The influence of fatty acid unsaturation and physical properties of microsomal membrane phospholipids on UDP-glucuronyltransferase activity

Abstract

The relationship between lipid composition, the physical properties of microsomal phospholipids and the kinetics of liver UDP-glucuronyltransferase was studied in microsomes from guinea pigs supplied with a normal or a fat-free diet for 28 days. Fatty acid deficiency did not modify either the cholesterol/phospholipid molar ratio or the polar head group composition, but exclusively redistributed the unsaturated fatty acid pattern, by partially exchanging oleic for linoleic acid. This phenomenon accounts for the decrease of both rotational and translational mobilities of the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and pyrene respectively. When the thermotropic behaviour of the different systems was assessed, no transition temperature (gel-liquid-crystalline) between 10 and 40 degrees C was seen as a consequence of the lower degree of unsaturation, either in the microsomal membranes or in the total lipid or total phospholipid extracts from the treated animals. In spite of this, the polarization ratio of trans-parinaric acid and the fluorescence intensity of merocyanine 540 revealed that a significant lateral phase separation occurred at 20-22 degrees C in the extracted phospholipids, which was smoother in the total lipid fractions and in the native microsomal membranes. Fatty acid deficiency caused an upward shift of the midpoint temperature of the lateral phase separation. Furthermore, the phosphatidylcholine extracted from the 'normal' microsomes showed a lateral phase separation centred at a lower temperature than that extracted from 'fat-deficient' microsomes. In contrast, the Arrhenius plot of UDP-glucuronyltransferase from 'normal' microsomes exhibited a change in slope at a higher temperature than that from treated microsomes. These results would suggest that fatty acid deficiency in guinea-pig liver microsomes, while rigidizing the bulk lipids, would segregate the most unsaturated phosphatidylcholine molecules towards the UDP-glucuronyltransferase microenvironment, in accordance with our previous results with cholesterol incorporation [Castuma & Brenner (1986) Biochemistry 25, 4733-4738].

Molecular species of phosphoglycerides in liver microsomes of rats fed a fat‐free diet

“…Appreciable amounts of the nonessential fatty acid 20:3n-9, which is present only in trace amounts in EFA-sufficient animals, appear as a consequence of EFA or fat-free diets in rat (10,12,13) but not in guinea pig liver microsomes (14)(15)(16)(17).…”

“…Several studies using spectroscopic methods such as fluorescence (14,16,17) or electron spin resonance (3,6,15) have indicated that EFA or fat-free diets affect the physical properties of different membranes, such as guinea pig liver microsomes (14)(15)(16)(17) or piglet jejunum brush border membranes (3,6). This is attributed to changes in the fatty acid composition of membrane lipids, since no changes are observed either in the phospholipid class distribution or in the relative content of cholesterol, phospholipid, and protein.…”

“…EFA-deficient and fat-free diets modify the fatty acid composition of several membranes in different species (3,(10)(11)(12)(13)(14)(15)(16)(17).…”

Vanadium: A Modifier of Drug-Metabolizing Enzyme Patterns and Its Critical Role in Cellular Proliferation in Transplantable Murine Lymphoma

“…UDPGT activity is de pendent on the proper association of monomeric polypep tides and is sensitive to changes in protein-lipid interac tion. Since vanadium has been reported to induce lipid peroxidation in different organs [21,27], the increase in UDPGT activity in groups 9 and 10 may be due to an attempt made by the cells to combat the damage inflicted due to the breakdown of membrane phospholipids [28]. The sharp decline in UDPGT activity after the 14th day with the two higher doses and to a lesser extent with the next two doses indicates tumour promotion leading to decreased survival of the host.…”

Effect of Dietary Fat on Rat Liver Microsomal Enzymes and Lipid Composition.

“…Changes in the lipid composition of microsomal membrane are known to affect the structure and dynamics of the bilayer and to produce diverse effects on the kinetic behavior of intrinsic proteins of the membrane [29][30][31][32][33][34]. The influence of quality and quantity of dietary fat on mixed-function oxidases has been studied extensively [35][36][37][38][39][40].…”