEM, V263, P4166
[9]   THE CYP2A3-GENE PRODUCT CATALYZES COUMARIN 7-HYDROXYLATION IN HUMAN LIVER-MICROSOMES [J].
YAMANO, S ;
TATSUNO, J ;
GONZALEZ, FJ .
BIOCHEMISTRY, 1990, 29 (05) :1322-1329