Increased oxidation and decreased conjugation of drugs in the liver caused by starvation. Altered metabolism of certain aromatic compounds and acetone.
Starvation causes several changes in the various processes of biotransformation. The focus of this review is on biotransformation of various aromatic and other compounds whose metabolism is catalyzed in phase I by isozymes belonging to the CYP2E1 gene subfamily, while in phase II phenol-UDPGT or conjugation with GSH play a dominant role. The other ways of conjugation are beyond the scope of this review. The reason why this aspect has been chosen is that the capacity of these reactions is profoundly altered by nutritional conditions. There is a balance between the two phases of biotransformation. Therefore, under standard circumstances in a well-fed state the intermediate formed in the course of phase I is converted to a conjugated compound rapidly, as a result of phase II. However, in starvation the pattern of drug metabolism is altered and the balance between the two phases is changed. This alteration of drug metabolism upon starvation is partly connected to the changes of cofactor supplies due to the metabolic state.
Mandl
J
J
1st Department of Biochemistry, Semmelweis University of Medicine, Budapest, Hungary.
Bánhegyi
G
G
Kalapos
M P
MP
Garzó
T
T
D000096:Acetone / Q000378:metabolism*; D001555:Benzene Derivatives / Q000378:metabolism*; D001711:Biotransformation; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics; D019800:Phenol; D010636:Phenols / Q000378:metabolism; D013217:Starvation / Q000378:metabolism*
D001555:Benzene Derivatives; D010636:Phenols; D000096:Acetone; D019800:Phenol; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D005978:Glutathione; D005947:Glucose