Cytochrome P450 4A, peroxisomal enzymes and nicotinamide cofactors in koala liver.
We have examined hepatic levels of microsomal lauric acid hydroxylase activity and cyanide-insensitive palmitoyl coenzyme A oxidative activity in koala (Phascolarctos cinereus) and tammar wallaby (Macropus eugenii) and compared our results to those determined in rat. Microsomal lauric acid hydroxylation was significantly higher in koala than in tammar wallaby or rat. However, cyanide-insensitive palmitoyl-CoA oxidation was absent in the koala. We have also determined the hepatic nicotinamide cofactors in these species. Hepatic nicotinamide-adenine dinucleotide (NAD) and the ratio of NAD/nicotinamide-adenine dinucleotide phosphate (NADP) were higher in koala than in tammar wallaby and rat liver. Reverse transcription of koala liver mRNA, followed by polymerase chain reaction using primers based on highly conserved areas in the CYP4A family led to the cloning of a partial, near full length, cDNA clone with approximately 70% nucleotide and deduced amino acid sequence identity to human CYP4A11. The CYP has been named CYP4A15.
Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
S
S
Ngo
S
S
Kong
A
A
Kirlich
R A
RA
McKinnon
I
I
Stupans
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008394:Marsupialia / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism*; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D020675:Peroxisomes / Q000201:enzymology*; D051381:Rats; D013045:Species Specificity
D018076:DNA, Complementary; D009243:NAD; D010171:Palmitoyl Coenzyme A; D009536:Niacinamide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A