Fetal and adult human liver differ markedly in the fluidity and lipid composition of their microsomal membranes.

Abstract

The fluidity and lipid composition of the human hepatic microsomal membrane were studied in 11 livers from 16- to 21-week-old fetuses and in 5 adult livers, and compared with those of fetal and adult rat liver microsomes. Membrane fluidity was analyzed by measurement of fluorescence polarization using the fluorophore 1,6-diphenyl-1,3,5-hexatriene. The lipid apparent microviscosity (eta) of human fetal liver microsomes was 2.17 +/- 0.13 poise, as compared with 1.08 +/- 0.08 poise in adult liver (p less than 0.001). Similar differences in fluidity were found between fetal and adult rat liver microsomes. The more "fluid" adult microsomes had higher phospholipid/cholesterol and phosphatidylcholine/sphingomyelin molar ratios than those of the more "rigid" fetal microsomes. The degree of unsaturation of the adult microsomal lipids was much higher than that of the fetal lipids. The ratios of unsaturated/saturated fatty acids in microsomal lipids highly correlated with the eta values obtained for the combined group of fetal and adult human livers, suggesting that the developmental increase in degree of unsaturation of the microsomal lipids is a major determinant of the increased fluidity of adult as compared with fetal liver microsomes. These differences in fluidity and lipid composition between fetal and adult human liver microsomes may be a critical factor in the regulation of hepatic microsomal drug and carcinogen metabolizing enzyme activity, and could so determine the extent of toxicity and teratogenicity of drugs and/or their metabolites in the developing human fetus.