Molecular basis of cholesterol efflux via ABCG subfamily transporters

The ABCG1 homodimer (G1) and ABCG5–ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)–binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters.

Pengaruh Konsumsi Serat Pangan Barley Pada Metabolisme Lipid

Barley adalah tanaman serealia yang mempunyai serat pangan beta glukan dengan kandungan yang cukup tinggi. Beta glukan sebagai komponen dietary fiber mampu meningkatkan ekskresi asam empedu atau neutral sterols, meningkatkan katabolisme low-density lipoprotein cholesterol (LDL), dan mengurangi absorpsi lemak. Azoxymethane (AOM) merupakan senyawa karsinogen yang dapat menyebabkan gangguan metabolisme lipid dalam tubuh. Gangguan metabolisme lipid akan mengakibatkan kenaikan konsentrasi TG, TC, dan LDL serta menurunkan konsentrasi HDL. Adanya konsumsi dietary fiber barley dapat memberikan pengaruh positif atau efek pemulihan terhadap objek percobaan yang telah mengalami gangguan metabolisme lipid tersebut. Azoxymethane (AOM) merupakan senyawa karsinogen yang dapat menyebabkan gangguan metabolisme lipid dalam tubuh. Gangguan metabolisme lipid akan mengakibatkan kenaikan konsentrasi TG, TC, dan LDL serta menurunkan konsentrasi HDL. Adanya konsumsi dietary fiber barley dapat memberikan pengaruh positif atau efek pemulihan terhadap objek percobaan yang telah mengalami gangguan metabolisme lipid tersebut. Kata kunci: barley, serat pangan, lipid

Neutral Sterols of Cephalic Glands of Stingless Bees and Their Correlation with Sterols from Pollen

Sterols are essential molecules in the membrane lipid composition and precursors of important sterol hormones that regulate many developmental processes. Insects are unable to synthesize sterolsde novoand, thus, all phytophagous insects depend on an exogenous source of sterols for growth, development, and reproduction. The sterol requirements of social bees are not fully known due to the fact that there is no well-defined diet available throughout the year with regard to floral resources. Our study aimed to characterize the sterols present in pollen stored inMelipona marginataandMelipona scutellariscolonies, as well as evaluating their presence in the mandibular, hypopharyngeal, and cephalic salivary gland secretions. We analyzed the chemical composition of pollen stored in the colonies and the composition of the cephalic glands of workers in three adult functional phases (newly emerged, nurses, and foragers) by gas chromatography and mass spectrometry. The results showed that the pollen analyzed contained campesterol, stigmasterol, sitosterol, isofucosterol, lanosterol, and small amounts of cholesterol. The glands showed the same compounds found in the pollen analyzed, except lanosterol that was not found inM. scutellarisglands. Surprisingly, cholesterol was found in some glands with relative ratios greater than those found in pollen.

The fat and protein fractions of freshwater clam (Corbicula fluminea) extract reduce serum cholesterol and enhance bile acid biosynthesis and sterol excretion in hypercholesterolaemic rats fed a high-cholesterol diet

We investigated whether the fat and protein fractions of freshwater clam (Corbicula fluminea) extract (FCE) could ameliorate hypercholesterolaemia in rats fed a high-cholesterol diet. We also explored the mechanism and the components that exert the hypocholesterolaemic effect of FCE. The doses of the fat and protein fractions were equivalent to those in 30 % FCE. The fat and protein fractions of FCE, two major components of FCE, significantly reduced the serum and hepatic cholesterol levels. The fat fraction more strongly reduced serum cholesterol levels than the same level of total FCE. The excretion of faecal neutral sterols increased in rats fed the total the FCE and the fat fraction of FCE. On the other hand, faecal bile acid levels were greater in rats fed the total FCE and the fat and protein fractions of FCE than in control animals. The hepatic gene expression of ATP-binding cassette transporter G5 and cholesterol 7α-hydroxylase was up-regulated by the administration of the total FCE and both the fat and protein fractions of FCE. These results showed that the fat and protein fractions of FCE had hypocholesterolaemic properties, and that these effects were greater with the fat fraction than with the protein fraction. The present study indicates that FCE exerts its hypocholesterolaemic effects through at least two different mechanisms, including enhanced excretion of neutral sterols and up-regulated biosynthesis of bile acids.