Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LIPIDS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed1993

Sensitivity of phospholipase C (Bacillus cereus) activity to lipid packing in sonicated lipid mixtures.

We have recently demonstrated that phospholipase C (PLC) activity on membranes decreases in the presence of membrane-active peptides such as alamethicin, gramicidin S, and melittin [Rao, N. M. (1992) Biochem. Biophys. Res. Commun. 182, 682-688]. Since these peptides affect lipid packing in the membrane and induce nonbilayer phases depending on the lipid composition, we tested for the sensitivity of PLC activity to lipid packing. We monitored PLC activities on four lipid systems which demonstrate a transition from the bilayer to the nonbilayer phase as a function of one of the components. The four model systems are (1) dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE); (2) DOPE, DOPC, and cholesterol; (3) DOPE and lysophosphatidylcholine; and (4) DOPC and gramicidin D. On all four lipid systems, the PLC activity was high for lipid in the bilayer phase and decreased as the phase changed to the nonbilayer phase. The phase changes were also monitored in PLC assay conditions on the four model systems by 31P NMR to confirm the observations made with PLC. These results suggest that the lipid in bilayer and nonbilayer phases was differentially susceptible to PLC; hence, PLC activity may be used to monitor isothermal phase transitions at physiological conditions.

Bacillus cereus↗
PubMed1986

Relationship between three-dimensional arrays of "lipidic particles" and bicontinuous cubic lipid phases.

Several lipid-water mixtures form phases that give rise to freeze-fracture replicas exhibiting three-dimensional regular arrays of closely packed globular elements, often called "lipidic particles". These phases have often been poorly classified with respect to long-range organization and symmetry and have in most cases been asserted to be built up by closed lipid aggregates, such as reversed micelles. However, studies of phases giving rise to the above-mentioned freeze-fracture replicas, with X-ray diffraction and the nuclear magnetic resonance pulsed field gradient diffusion technique, have revealed that they are cubic liquid-crystalline phases and with one exception bicontinuous phases, i.e., cubic phases in which both the hydrocarbon and the water regions are continuous. Up to now the only known exception is a cubic phase composed of closed rod-shaped micelles of the normal type. Thus it is not possible to decide from a freeze-fracture image of a cubic phase, showing three-dimensional arrays of "lipidic particles", if the phase is bicontinuous or composed of closed lipid aggregates. Hitherto, it has not been shown that a biological membrane lipid-water system is able to form a cubic liquid-crystalline phase consisting of reversed micelles. The existence of such a phase is also improbable considering the location in the phase diagrams of cubic phases formed by biological membrane lipid-water systems.

Diglycerides↗
PubMed2002

The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid lowering therapy?

Diabetic maculopathy is a common complication of diabetes mellitus, characterised by macular oedema and frequently accompanied by lipid exudation. It is the major cause of loss of vision from diabetic retinopathy. There is some evidence to implicate serum lipids in exudative maculopathy; cross-sectional studies suggest that higher serum lipid levels are found in patients with macular exudates, and prospective studies have shown an increased risk of exudative maculopathy if baseline cholesterol is higher. The treatment for diabetic maculopathy is laser photocoagulation of the pigment epithelium. With the advent of systemic lipid lowering therapy over the last decade, there may be potential for medical therapy also. There is some anecdotal evidence of the effect of lipid lowering agents (particularly statins) in reducing exudate, and a number of studies have shown that lipid lowering therapy may reduce macular exudates, but numbers in these trials are small. A randomised controlled trial is now required to investigate whether the use of systemic lipid lowering therapy is of benefit in patients with exudative maculopathy, even in the absence of dyslipidaemia.

Diabetic Retinopathy↗
PubMed1982

Lipid metabolism in riboflavin-deficient rats. 1. Effect of dietary lipids on riboflavin status and fatty acid profiles.

1. The increase in activation coefficient (stimulated: basal activity) of erythrocyte NAD(P)H2: glutathione oxidoreductase (EC 1.6.4.2) and reduction in hepatic flavin concentration which occurred in riboflavin-deficient weanling rats were not markedly or consistently affected by differences in the concentration of lipid in the diet nor by differences in the total proportion of saturated or polyunsaturated fatty acids in the dietary lipid. 2. Their gain in body-weight was, however, reduced when the dietary lipid concentration was increased from 30 to 200 g/kg and liver: body-weight and hepatic triglyceride content were correspondingly increased, suggesting a functionally-deleterious effect of high fat intake in the deficient animals. This was especially severe when the diets contained cottonseed oil, which appeared to be toxic for the deficient animals. 3. Comparisons between fatty acid profiles of hepatic phospholipids of deficient, pair-fed and ad lib,-fed control animals indicated that the increase in proportion of 18:2 omega 6 and the decrease in proportion of 20:4 omega 6 observed in deficient animals were due specifically to riboflavin deficiency, whereas certain other changes were probably caused by inanition. The changes in 18:2 omega 6 and 20:4 omega 6 were observed at both low and high levels of lipid intake and at both low and high levels of dietary lipid polyunsaturation. Similar changes in fatty acid profiles were observed in renal, erythrocyte membrane, and plasma phospholipids, but were not seen in cardiac phospholipids, 4. A consistent increase in proportion of 18:2 omega 6 was also observed in the hepatic triglycerides, together with a decrease in proportion of 16:0. 5. It is concluded that acute riboflavin deficiency affects lipid metabolism in a characteristic manner, probably by interfering with beta-oxidation of fatty acids, but that diets of high lipid content do not significantly increase the extent of flavin depletion.

Animals↗
PubMed2004

Lipid levels and the use of lipid-lowering agents in England and Scotland.

OBJECTIVE: Preventing cardiovascular events with lipid-lowering drugs has been established in several trials reported since 1994. Consequently national guidelines recommend statins for those with established cardiovascular disease (CVD) and those at high risk of developing CVD. We evaluated blood lipid levels, and compare treatment and control of dyslipidaemia in English and Scottish adults with national recommendations for lipid lowering. DESIGN AND METHODS: In 1998 the nationally-representative Health Survey for England and the Scottish Health Survey included valid cholesterol results for 9631 (England) and 6065 (Scotland) adults aged 16-74. Mean blood levels of total, high-density lipoproteins (HDL-), and total:HDL-cholesterol ratio; prevalence of elevated total cholesterol levels, and total:HDL-cholesterol ratios; prevalence of use of lipid-lowering agents in high risk subgroups; and lipid levels of those on treatment were calculated. RESULTS: Levels of dyslipidaemia, treatment and control were not significantly different between Scotland and England. Combining these data, mean total cholesterol levels were 5.43 and 5.48 mmol/l in men and women respectively; and mean HDL-cholesterol levels were 1.29 and 1.56 mmol/l. Overall 64.6% of adults had a total cholesterol > or =5 mmol/l, 24.6% had a total:HDL ratio > or =5 and 2.3% reported taking lipid-lowering drugs. Treatment rates among those with a total cholesterol >5 mmol/l and a history of coronary heart disease or stroke, hypertension, or diabetes, were 27.3%, 15.4% and 17.8% respectively, and control rates (total cholesterol <5 mmol/l) among those treated were 45.3%, 38.5% and 32.7%. CONCLUSIONS: Low treatment rates with lipid-lowering drugs existed overall, among high-risk patients suitable for primary prevention, and among those with established cardiovascular disease.

Adolescent↗
PubMed2006

Association of total cholesterol versus other serum lipid parameters with the short-term prediction of cardiovascular outcomes: Tehran Lipid and Glucose Study.

OBJECTIVE: The aim of this study was to evaluate and compare the role of lipid markers including total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol with lipid indices (total/HDL cholesterol, LDL-cholesterol/HDL-cholesterol and non-HDL-cholesterol) as predictors of cardiovascular outcomes in adults over 30 years. RESEARCH DESIGN AND METHOD: In a nested case-control study, 207 cardiovascular events among participants of the Tehran Lipid and Glucose Study (TLGS) were documented during 3 years of follow-up. Those cases that were free of cardiovascular disease at baseline (132 subjects) were matched to 264 controls for age and sex. In all subjects, demographic and clinical data including blood pressure and anthropometric measurements as well as serum lipids, fasting and 2-h plasma glucose were obtained from the database of the TLGS. We estimated the relative risk for each lipid parameter in a multiple stepwise regression model after adjustment for family history of premature coronary heart disease, smoking, systolic and diastolic blood pressure, fasting and 2-h plasma glucose and waist-to-hip ratio. RESULTS: The relative risks associated with an increase of approximately 1 SD of independent lipid predictors in the multivariate model were as follows: total cholesterol, 1.6 (1.2-2.1), SD=1.3 mmol/l; LDL-cholesterol 1.5 (1.1-2.0), SD=1 mmol/l; non-HDL-cholesterol 1.6 (1.2-2.1), SD=1.2 mmol/l and cholesterol/HDL-cholesterol 1.5 (1.1-2.0), SD=1.8. Comparison of these four independent variables with receiver-operating characteristic curve analysis showed no significant difference in their predictive power for cardiovascular outcome. There was no association between HDL-cholesterol, triglyceride and LDL/HDL cholesterol and cardiovascular disease outcomes in multivariate analysis. CONCLUSION: It seems that for short-term prediction of cardiovascular disease outcome, serum total cholesterol is the preferred lipid parameter to measure in the Iranian population.

Adult↗
PubMed1976

The binding of lipid to the lipid-free adenosine triphosphatase protein of sarcoplasmic reticulum.

Dinitrophenylated dipalmitoyl phosphatidylethanolamine and its lyso derivative have been shown to bind to the lipid-free ATPase protein derived from the sarcoplasmic reticulum. The binding of these lipids is accompained by the quenching of up to 95% of the tryptophyl fluorescence of the protein. This effect is reversed by 9-10 mM deoxycholate. The solubility of the lipid-free ATPase protein in the absence of deoxycholate and the solubility of submillimolar concentrations of the dinitrophenylated monopalmitoyl phosphatidylethanolamine anion in aqueous media allowed binding experiments using this lipid ligand to be carried out in a simple buffer system. It is shown that in the case of this lipid the initial phase of the binding process displays an apparent positive co-operatively. Data from the second phase in the saturation of the protein with this lipid is consistent with binding to independent, equivalent, non-interacting sites with a microscopic (intrinsic) association constant of 1.63 x 10(6) M-1, the fluorescence being quenched in the geometric fashion. Altogether a total of about 15 molecules of this lipid may be bound by the protein.

Adenosine Triphosphatases↗
PubMed1999

The effects of short term lipid infusion on plasma and hepatic bile lipids in humans.

BACKGROUND: Patients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder. AIMS: To determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy. METHODS: In eight patients undergoing the above surgical procedure, the time at which effects of the interrupted enterohepatic circulation were minimal was determined. Twenty two cholesterol gallstone patients with bile fistula were then randomised to receive an infusion of a lipid emulsion containing either long chain triglycerides or a mixture of long and medium chain triglycerides. RESULTS: Lipid infusion resulted in a significant increase in plasma levels of triglycerides and phospholipids. Both lipid emulsions caused an increase in hepatic biliary cholesterol level and cholesterol saturation index, but this effect was more pronounced with medium chain triglycerides. The fatty acid composition of biliary phospholipids showed a significant enrichment of linoleic acid by both lipid infusions. CONCLUSIONS: Infusion of triglycerides causes lithogenic changes in hepatic bile composition in humans, the lithogenic effect of infusion of medium chain triglycerides being more pronounced than that of long chain triglycerides. This effect, coupled with gall bladder stasis, may be responsible for the increased risk of biliary sludge and gallstone formation in patients on long term lipid infusion.

Adult↗
PubMed1989

Influence of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice.

The effects of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice have been investigated using a versatile procedure for encapsulating doxorubicin inside liposomes. In this procedure, vesicles exhibiting transmembrane pH gradients (acidic inside) were employed to achieve drug trapping efficiencies in excess of 98%. Drug-to-lipid ratios as high as 0.3:1 (wt:wt) could be obtained in a manner that is relatively independent of lipid composition and vesicle size. Egg phosphatidylcholine (EPC)/cholesterol (55:45; mol/mol) vesicles sized through filters with a 200-nm pore size and loaded employing transmembrane pH gradients to achieve a doxorubicin-to-lipid ratio of 0.3:1 (wt/wt) increased the LD50 of free drug by approximately twofold. Removing cholesterol or decreasing the drug-to-lipid ratio in EPC/cholesterol preparations led to significant decreases in the LD50 of liposomal doxorubicin whereas, the LD50 increased 4- to 6-fold when distearoylphosphatidylcholine was substituted for EPC. The results suggest that the stability of liposomally entrapped doxorubicin in the circulation is an important factor in the toxicity of this drug in liposomal form. In contrast, the antitumor activity of liposomal doxorubicin is not influenced dramatically by alterations in lipid composition. Liposomal doxorubicin preparations of EPC, EPC/cholesterol (55:45; mol:mol), EPC/egg phosphatidylglycerol (EPG)/cholesterol (27.5:27.5:45; mol:mol), and distearoylphosphatidylcholine/cholesterol (55:45; mol:mol) all demonstrated similar efficacy to that of free drug when given at doses of 20 mg/kg and below. Higher dose levels of the less toxic formulations could be administered, leading to enhanced increases in life span (ILS) values. Variations in vesicle size, however, strongly influenced the antitumor activity of liposomal doxorubicin. At a dose of 20 mg/kg, large EPC/cholesterol systems are significantly less effective than free drug (with ILS values of 65% and 145%, respectively). In contrast, small systems sized through filters with a 100-nm pore size are more effective than free drug, resulting in an ILS of 375% and a 30% long term (greater than 60 days) survival rate when administered at a dose of 20 mg/kg. Similar size-dependent effects are observed for distearoylphosphatidylcholine/cholesterol systems.

Animals↗
PubMed1994

Quantitative determination of urinary lipid metabolites by high pressure liquid chromatography as indicators of menadione-induced in vivo lipid peroxidation.

The one- and two-electron-reduction reactions of menadione result in the generation of reactive oxygen species which are believed to mediate the cytotoxicity of this xenobiotic. The induction of lipid peroxidation in liver and isolated hepatocytes occurs in response to the menadione-mediated formation of reactive oxygen species. However, studies on the effects of menadione on the urinary excretion of lipid metabolites have not been conducted. The effect of a single oral dose of 60 mg menadione/kg to rats on the urinary excretion of the lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) has been examined over 48 h post-treatment. The urinary metabolites were identified by gas chromatography-mass spectrometry and quantitated by high pressure liquid chromatography. Time-dependent increases in the urinary excretion of the four metabolites were observed after menadione administration. Over the 48 h of the study, the menadione-induced urinary excretion of MDA, FA, ACT, and ACON increased by approximately 1.5-, 2.0-, 1.7-, and 3.2-fold, respectively, relative to control animals. The data were expressed in nmoles/kg body weight/4.5 h. The results clearly demonstrate that menadione increases the urinary excretion of four lipid metabolites. These metabolites may have widespread applicability as biomarkers of altered lipid metabolism in disease states and exposure to environmental pollutants/xenobiotics which induce enhanced lipid peroxidation. The non-invasive methods offer advantages over most other methods for assessing oxidative stress in vivo.

Animals↗
PubMed2000

Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis.

An animal model of chronic fluorosis was produced by subjecting Wistar rats to high doses of fluoride in drinking water for a prolonged period. Phospholipid and neutral lipid contents in rat kidney were then analyzed by high-performance liquid chromatography (HPLC), and fatty acid compositions from individual phospholipids were measured by gas chromatography. Lipid peroxidation was detected by the thiobarbituric-acid-reactive substance assay. Results showed that the total phospholipid content significantly decreased in the kidney of the rats treated with high doses of fluoride and the main species influenced were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Decreased proportions of polyunsaturated fatty acids were observed in PE and PC in kidney of fluoride-treated animals compared to controls. No changes could be detected in the amounts of cholesterol and dolichol in kidneys between the rats treated with fluoride and controls. A significant decrease of ubiquinone in rat kidney was observed in the groups treated with excessive fluoride. High levels of lipid peroxidation were detected in kidney of the rats with fluorosis. It is plausible that the specific modification of lipid composition results from lipid peroxidation. The oxidative stress and modification of cellular membrane lipids may be involved in the pathogenesis of chronic fluorosis and provide a possible explanation for the gross system damage observed in the body, especially in soft tissues and organs.

Animals↗
PubMed2006

Lipid nitration and formation of lipid-protein adducts: biological insights.

Lipid-protein adducts are formed during oxidative and nitrative stress conditions associated with increasing lipid and protein oxidation and nitration. The focus of this review is the analysis of interactions between oxidative-modified lipids and proteins and how lipid nitration can modulate lipid-protein adducts formation. For this, two biologically-relevant models will be analysed: a) human low density lipoprotein, whose oxidation is involved in the early steps of atherogenesis, and b) alpha-synuclein/lipid membranes system, where lipid-protein adducts are being associated with the develop of Parkinson disease and other synucleinopathies.

Humans↗
PubMed1986

The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis.

Concentrations of plasma triglycerides, cholesterol, total lipids and lipid peroxides in patients with atherosclerotic lesions of peripheral arteries, who were divided into groups according to the extent and intensity of the lesions, were estimated, as well as lipid peroxide levels in the arterial wall. Statistically highly significant increases of the estimated compounds were found in all groups in comparison with the controls. The existence of a positive correlation between the lipid peroxide concentration and other investigated components in plasma and between the lipid peroxide level in plasma and in the arterial wall was found. Possible mechanisms for lipid peroxide involvement in the process of originating atherosclerotic lesions are discussed.

Adult↗
PubMed1995

Adriamycin-induced hepatic and myocardial lipid peroxidation and DNA damage, and enhanced excretion of urinary lipid metabolites in rats.

Adriamycin produces clinically useful responses in a variety of human cancers including lymphomas, leukemias, and solid tumors. However, the toxicity of adriamycin has limited its usefulness. Iron-catalyzed free radical reactions as the peroxidation of membrane lipids, inactivation of critical enzymes, and the inhibition of DNA, RNA and protein synthesis in heart, liver and kidney have been implicated in the toxicity of adriamycin. In order to further assess the role of oxidative stress in the toxicity of adriamycin, the effects of adriamycin were examined on the urinary excretion of lipid metabolites at 0, 6, 12, 24, 48 and 72 h post-treatment, and on myocardial and hepatic lipid peroxidation and nuclear DNA single strand breaks at 24 h post-treatment following single oral and intravenous (i.v.) doses of 10 mg/kg adriamycin. Urinary malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) excretion was significantly increased at all time points examined. Following the oral administration of adriamycin, maximum excretion of MDA, FA, ACT and ACON of 6.2-, 2.7-, 3.7- and 2.2-fold relative to control values, respectively, occurred 24 h after treatment. However, following the i.v. administration of adriamycin, greatest increases in excretion of MDA, FA and ACT reaching 6.9-, 3.3- and 6.3-fold relative to control values, respectively, were observed 6 h after treatment, while the greatest increase in ACON excretion of 4.2-fold relative to control values occurred 12 h post-treatment. Following oral and i.v. administration of adriamycin, significant increases were observed in myocardial and hepatic lipid peroxidation in mitochondrial and microsomal membranes, and myocardial and hepatic nuclei DNA single strand breaks 24 h after treatment. The results indicate that adriamycin administration induces myocardial and hepatic lipid peroxidation which may be responsible for enhanced excretion of urinary lipid metabolites as a result of membrane damage, and also induces enhanced DNA damage. These effects may be due to adriamycin-induced production of reactive oxygen species.

Acetaldehyde↗
PubMed2004

Effect of sodium molybdate on the status of lipids, lipid peroxidation and antioxidant systems in alloxan-induced diabetic rats.

BACKGROUND: Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multi-factorial. METHODS: The lipid peroxidation (LPO) and antioxidant status were investigated in hemolysate, liver and kidney in alloxan-induced diabetic rats and the effect of molybdate supplementation on antioxidant defense systems. RESULTS: Diabetic rats exhibited an increase in the levels of lipids, lipid peroxidation and decrease in antioxidant status when compared to control rats. Oral administration of molybdate to diabetic rats for 30 days significantly reduced the levels of lipids like cholesterol, triglycerides, phospholipids and lipid peroxidation whereas increased the activities of antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). CONCLUSION: Molybdate prevents oxidation of lipids and protects antioxidant systems in experimental diabetic rats, and thus, may be useful for the prevention or early treatment of diabetic mellitus.

Animals↗
PubMed2000

The interaction between lipid derivatives of colchicine and tubulin: consequences of the interaction of the alkaloid with lipid membranes.

Colchicine is a potent antimitotic poison which is well known to prevent microtubule assembly by binding tubulin very tightly. Colchicine also possesses anti-inflammatory properties which are not well understood yet. Here we show that colchicine tightly interacts with lipid layers. The physical and biological properties of three different lipid derivatives of colchicine are investigated parallel to those of membrane lipids in the presence of colchicine. Upon insertion in the fatty alkyl chains, colchicine rigidifies the lipid monolayers in a fluid phase and fluidifies rigid monolayers. Similarly X-ray diffraction data show that lecithin-water phases are destabilized by colchicine. In addition, an unexpectedly drastic enhancement of the photoisomerization rate of colchicine into lumicolchicine in the lipid environment is observed and further supports insertion of the alkaloid in membranes. Finally the interaction of colchicine with lipids makes the drug inaccessible to tubulin. The possible in vivo significance of these results is discussed.

Colchicine↗
PubMed1999

Lipid-induced conformation and lipid-binding properties of cytolytic and antimicrobial peptides: determination and biological specificity.

While antimicrobial and cytolytic peptides exert their effects on cells largely by interacting with the lipid bilayers of their membranes, the influence of the cell membrane lipid composition on the specificity of these peptides towards a given organism is not yet understood. The lack of experimental model systems that mimic the complexity of natural cell membranes has hampered efforts to establish a direct correlation between the induced conformation of these peptides upon binding to cell membranes and their biological specificities. Nevertheless, studies using model membranes reconstituted from lipids and a few membrane-associated proteins, combined with spectroscopic techniques (i.e. circular dichroism, fluorescence spectroscopy, Fourier transform infra red spectroscopy, etc.), have provided information on specific structure-function relationships of peptide-membrane interactions at the molecular level. Reversed phase-high performance chromatography (RP-HPLC) and surface plasmon resonance (SPR) are emerging techniques for the study of the dynamics of the interactions between cytolytic and antimicrobial peptides and lipid surfaces. Thus, the immobilization of lipid moieties onto RP-HPLC sorbent now allows the investigation of peptide conformational transition upon interaction with membrane surfaces, while SPR allows the observation of the time course of peptide binding to membrane surfaces. Such studies have clearly demonstrated the complexity of peptide-membrane interactions in terms of the mutual changes in peptide binding, conformation, orientation, and lipid organization, and have, to a certain extent, allowed correlations to be drawn between peptide conformational properties and lytic activity.

Animals↗
PubMed2002

How the lipid-free structure of the N-terminal truncated human apoA-I converts to the lipid-bound form: new insights from NMR and X-ray structural comparison.

The X-ray structure of the N-terminal truncated human apoA-I [Borhani et al., Proc. Natl. Acad. Sci. USA 94 (1997) 12291] and the NMR structure of intact human apoA-I [Okon et al., FEBS Lett. 517 (2002) 139] found similar repeating helices. The crystal structure is a twisted circular four-helix bundle, consisting of four molecules of apoA-I(44-243), where four copies of the lecithin:cholesterol acyltransferase (LCAT)-activating domains are located outside the ring structure, while the aromatic-rich strong lipid-binding domains are inside. This architecture suggests a lipid-binding mechanism that lipids directly enter the hole of the crystal structure. Indeed, four copies of Trp50 and Trp72 are exposed and oriented toward the center of the ring, initiating lipid binding. This is followed by the inside-out rotations of the terminal helices to make a belt with all the hydrophobic faces of the helices facing inward. Such lipid-binding induced rotations have an impact on the conformation of the lipid-free form. Indeed, the structure of residues 78-81 changes from helical (free) to disordered (bound) while the structure of residues 221-227 changes from extended to helical.

Apolipoprotein A-I↗