| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men Hargreaves, A. D., R. L. Logan, et al. (1992), Atherosclerosis 94(1): 61-9. Abstract: The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose and glucose response to OGTT were higher in 1988-89 than in 1976. In contrast, insulin levels did not differ between the initial and follow-up study either before or after the glucose load. Body mass indices increased, except triceps skinfold. Changing patterns in both fasting and OGTT insulin or glucose levels in individuals were related to changes in bodyweight or in subscapular skinfolds. Modifications in serum total and HDL cholesterol were related to changes in fasting insulin and insulin area, respectively, but not to glucose data. Eleven men developed clinical CHD. Neither glucose nor insulin measures obtained in 1976 differed between those with and without CHD. Weight-height index and abdominal skin-folds were higher in those with CHD. HDL cholesterol was significantly lower (P less than 0.05). Abdominal skin-fold but not body mass index remained significant when adjusted for HDL cholesterol. This small study confirms the importance of central obesity and low HDL cholesterol but failed to identify insulin as a risk factor for CHD in this Scottish population. |
| Glucose-cholesterol interaction magnifies coronary heart disease risk for hypertensive patients Cohen, H. W., S. M. Hailpern, et al. (2004), Hypertension 43(5): 983-7. Abstract: Elevated cholesterol and glucose are known independent risk factors for coronary heart disease. This study examines whether an adverse synergistic interaction of cholesterol and glucose magnifies coronary heart disease risk among treated hypertensive patients. Subjects were hypertensive patients (n=6672) in a worksite treatment program, with entry fasting glucose <6.99 mmol/L (126 mg/dL) and total cholesterol <6.72 mmol/L (260 mg/dL) observed for mean 5.6+/-4.5 years follow-up (range 0.5 to 21.7 years). Outcome events were incident hospitalization or death due to coronary heart disease. Cox proportional hazard models were constructed for the whole sample to assess interaction and then stratified by fasting glucose categories with thresholds defined either at impaired fasting glucose (> or =6.11 mmol/L 110 mg/dL) or upper quartile (> or =5.72 mmol/L 103 mg/dL). An interaction product term of total cholesterol and fasting glucose as continuous variables significantly (P=0.009) improved a Cox proportional hazards model, adjusting for total cholesterol, fasting glucose, and other coronary heart disease risk factors. Adjusted hazard ratios for 3 upper total cholesterol categories (with total cholesterol <5.17 mmol/L 200 mg/dL as reference) in the higher fasting glucose stratum were more than double the corresponding hazard ratios in the lower stratum, whether using impaired fasting glucose or upper quartile fasting glucose as the cut point. These results suggest that an adverse synergistic interaction between glucose and cholesterol magnifies coronary heart disease risk associated with total cholesterol among hypertensive patients, raising the possibility that coronary heart disease prevention might be enhanced if cholesterol intervention criteria were modified by glucose status. |
| Glucosyl hesperidin improves serum cholesterol composition and inhibits hypertrophy in vasculature Ohtsuki, K., A. Abe, et al. (2003), J Nutr Sci Vitaminol (Tokyo) 49(6): 447-50. Abstract: Long-term administration of hesperidin (HES) or glucosyl hesperidin (GHES), a water-soluble analogue of HES, brings about an antihypertensive effect on spontaneously hypertensive rats (SHR). In the present study, we investigated the effects of long-term administration of HES and GHES (corresponding to 30 mg/d/kg body weight) on serum lipid concentration and morphology of vasculature. Serum HDL cholesterol increased in both SHR and Wistar-Kyoto rats (WKY) fed a HES- or GHES-containing diet for 25 wk. Simultaneously, GHES administration reduced the vascular diameter and media-intimal cross-sectional area of the abdominal aorta in SHR. These results suggest that HES as well as GHES improves serum cholesterol composition and that GHES inhibits hypertrophy in vasculature as well. |
| Glucosylceramidase mass and subcellular localization are modulated by cholesterol in Niemann-Pick disease type C Salvioli, R., S. Scarpa, et al. (2004), J Biol Chem 279(17): 17674-80. Abstract: Niemann-Pick disease type C (NPC) is characterized by the accumulation of cholesterol and sphingolipids in the late endosomal/lysosomal compartment. The mechanism by which the concentration of sphingolipids such as glucosylceramide is increased in this disease is poorly understood. We have found that, in NPC fibroblasts, the cholesterol storage affects the stability of glucosylceramidase (GCase), decreasing its mass and activity; a reduction of cholesterol raises the level of GCase to nearly normal values. GCase is activated and stabilized by saposin C (Sap C) and anionic phospholipids. Here we show by immunofluorescence microscopy that in normal fibroblasts, GCase, Sap C, and lysobisphosphatidic acid (LBPA), the most abundant anionic phospholipid in the endolysosomal system, reside in the same intracellular vesicular structures. In contrast, the colocalization of GCase, Sap C, and LBPA is markedly impaired in NPC fibroblasts but can be re-established by cholesterol depletion. These data show for the first time that the level of cholesterol modulates the interaction of GCase with its protein and lipid activators, namely Sap C and LBPA, regulating the GCase activity and stability. |
| Glutathione and bile acid synthesis. Effect of GSH content of HepG2 cells on the activity and mRNA levels of cholesterol 7 alpha-hydroxylase Hassan, A. S., D. Bunick, et al. (1992), Biochem Pharmacol 44(7): 1475-7. Abstract: Cholesterol 7 alpha-hydroxylase (CH-7 alpha) activity in HepG2 cells depleted of glutathione (GSH) was reduced significantly (P < 0.05) compared to that in untreated controls. Northern blot analysis of poly A+ mRNA isolated from GSH-depleted and control HepG2 cells showed that there was a reduction in mRNA for CH-7 alpha in treated HepG2 cells that was commensurate with the reduction in CH-7 alpha activity. The fact that total RNA, rRNA, and mRNA for beta fibrinogen were unaltered by the depletion of GSH suggests that the change in steady-state CH-7 alpha mRNA content is specifically sensitive to GSH content. This observation represents the first demonstration, for human liver cells, that there is an interaction between GSH levels and the regulation of CH-7 alpha mRNA levels. |
| Gly15Gly polymorphism within the human adipocyte-specific apM-1gene but not Tyr111His polymorphism is associated with higher levels of cholesterol and LDL-cholesterol in caucasian patients with type 2 diabetes Zietz, B., N. Barth, et al. (2001), Exp Clin Endocrinol Diabetes 109(6): 320-5. Abstract: The recently described mutations within the human adipocyte-specific apM-1 gene might play a role in the pathogenesis of obesity, type 2 diabetes and related metabolic disorders. DESIGN: Frequency of apM-1 gene polymorphisms and their association with metabolic parameters was evaluated in a population-based sample of 556 type 2 (316 males / 240 females) diabetic patients. PCR-based RFLP analysis was performed in blood samples. The T --> G transition at nucleotide +45 within exon-2 Gly15Gly was detected with an allelic frequency of 0.91 for the wildtype allele and 0.09 for the mutated allele. The missense point mutation (TAC --> CAC) at nucleotide +331 within exon 3 Tyr111His was detected with an allelic frequency of 0.97 and 0.03, respectively. These frequencies did not differ from a non-diabetic cohort examined earlier. Concerning the Gly15Gly polymorphism, the TT-genotype was found in 457 (82.2%) and the TG-genotype in 99 (17.8%), concerning the Tyr111His polymorphism, TT-genotype was found in 525 (94.4) and TC-genotype in 31 (5.6%) of type 2 diabetic patients. In TG-genotype as compared to TT-genotype significantly more patients had LDL-serum levels in high LDL-classes (<150 mg/dl: 24.4% (TG) vs. 41.4% (TT), 150mg/dl to 190mg/dl: 40.0% (TG) vs. 33.9% (TT), >190 mg/l: 35.6% (TG) vs. 25.0% (TT); p = 0.010). No differences in serum levels of lipids were found in genotype-subgroups of the Tyr111His polymorphism. Thus, Gly15Gly polymorphism of apM-1 gene might play a role in dyslipidaemia in type 2 diabetic patients. |
| Glycaemic index as a determinant of serum HDL-cholesterol concentration Frost, G., A. A. Leeds, et al. (1999), Lancet 353(9158): 1045-8. Abstract: BACKGROUND: Diet influences the prevalence of coronary heart disease (CHD). Insulin sensitivity and concentrations of HDL cholesterol, two metabolic predictors of CHD, are also influenced by diet. Dietary carbohydrates with a high glycaemic index cause a high postprandial glucose and insulin response, and are associated with decreased insulin sensitivity and an increased risk of CHD. This study examined whether the glycaemic index of dietary carbohydrates is a determinant of serum HDL-cholesterol concentrations. METHOD: Dietary, anthropometric, and biochemical data from the 1986-87 Survey of British Adults (n=2200) were reanalysed by a multiple regression model, which examined the relation between serum total cholesterol, HDL-cholesterol, and calculated LDL-cholesterol concentrations and various dietary characteristics, including the type of carbohydrate, the glycaemic index, and fat intake. FINDINGS: Among the 1420 participants with complete data, there was a significant negative relation between serum HDL-cholesterol concentration and the glycaemic index of the diet for both men (regression coefficient -0.00724 95% CI -0.0101 to -0.00434, p=0.02) and women (-0.01326 -0.0162 to -0.0102, p<0.0001). No other significant relation was found with total cholesterol or LDL-cholesterol concentration or with any other dietary carbohydrate or fat constituent. INTERPRETATION: In a cross-sectional study of middle-aged adults, the glycaemic index of the diet was the only dietary variable significantly related to serum HDL-cholesterol concentration. Thus, the glycaemic index of the diet is a stronger predictor than dietary fat intake of serum HDL-cholesterol concentration. |
| Glycation of high-density lipoprotein does not increase its susceptibility to oxidation or diminish its cholesterol efflux capacity Rashduni, D. L., V. A. Rifici, et al. (1999), Metabolism 48(2): 139-43. Abstract: In vitro oxidation of high-density lipoprotein (HDL) diminishes its capacity to mediate cholesterol efflux from J774 macrophages. To investigate the possible role of HDL glycation in the increased atherosclerotic risk in diabetes, we studied the effects of in vitro glycation of HDL on its susceptibility to oxidation and capacity to mediate cholesterol efflux. HDL isolated from normal volunteers was incubated with 25 mmol/L glucose for 70 hours, resulting in 6.1% additional derivatization of apoproteins as determined by trinitrobenzene sulfonic acid (TNBS) reactivity. Unmodified HDL and glycated HDL (glyHDL) were tested for susceptibility to oxidation by incubation with various concentrations of copper and three assays of lipid oxidation. GlyHDL produced 51% to 64% less lipid peroxide than HDL as determined by reaction with xylenol orange (P <.02), indicating decreased susceptibility to oxidation. However, glycation of HDL did not result in significant changes in the formation of conjugated dienes or thiobarbituric acid-reactive substances (TBARS), two other indices of oxidation. To study cholesterol efflux, J774 macrophages were labeled with 3H-cholesterol followed by incubation with the various HDL preparations. HDL and glyHDL had a similar capacity to mediate efflux. The efflux mediated by oxidized HDL (oxHDL) and oxidized glyHDL was reduced to a similar extent compared with the efflux mediated by HDL and glyHDL. These data indicate that in vitro glycation of HDL does not increase its susceptibility to oxidation and does not diminish its capacity to mediate cholesterol efflux. |
| Glycemic index and serum high-density lipoprotein cholesterol concentration among us adults Ford, E. S. and S. Liu (2001), Arch Intern Med 161(4): 572-6. Abstract: BACKGROUND: Dietary glycemic index, an indicator of the ability of the carbohydrate to raise blood glucose levels, and glycemic load, the product of glycemic index and carbohydrate intake, have been positively related to risk of coronary heart disease. However, the relationships between glycemic index and glycemic load and high-density lipoprotein cholesterol (HDL-C) concentration in the US population are unknown. METHODS: Using data from 13 907 participants aged 20 years and older in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationships between glycemic index and glycemic load, which were determined from a food frequency questionnaire and HDL-C concentration. RESULTS: The age-adjusted mean HDL-C concentrations for increasing quintiles of glycemic index distribution were 1.38, 1.32, 1.30, 1.26, and 1.27 mmol/L (P<.001 for trend). (To convert millimoles per liter to milligrams per deciliter, divide by 0.0259.) After additional adjustment for sex, ethnicity, education, smoking status, body mass index, alcohol intake, physical activity, energy fraction from carbohydrates and fat, and total energy intake, the mean HDL-C concentrations for ascending quintiles of glycemic index were 1.36, 1.31, 1.30, 1.27, and 1.28 mmol/L (P<.001 for trend). Adjusting for the same covariates and considering glycemic index as a continuous variable, we found a change in HDL-C concentration of -0.06 mmol/L per 15-unit increase in glycemic index (P<.001). The multiple R(2) for the model was 0.23. Similarly, the multivariate-adjusted mean HDL-C concentrations for ascending quintiles of glycemic load distribution were 1.35, 1.31, 1.31, 1.30, and 1.26 mmol/L (P<.001 for linear trend). The inverse relationships between glycemic index and glycemic load and HDL-C persisted across all subgroups of participants categorized by sex or body mass index. CONCLUSIONS: These findings from a nationally representative sample of US adults suggest that high dietary glycemic index and high glycemic load are associated with a lower concentration of plasma HDL-C. |
| Glycerophospholipids and cholesterol composition of bile in bile-fistula rats treated with monensin Casu, A. and L. Camogliano (1990), Biochim Biophys Acta 1043(1): 113-5. Abstract: Data regarding the action of monensin on the concentrations of glycerophospholipids and cholesterol in bile of rats subjected to total biliary diversion for 3 h are reported. After monensin their concentration in bile drops significantly in the first 60 min collections with respect to the control. Differences seem to be produced between the rates of transport to the bile of glycerophospholipids and cholesterol, not sufficiently explained by the inhibition of bile salt uptake determined by monensin at the sinusoidal pole of the hepatocyte. |
| Glycoalkaloids selectively permeabilize cholesterol containing biomembranes Keukens, E. A., T. de Vrije, et al. (1996), Biochim Biophys Acta 1279(2): 243-50. Abstract: The effects of the glycoalkaloids alpha-solanine, alpha-chaconine and alpha-tomatine on different cell types were studied in order to investigate the membrane action of these compounds. Hemolysis of erythrocytes was compared to 6-carboxyfluorescein leakage from both ghosts and erythrocyte lipid vesicles, whereas leakage of enzymes from mitochondria and the apical and baso-lateral side of Caco-2 cells was determined. Furthermore, the effects of glycoalkaloids on the gap-junctional communication between Caco-2 cells was studied. From these experiments, it was found that glycoalkaloids specifically induced membrane disruptive effects of cholesterol containing membranes as was previously reported in model membrane studies. In addition, alpha-chaconine was found to selectively decrease gap-junctional intercellular communication. Furthermore, the glycoalkaloids were more potent in permeabilizing the outer membrane of mitochondria compared to digitonin at the low concentrations used. |
| Glycodelin-S in human seminal plasma reduces cholesterol efflux and inhibits capacitation of spermatozoa Chiu, P. C., M. K. Chung, et al. (2005), J Biol Chem 280(27): 25580-9. Abstract: Tight control of sperm capacitation is important for successful fertilization. Glycodelin-S is one of the most abundant glycoproteins in the human seminal plasma. However, its function is unclear. We investigated the role of glycodelin-S on capacitation of human spermatozoa. Binding kinetics experiments demonstrated the presence of two saturable and reversible binding sites of glycodelin-S on human spermatozoa. Differently glycosylated other isoforms of glycodelin, glycodelin-A and -F, did not compete with glycodelin-S for these binding sites, suggesting that the glycodelin-S binding sites are different from those of the other isoforms. Indirect immunofluorescent staining revealed specific binding of glycodelin-S around the sperm head. This immunoreactivity was greatly reduced in spermatozoa that had migrated through the cervical mucus surrogates. Glycodelin-S at physiological concentrations significantly reduced the bovine serum albumin and cyclodextrin-induced cholesterol efflux and down-regulated the adenylyl cyclase/protein kinase A/tyrosine kinase signaling pathway, resulting in suppression of capacitation. Deglycosylation abolished glycodelin-S binding and the effect of glycodelin-S on bovine serum albumin-induced capacitation. This indicates that the carbohydrate moiety of glycodelin-S is critical for the function of the molecule. It is concluded that glycodelin-S in seminal plasma maintains the uncapacitated state of human spermatozoa. |
| Glycophorin-induced cholesterol-phospholipid domains in dimyristoylphosphatidylcholine bilayer vesicles Tampe, R., A. von Lukas, et al. (1991), Biochemistry 30(20): 4909-16. Abstract: Glycophorin has been incorporated into unilamellar cholesterol-containing dimyristoylphosphatidylcholine vesicles that were reconstituted by the freeze and thaw technique. Evidence was obtained for a protein-induced structural reorganization of these mixed membranes. By differential scanning calorimetry, we were able to construct a phase diagram for the phospholipid/cholesterol mixture consisting of a liquid-ordered, a solid-ordered, and a liquid-disordered phase. Glycophorin at low molar fractions (XG less than 3 X 10(-3)) increases the relative amount of lipid in the liquid-ordered phase, which is interpreted as an enrichment of cholesterol in the vicinity of the protein. The formation of such steroid-enriched domains could be demonstrated directly by electron paramagnetic resonance using a spin-labeled cholesterol analogue. A drastic increase of the spin-spin interaction of the labeled steroid was observed in the presence of glycophorin. |
| Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1/apolipoprotein A-I pathway: 1-phenyl-2-decanoylamino-3-morpholino-1-propanol is a novel cholesterol efflux accelerator Glaros, E. N., W. S. Kim, et al. (2005), J Biol Chem 280(26): 24515-23. Abstract: Cellular glycosphingolipid (GSL) storage is known to promote cholesterol accumulation. Although physical interactions between GSLs and cholesterol are thought to cause intracellular cholesterol "trapping," it is not known whether cholesterol homeostatic mechanisms are also impaired under these conditions. ApoA-I-mediated cholesterol efflux via ABCA1 (ATP-binding cassette transporter A1) is a key regulator of cellular cholesterol balance. Here, we show that apoA-I-mediated cholesterol efflux was inhibited (by up to 53% over 8 h) when fibroblasts were treated with lactosylceramide or the glucocerebrosidase inhibitor conduritol B epoxide. Furthermore, apoA-I-mediated cholesterol efflux from fibroblasts derived from patients with genetic GSL storage diseases (Fabry disease, Sandhoff disease, and GM1 gangliosidosis) was impaired compared with control cells. Conversely, apoA-I-mediated cholesterol efflux from fibroblasts and cholesterol-loaded macrophage foam cells was dose-dependently stimulated (by up to 6-fold over 8 h) by the GSL synthesis inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). Unexpectedly, a structurally unrelated GSL synthesis inhibitor, N-butyldeoxynojirimycin, was unable to stimulate apoA-I-mediated cholesterol efflux despite achieving similar GSL depletion. PDMP was found to up-regulate ABCA1 mRNA and protein expression, thereby identifying a contributing mechanism for the observed acceleration of cholesterol efflux to apoA-I. This study reveals a novel defect in cellular cholesterol homeostasis induced by GSL storage and identifies PDMP as a new agent for enhancing cholesterol efflux via the ABCA1/apoA-I pathway. |
| Glycosphingolipid backbone conformation and behavior in cholesterol-containing phospholipid bilayers Hamilton, K. S., H. C. Jarrell, et al. (1993), Biochemistry 32(15): 4022-8. Abstract: 2H NMR spectroscopy was used to consider correspondence between existing single-crystal X-ray data for glycosphingolipids and their ceramide backbone conformation in fluid phospholipid membranes. A monoglycosylated sphingolipid, glucosylceramide (GlcCer), which represents the core structure of many important glycosphingolipids, was derived by partial synthesis through replacement of all native fatty acids with the 18-carbon species, stearic acid, deuterated at C2. N-2,2-2H2stearoyl-GlcCer was used to probe glycosphingolipid orientation and motion at low concentration in "fluid" phospholipid bilayers composed of dimyristoylphosphatidylcholine (DMPC), with and without physiological amounts of cholesterol. Spectral analysis, aided by stereoselective monodeuteration of the GlcCer fatty acid at C2, demonstrated that glycosphingolipid average acyl chain backbone conformation in fluid phospholipid membranes, with or without cholesterol, is likely closely related to that predicted from single crystal X-ray studies Pascher, I. (1976) Biochim. Biophys. Acta 455, 433-451; Pascher, I., & Sundell, S. (1977) Chem. Phys. Lipids 20, 175-191. To test the generality of this observation, specific comparisons were made involving galactosylceramide (GalCer) and globoside. GalCer provided a glycolipid differing only in monosaccharide stereochemistry (galactose vs glucose). Globoside permitted isolation of the effect of headgroup size, since it is derived from GlcCer via extension of the carbohydrate portion by the oligosaccharide, GalNAc beta 1-->3Gal alpha 1-->4Gal attached in beta 1-->4 linkage to the Glc residue.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Glycosphingolipid fatty acid arrangement in phospholipid bilayers: cholesterol effects Morrow, M. R., D. Singh, et al. (1995), Biophys J 68(1): 179-86. Abstract: Deuterium wide line NMR spectroscopy was used to study cholesterol effects on the ceramide portions of two glycosphingolipids (GSLs) distributed as minor components in fluid membranes. The common existence of very long fatty acids on GSLs was taken into account by including one glycolipid species with fatty acid chain length matching that of the host matrix, and one longer by 6 carbons. N-stearoyl and N-lignoceroyl galactosyl ceramide with perdeuterated fatty acid (18:0d35 GalCer and 24:0d47 GalCer) were prepared by partial synthesis. They were dispersed in bilayer membranes having the 18-carbon-fatty-acid phospholipid, 1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC), as major component. Glycolipid fatty acid chain behavior and arrangement were analyzed using order profiles derived from their 2H-NMR spectra. Cholesterol effects on order parameter profiles for 18:0d35 GalCer, with chain length equal to that of the host matrix, followed the pattern known for acyl chains of phospholipids. The presence of sterol led to restriction of trans/gauche isomerization along the length of the chain, with the largest absolute increase in order parameters being toward the surface, but somewhat greater relative effect just below the "plateau" region. In cholesterol-containing membranes, order parameter profiles for the long chain species, 24:0d47 GalCer, showed a characteristic secondary "plateau" associated with carbon atoms C14 to C23, a feature also present in SOPC bilayers without cholesterol and in pure hydrated 24:0d47 GalCer. Cholesterol-induced ordering effects on the long chain glycolipid were similar to those described for the shorter chain species, but were minimal at the methyl terminus.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Glycosphingolipid headgroup orientation in fluid phospholipid/cholesterol membranes: similarity for a range of glycolipid fatty acids Morrow, M. R., D. M. Singh, et al. (1995), Biophys J 69(3): 955-64. Abstract: Galactosyl ceramide (GalCer) was labeled for nuclear magnetic resonance (NMR) spectroscopy by replacement of a hydrogen atom at C6 of the galactose residue with deuterium. Wideline 2H NMR of d1GalCer permitted consideration of a mechanism traditionally entertained for cell surface recognition site modulation: that the nature of the fatty acid attached to the sphingosine backbone of glycosphingolipids (GSLs) importantly influences carbohydrate headgroup orientation. Comparison was made among various glycolipid fatty acids by altering hydroxylation, saturation, and chain length. Studies were carried out in unsonicated bilayer membranes mimicking several important characteristics of cell plasma membranes: fluidity, low GSL content, predominant sn-2monounsaturated phosphatidylcholine (PC) (1-palmitoyl-2-oleoyl PC), and the presence of cholesterol. Spectroscopy was performed on samples over a range of temperatures, which included the physiological. 2H NMR spectra of d1GalCer having 18-carbon saturated fatty acid (stearic acid), cis-9-unsaturated fatty acid (oleic acid), D- and L-stereoisomers of alpha-OH stearic acid, or 24-carbon saturated fatty acid (lignoceric acid) were importantly similar. This argues that for GSLs dispersed as minor components in fluid membranes, variation of the glycolipid fatty acid does not provide as much potential for direct conformational modulation of the carbohydrate portion as has sometimes been assumed. However, there was some evidence of motional differences among the species studied. The 2H NMR spectra that were obtained proved to be more complex than was anticipated. Their features could be approximated by assuming a combination of axially symmetric and axially asymmetric glycolipid motions. Presuming the appropriateness of such a analysis, at a magnetic field of 3.54 T (23.215 MHz), the experimental spectra suggested predominantly asymmetric motional contributions. At the higher field of 11.7 T (76.7 MHz, equivalent to a proton frequency of 500 MHz), spectra indicated dominance by axially symmetric rotational modes. There was also evidence of some bilayer orientation in the stronger magnetic field. The unusual observation of spectral differences between the two magnetic field strengths may involve a diamagnetic response to high field on the part of some liposome physical characteristics. |
| Glycosylation structure and enzyme activity of lecithin:cholesterol acyltransferase from human plasma, HepG2 cells, and baculoviral and Chinese hamster ovary cell expression systems Miller, K. R., J. Wang, et al. (1996), J Lipid Res 37(3): 551-61. Abstract: The glycosylation state of lecithin:cholesterol acyltransferase (LCAT) may be important in determining its enzymatic activity. We compared glycosylation structure, enzyme kinetics, and phosphatidylcholine (PC) acyl specificity of human LCAT from four sources: human plasma (pLCAT), media from HepG2 cells (HepG2 LCAT), media from SF21 cells infected with a recombinant baculovirus (bLCAT) and media from stably transfected Chinese hamster ovary (CHO) cells (CHO LCAT). bLCAT was underglycosylated (molecular weight approximately 50 kDa) and resistant to digestion by N-glycanase F, endoglycosidase F, and neuraminidase. CHO and HepG2 LCAT were overglycosylated (approximately 68 kDa and approximately 70-75 kDa) compared to pLCAT (approximately 65 kDa). CHO LCAT, like pLCAT, was sensitive to N-glycanase F and neuraminidase but not to endoglycosidase F. HepG2 LCAT demonstrated resistance to N-glycanase F and endoglycosidase F. Apparent Km values for all four enzymes were similar (1.4-9.2 microM cholesterol) for recombinant high density lipoproteins (rHDL) containing sn-1 16:0, sn-2 18:1 PC (POPC). Apparent Vmax values (nmol cholesteryl ester formed/h per micrograms) were 52.6 for pLCAT, 48.6 for CHO LCAT, 15.3 for bLCAT, and 8.3 for HepG2 LCAT. Changes in PC acyl specificity in the presence and absence of cholesterol were characterized by comparing the ratio of LCAT activity on rHDL containing sn-1 16:0, sn-2 20:4 PC (PAPC) or POPC (PAPC/POPC activity ratio). The ratios for pLCAT, bLCAT, CHO LCAT, and HepG2 LCAT activity were 0.63, 0.49, 0.56, and 0.51 with cholesterol and 0.34, 0.29, 0.36, and 0.99 without cholesterol, respectively. We conclude that LCAT source influences glycosylation structure, which affects the apparent Vmax for cholesteryl ester formation with only minor changes in apparent Km or acyl substrate specificity. |
| GM-CSF-mediated impairment of liver to synthesize albumin, cholinesterase, and cholesterol Takahashi, M., K. Nikkuni, et al. (1991), Am J Hematol 36(3): 213-4. Abstract: Serum albumin, cholinesterase, and cholesterol were measured in ten patients with aplastic anemia and eight with myelodysplastic syndrome who received the administration of recombinant human GM-CSF. Serum albumin, cholinesterase, and cholesterol were significantly lowered by the administration of GM-CSF and recovered after the cessation of GM-CSF. These data suggest that GM-CSF impairs the biosynthesis of liver cells and that cholesterol-lowering activity of GM-CSF, which is previously reported, is due to the impairment of liver biosynthesis by GM-CSF. |
| Goal attainment and maintenance of serum cholesterol level in a pharmacist-coordinated lipid clinic O'Donnell, D. C., N. T. Chen, et al. (2001), Am J Health Syst Pharm 58(4): 325-30. |