Relationship between lipid composition and drug metabolizing capacity of human liver

Abstract

The relationship between hepatic glycerolipids and microsomal drug-metabolizing enzymes was studied in liver biopsies from 41 subjects. The series included obese, diabetic, epileptic and chronic alcoholic patients, all of whom were hospitalized for suspected hepatic ailments (fatty liver, hepatitis or cirrhosis). Therapy with enzyme-inducing anticonvulsants was associated with high phospholipid and cytochrome P-450 and low triacylglycerol concentration in the liver. In patients with fatty liver or cirrhosis low phospholipid and cytochrome P-450 and high triacylglycerol concentrations were observed. There was a significant correlation (r (Pearson's product moment correlation coefficient) = 0.91) between the hepatic phospholipid and cytochrome P-450 concentration. The cytochrome P-450 concentration was inversely related (r = -0.74) to the triacylglycerol concentration. The positive correlation between hepatic phospholipids and drug-metabolizing enzymes could be interpreted as indicating that in human liver phospholipid and cytochrome P-450 synthesis share common regulators, or that phospholipids are necessary for the maximum rate of cytochrome P-450 synthesis.

Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B1

“…When considering the structural changes of the microsomal membranal environment, one must recognize that the activities of other important enzymes are also likely to be altered. Changes in the Chol and phospholipid membrane constituents have been shown to alter the activities of drug-metabolizing enzymes, such as cytochrome P450 (33)(34)(35)(36)(37). In this regard, recent studies indicated that the activity of certain isozymes of the hepatic P450 enzyme system are selectively inhibited and/or stimulated by FB 1 (38,39).…”

Relevance of liver failure for anti-infective agents: from pharmacokinetic alterations to dosage adjustments

“…In alcoholic patients, anti-CYP2E1 and anti-CYP3A4 IgG antibodies have been detected [Lytton et al , 1999]. In addition, alterations in the lipid composition of hepatic glycerolipids have been correlated to decline in CYP450 concentrations [Savolainen et al , 1985]. In reality, a combination of several mechanisms are likely involved in the decreased metabolic ability of the liver during cirrhosis [Elbekai et al , 2004].…”

Mlicrosomal Enzyme Induction, Lipoproteins and Atherosclerosis

“…Estabrook & Lindenlaub 1979;Sotaniemi & Pelkonen 1987). The increase in liver protein and phospholipid concentrations in subjects treated with inducing drugs parallels the enhancement of microsomal enzyme activity as assessed by hepatic cytochrome P-450 or antipyrine kinetics (Luoma et al 1982b;Savolainen et al 1985). Microsomal inducers also influence triglyceride metabolism.…”

“…Microsomal inducers also influence triglyceride metabolism. They seem to promote triglyceride elimination and reduce triglyceride concentrations in human liver (Luoma et al 1983a;Savolainen et al 1985). Microsoma1 inducers also stimulate the rate-limiting enzyme of cholesterol synthesis, HMGCoA reductase, and 7a-hydroxylase, which is the rate-limiting, cytochrome P-450-linked enzyme in the synthesis of bile acids (Coyne et al 1976).…”

“…Relationships between serum and liver lipids, proteins and apopro teins. Subjects on inducing drugs have high phospholipid and protein and low triglyceride concentrations in the liver (Luoma et al 1983a;Savolainen et al 1985). Serum HDL-C and apo A-I levels and HDL-C/T-C ratios are directly proportional to liver phospholipid and protein concentrations ( fig.…”