TY - JOUR
T1 - Effects of a choline-deficient diet on the induction of drug- and ethanol-metabolizing enzymes and on the alteration of rates of ethanol degradation by ethanol and phenobarbital
AU - Mezey, Esteban
AU - Potter, James J.
AU - Brandes, David
N1 - Funding Information:
Acknowledgements -. This work was supported by Grant 5 R01 MH 14251 from the National Institutes of Mental Health, United States Public Health Service.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1975/11/1
Y1 - 1975/11/1
N2 - Phosphatidylcholine has been shown to be an essential component for electron transport to cytochrome P-450 and for hydroxylation of a number of substrates by microsomes in vitro. A choline-deficient diet was fed to rats for 3 weeks in order to study the effect in vivo of alterations of liver phospholipids on the activity of microsomal enzymes, on parameters of ethanol metabolism, and on the adaptive responses of both to ethanol and phenobarbital administration. Choline deficiency resulted in an increase in total liver lipids and triglycerides, but in a decrease in total phospholipids, due mostly to a decrease in phosphatidylcholine. Choline deficiency did not result in changes in microsomal enzymes or parameters of ethanol metabolism. However, it did prevent optimal induction of aniline hydroxylase activity and cytochrome P-450, by both ethanol and phenobarbital, and of microsomal protein concentration and cytochrome b5 by phenobarbital; it also prevented ethanol-induced increases both in the activity of the microsomal ethanol-oxidizing system and in the rates of ethanol disappearance from the blood. Alcohol dehydrogenase activity remained unchanged. This study demonstrates that dietary choline is required for optimal induction of microsomal enzymes by both ethanol and phenobarbital, and for increases in ethanol metabolism induced by ethanol administration. It is suggested that a decrease in available hepatic phosphatidylcholine, due to choline deficiency, is a cause of inhibition of the optimal induction of microsomal enzymes.
AB - Phosphatidylcholine has been shown to be an essential component for electron transport to cytochrome P-450 and for hydroxylation of a number of substrates by microsomes in vitro. A choline-deficient diet was fed to rats for 3 weeks in order to study the effect in vivo of alterations of liver phospholipids on the activity of microsomal enzymes, on parameters of ethanol metabolism, and on the adaptive responses of both to ethanol and phenobarbital administration. Choline deficiency resulted in an increase in total liver lipids and triglycerides, but in a decrease in total phospholipids, due mostly to a decrease in phosphatidylcholine. Choline deficiency did not result in changes in microsomal enzymes or parameters of ethanol metabolism. However, it did prevent optimal induction of aniline hydroxylase activity and cytochrome P-450, by both ethanol and phenobarbital, and of microsomal protein concentration and cytochrome b5 by phenobarbital; it also prevented ethanol-induced increases both in the activity of the microsomal ethanol-oxidizing system and in the rates of ethanol disappearance from the blood. Alcohol dehydrogenase activity remained unchanged. This study demonstrates that dietary choline is required for optimal induction of microsomal enzymes by both ethanol and phenobarbital, and for increases in ethanol metabolism induced by ethanol administration. It is suggested that a decrease in available hepatic phosphatidylcholine, due to choline deficiency, is a cause of inhibition of the optimal induction of microsomal enzymes.
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U2 - 10.1016/0006-2952(75)90385-8
DO - 10.1016/0006-2952(75)90385-8
M3 - Article
C2 - 1212248
AN - SCOPUS:0016747393
SN - 0006-2952
VL - 24
SP - 1975
EP - 1981
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 21
ER -