Phospholipase D activity of cytochrome P450 in human liver endoplasmic reticulum.
Phospholipase D (PLD) activity in mammalian liver endoplasmic reticulum (ER) has not been characterized. Purified human liver microsomal cytochromes P450 (P450)-P450 1A2 and P450 2E1-were shown to have appreciable PLD activity, hydrolyzing phosphatidylcholine but not other phospholipids, generating PA and choline. The activity was confirmed using recombinant and mutated human P450s expressed in bacteria. In human liver microsomes, immunoinhibition of PLD activity was observed with anti-P450 1A2 > anti-P450 2C > anti-P450 2E1. Thus, P450 may act as a significant PLD in human liver ER and exert its biological effects by several mechanisms, including signaling functions and change of membrane properties.
Yun
C H
CH
Department of Biochemistry, Pai-Chai University, Taejon, 302-735, Korea. chyun@woonam.paichai.ac.kr
Ahn
T
T
Guengerich
F P
FP
Yamazaki
H
H
Shimada
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D013379:Substrate Specificity
D000906:Antibodies; D065607:Cytochrome P-450 Enzyme Inhibitors; D003902:Detergents; D005227:Fatty Acids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D010739:Phospholipase D; D002794:Choline; D002118:Calcium