| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Human oxytocin receptors in cholesterol-rich vs. cholesterol-poor microdomains of the plasma membrane Gimpl, G. and F. Fahrenholz (2000), Eur J Biochem 267(9): 2483-97. Abstract: We analyzed the properties of a G protein-coupled receptor localized in cholesterol-poor vs. cholesterol-rich microdomains of the plasma membrane. For this purpose, the human oxytocin receptor, which is very sensitive against alterations of the membrane cholesterol level, was stably expressed in HEK293 cells. To calculate the total number of receptors independent of ligand binding studies, the oxytocin receptor was tagged with an enhanced green fluorescent protein (EGFP) which did not change the functional properties of the receptor. Only 1% of the oxytocin receptors were present in cholesterol-rich detergent-insoluble domains. In contrast, employing a detergent-free fractionation scheme that preserves the functional activity of the receptor, we detected 10-15% of the receptors in cholesterol-rich low-density membranes and therein the high-affinity state receptors were twofold enriched. In cholesterol-poor vs. cholesterol-rich domains, high-affinity oxytocin receptors behaved similar with respect to their agonist binding kinetics and GTP sensitivity. However, high-affinity oxytocin receptors localized in cholesterol-rich low-density membranes showed a markedly enhanced (t (1/2) approximately threefold) stability at 37 degrees C as compared with the oxytocin receptors localized in the cholesterol-poor high-density membranes. Addition of cholesterol to the high-density membranes fully protected the oxytocin receptors against loss of function. The importance of cholesterol to stabilize the oxytocin receptor was supported in experiments with solubilized receptors. Cholesterol markedly delayed the inactivation of oxytocin receptors solubilized with Chapso. In conclusion, the data of this report suggest that functional properties of heptahelical receptor proteins could differ in dependence of their localization in different membrane microdomains. |
| Human pedigree-based quantitative-trait-locus mapping: localization of two genes influencing HDL-cholesterol metabolism Almasy, L., J. E. Hixson, et al. (1999), Am J Hum Genet 64(6): 1686-93. Abstract: Common disorders with genetic susceptibilities involve the action of multiple genes interacting with each other and with environmental factors, making it difficult to localize the specific genetic loci responsible. An important route to the disentangling of this complex inheritance is through the study of normal physiological variation in quantitative risk factors that may underlie liability to disease. We present an analysis of HDL-cholesterol (HDL-C), which is inversely correlated with risk of heart disease. A variety of HDL subphenotypes were analyzed, including HDL particle-size classes and the concentrations and proportions of esterified and unesterified HDL-C. Results of a complete genomic screen in large, randomly ascertained pedigrees implicated two loci, one on chromosome 8 and the other on chromosome 15, that influence a component of HDL-C-namely, unesterified HDL2a-C. Multivariate analyses of multiple HDL phenotypes and simultaneous multilocus analysis of the quantitative-trait loci identified permit further characterization of the genetic effects on HDL-C. These analyses suggest that the action of the chromosome 8 locus is specific to unesterified cholesterol levels, whereas the chromosome 15 locus appears to influence both HDL-C concentration and distribution of cholesterol among HDL particle sizes. |
| Human placental cholesterol side-chain cleavage: enzymatic synthesis of (22R)-20 alpha,22-dihydroxycholesterol Tuckey, R. C. and K. J. Cameron (1993), Steroids 58(5): 230-3. Abstract: (22R)-20 alpha,22-Dihydroxycholesterol is the second intermediate in the conversion of cholesterol to pregnenolone by cytochrome P450scc in steroidogenic tissues. We report a rapid method for the enzymatic synthesis of (22R)-20 alpha,22-dihydroxycholesterol from (22R)-22-hydroxycholesterol using mitochondria from the human placenta. |
| Human plasma lecithin:cholesterol acyltransferase. On the substrate efficiency of cholest-5-ene-3 beta-thiol as a fatty acyl acceptor Zhou, G. and P. J. Dolphin (1995), Biochim Biophys Acta 1258(2): 101-6. Abstract: Lecithin:cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyses cholesteryl ester formation from lecithin and cholesterol present in the surface of plasma lipoproteins. Sterol fatty acid acceptors have previously been shown to require the presence of a trans conformation of the A/B ring and a 3 beta-OH group. Our laboratory has, however, demonstrated that two thiol sites within LCAT can become fatty acylated following lecithin cleavage although this does not appear to be essential for catalysis. In order to assess the ability of LCAT to donate a fatty acid derived from the sn-2 position of lecithin and present as an acyl enzyme intermediate (linked via an oxyester bond to Ser-181) to a sulfhydryl residue, we evaluated the ability of cholest-5-ene-3 beta-thiol to act as a substrate for cholesterol ester formation by LCAT. Thiocholesterol was a good terminal fatty acyl acceptor when incorporated into synthetic proteoliposomes containing lecithin/thiocholesterol/apo A-I in the molar ratios of 250:15:0.8. The Km for thiocholesterol was 203.6 microM with a Vmax of 5.3 nmol thiocholesteryl ester formed/h per microgram. The Km for cholesterol when substituted for thiocholesterol in the proteoliposomes was 29.5 microM with a Vmax of 8.8 nmol cholesteryl ester formed/h per microgram. Thiocholesterol and cholesterol were shown to occupy the same catalytic site in LCAT. Thus, thiocholesterol exhibits approx. 10% of the substrate efficiency of cholesterol when incubated with pure human LCAT. We conclude that LCAT can transacylate a fatty acyl moiety from the sn-2 position of lecithin to the 3 beta-SH group of thiocholesterol forming a cholesteryl thioester. Although the 3 beta-SH group is not as good a terminal acceptor as the 3 beta-OH group of cholesterol, LCAT is clearly capable of transacylating a fatty acid esterified via an oxyester linkage to one containing a thioester. |
| Human polymorphonuclear leukocyte phagocytosis of crystalline cholesterol, bilirubin, and calcium hydroxyapatite in vitro Prystowsky, J. B., J. S. Huprikar, et al. (1995), Dig Dis Sci 40(2): 412-8. Abstract: We tested the hypothesis that human polymorphonuclear leukocytes (PMNs) phagocytize crystalline cholesterol, bilirubin, or calcium hydroxyapatite in vitro and in the process release oxygen metabolites and enzymes involved in the inflammatory process. Chemiluminescence (CL), elicited by the respiratory burst (release and activation of oxygen metabolites and enzymes) of PMNs during phagocytosis of a target particle, was used to quantitate PMN phagocytosis of each crystal. Significant CL (P < 0.05) was observed with cholesterol concentrations of 1.3-5.3 mg/ml and the dose-response was linear (r > or = 0.95). With bilirubin, significant CL was observed with concentrations of 0.07-0.33 mg/ml. The response to calcium hydroxyapatite was variable. Human PMNs phagocytize cholesterol, bilirubin, and to a lesser extent, calcium hydroxyapatite. PMN chemiluminescence was associated with phagocytosis, indicating that inflammatory substances are being released in the process. These results support the concept that crystals that occur in the gallbladder may initiate gallbladder inflammation. |
| Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux Mulcahy, J. V., D. R. Riddell, et al. (2004), Biochem J 377(Pt 3): 741-7. Abstract: Although studies in recombinant cells indicate that scavenger receptor class B, type I (SR-BI) can promote cholesterol efflux, investigations in transgenic mice overexpressing or deficient in SR-BI endorse its physiological function as selectively sequestering cholesteryl esters from high-density lipoproteins (HDLs). Less clear is the role of SR-BII, a splice variant of the SR-B gene that differs only in the C-terminal cytoplasmic domain. Here, we identify several putative signalling motifs in the C-terminus of human SR-BII, which are absent from SR-BI, and hypothesize that these motifs interact with signalling molecules to mobilize stored cholesteryl esters and/or promote the efflux of intracellular free cholesterol. 'Pull-down' assays using a panel of tagged SH3 (Src homology 3) domains showed that cytoplasmic SR-BII, but not cytoplasmic SR-BI, bound the SH3 domain of phospholipase C-gamma1; this interaction was not, however, detected under more physiological conditions. Specific anti-peptide antisera identified SR-BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed receptor localization to caveolae, a plasma membrane microdomain that concentrates signal-transducer molecules and acts as a conduit for cholesterol flux between cells and lipoproteins. Consistent with its caveolar localization, expression of human SR-BII in recombinant Chinese hamster ovary cells (CHO-SR-BII) was associated with increased HDL-mediated cholesterol efflux. Nevertheless, when CHO-SR-BII cells were pre-loaded with cholesteryl (3)Holeate and incubated with HDL, cholesteryl ester stores were not reduced compared with control cells. We conclude that although human SR-BII is expressed by macrophages, contains cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl esters. |
| Human secretory phospholipase A2 mediates decreased plasma levels of HDL cholesterol and apoA-I in response to inflammation in human apoA-I transgenic mice Tietge, U. J., C. Maugeais, et al. (2002), Arterioscler Thromb Vasc Biol 22(7): 1213-8. Abstract: OBJECTIVE: Plasma levels of high density lipoprotein (HDL) cholesterol and apolipoprotein (apo)A-I are decreased in inflammatory states. Secretory phospholipase A2 (sPLA2), an acute-phase protein, may play a key role in the pathophysiology of this phenomenon. METHODS AND RESULTS: To investigate the effects of sPLA2 on human-like HDL particles in vivo, we generated transgenic mice overexpressing human apoA-I and human sPLA2 (apoA-I/sPLA2 mice). Compared with apoA-I mice, apoA-I/sPLA2 mice had significantly lower plasma levels of phospholipids, HDL cholesterol, and apoA-I (each P<0.01). HDL from apoA-I/sPLA2 mice was significantly depleted in phospholipids and cholesteryl esters (each P<0.001) but was enriched in protein and triglycerides (each P<0.001). As assessed by gel filtration and nondenaturing gel electrophoresis, sPLA2 overexpression in apoA-I mice resulted in a dramatic shift of the HDL particle size toward smaller particles. Furthermore, virtually all plasma sPLA2 in apoA-I/sPLA2 mice was found in association with the HDL fraction. The acute-phase response was induced in apoA-I/sPLA2 double-transgenic and apoA-I single-transgenic mice by intraperitoneal lipopolysaccharide (LPS) injection. Plasma sPLA2 was significantly increased after LPS injection in apoA-I/sPLA2 mice. Twelve hours after LPS administration, plasma total cholesterol, HDL cholesterol, apoA-I, and phospholipids were unchanged in apoA-I transgenic control mice but had decreased significantly in the apoA-I/sPLA2 mice (-57%, -62%, and -54%, -61%, respectively; each P<0.001). Both groups of mice had increased plasma levels of serum amyloid A (SAA) in response to LPS. To test the hypothesis that SAA may be an in vivo activator of sPLA2, we specifically overexpressed SAA in apoA-I/sPLA2 mice by means of liver-directed gene transfer. Despite high plasma levels of SAA, plasma lipid and lipoprotein profiles were not different than those in control mice. CONCLUSIONS: These results in a mouse model of human-like HDL indicate that sPLA2 expression significantly influences HDL particle size and composition and demonstrate that an induction of sPLA2 is required for the decrease in plasma HDL cholesterol in response to inflammatory stimuli in mice and that this effect is independent of SAA. |
| Human seminal plasma prevents sperm from becoming acrosomally responsive to the agonist, progesterone: cholesterol is the major inhibitor Cross, N. L. (1996), Biol Reprod 54(1): 138-45. Abstract: Seminal plasma inhibits human sperm from developing the ability to undergo the acrosome reaction. The inhibitory activity was identified as that of cholesterol on the basis of its solubility in organic solvents, its chromatographic behavior (adsorption, thin-layer, and gas chromatography), and its mass spectrum. Contrary to findings in other reports, no evidence for inhibitory proteins or peptides was found, and spermine was not an effective inhibitor. The inhibitory activity of untreated seminal plasma from individual ejaculates was highly correlated with the cholesterol content of the ejaculates (r = 0.96), suggesting that the amount of cholesterol determines the inhibitory activity of unfractionated seminal plasma. The inhibitory activity of unfractionated seminal plasma was significantly less, relative to the cholesterol content, than the activity of pure cholesterol, which is consistent with the idea that there are components in seminal plasma that partially counter the effect of cholesterol by promoting the development of acrosomal responsiveness. |
| Human serum albumin and its structural variants mediate cholesterol efflux from cultured endothelial cells Ha, J. S., C. E. Ha, et al. (2003), Biochim Biophys Acta 1640(2-3): 119-28. Abstract: In the present study, we used the human EA.hy926 endothelial cell line as the model system to investigate the effect of human serum albumin (HSA) and its structural variants on cholesterol efflux. Initial studies showed that HSA promoted cholesterol efflux in a dose- and time-dependent manner, reaching a plateau at 10 mg/ml at 90 min. As a control, gelatin displayed no significant effect on efflux, while HSA was significantly more efficient than ovalbumin and bovine serum albumin (BSA) in promoting cholesterol efflux. Equal molar concentrations of HSA and apolipoprotein A-I (apoA-I) showed that apoA-I had considerably higher efficiency in efflux. However, the prevailing high plasma concentrations of HSA may compensate for its lower efflux rate compared to apoA-I. To characterize the mechanism of HSA-mediated cholesterol efflux, we studied the effects of cAMP and temperature on efflux using both EA.hy926 endothelial cells and murine RAW 264.7 macrophages. We found that HSA-mediated efflux occurred via a cAMP-independent and relatively temperature-insensitive pathway. We next examined the nature of HSA-cholesterol interaction by comparing the effects of various HSA mutants to wild-type HSA on cholesterol efflux. We found specific interactions between subdomains 2A and 3A and cholesterol, as indicated by the changes in the efflux rate of various HSA mutants. In conclusion, our study provides evidence for the role of HSA in cholesterol efflux, and shows that the substitution of specific amino acid residues in subdomains of 2A and 3A may be important structural determinants in its ability to bind to cholesterol and participate in cholesterol efflux. |
| Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: possible role for its phospholipase-A2-like activity and lysophosphatidylcholine formation Rozenberg, O., D. M. Shih, et al. (2003), Arterioscler Thromb Vasc Biol 23(3): 461-7. Abstract: OBJECTIVE: Human serum paraoxonase 1 (PON1) activity is inversely related to the risk of developing an atherosclerotic lesion, which contains cholesterol-loaded macrophage foam cells. To assess a possible mechanism for this relationship, we analyzed the effect of PON1 on cellular cholesterol biosynthesis. METHODS AND RESULTS: Mouse peritoneal macrophages (MPMs) were harvested from PON1-deficient mice (PON1o and PON1o/Eo mice on the genetic background of C57BL/6J and Eo mice, respectively). PON1o/Eo mice exhibited a significantly 51% increased atherosclerotic lesion area and 35% increased macrophage cholesterol content compared with control E degrees mice. In parallel, macrophage cholesterol biosynthesis rates were increased in PON1-deficient mice MPMs by 50% compared with their controls. Incubation of macrophages with human PON1 revealed a dose-dependent inhibitory effect (up to 84%) on macrophage cholesterol biosynthesis. We demonstrated a PON1 phospholipase-A2-like activity on MPMs, evidenced by release of polyunsaturated fatty acids and formation of lysophosphatidylcholine. On incubation of macrophages with lysophosphatidylcholine, a dose-dependent inhibition (up to 40%) of cellular cholesterol biosynthesis was noted. The inhibitory effect of PON1 on macrophage cholesterol biosynthesis was shown to be downstream to mevalonate, probably at the lanosterol metabolic point. CONCLUSIONS: PON1 inhibits macrophage cholesterol biosynthesis and atherogenesis probably through its phospholipase-A2-like activity. |
| Human sterol 27-hydroxylase (CYP27) overexpressor transgenic mouse model. Evidence against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis Meir, K., D. Kitsberg, et al. (2002), J Biol Chem 277(37): 34036-41. Abstract: CYP27-overexpressed transgenic mice were generated with the use of a human full-length CYP27 coding region cloned into a ubiquitous expression vector. Positive transgenic mice were identified by tail DNA genotyping and high fecal 27-hydroxycholesterol content. The levels of 27-hydroxycholesterol were found to be 3-5 times higher in the circulation and the tissues of the overexpressed mice when compared with littermate controls. There were no gross morphological differences between the overexpressed mice and their controls. Total cholesterol and triglyceride levels were not affected by overexpression of CYP27. Serum lathosterol was also normal, suggesting a normal rate of cholesterol synthesis. Serum levels of 7alpha-hydroxycholesterol were unaffected, suggesting a normal rate of bile acid formation in the pathway involving cholesterol 7alpha-hydroxylase. Biliary bile acid composition was slightly affected by CYP27 overexpression in female but not in male mice. Fecal levels of neutral steroids were slightly but significantly increased in overexpressor female mice but not in male mice. Levels of 24-hydroxycholesterol in the circulation were significantly reduced in the overexpressed mice, probably as a consequence of a recently described catabolic pathway involving CYP27. Combined with the results of our previous work on mice with a disruption of the CYP27 gene, the present results suggest that the levels of 27-hydroxycholesterol are not of critical importance for cholesterol homeostasis in mice. |
| Hyaluronan (HYAL-BV 5200) inhibits neo-intimal macrophage influx after balloon-catheter induced injury in the cholesterol-fed rabbit Ferns, G. A., M. Konneh, et al. (1995), Atherosclerosis 114(2): 157-64. Abstract: Hyaluronan is a glycosaminoglycan, elaborated by several cell types, and is a major constituent of the extracellular matrix. Recent studies suggest that hyaluronan influences cell migration and proliferation. At high concentrations, it has been shown to inhibit macrophage migration in vitro. We have investigated the effects of hyaluronan administration on neo-intimal lesion development following balloon catheter injury of the common carotid artery in the cholesterol-fed New Zealand White rabbit. Hyaluronan, administered as sodium hyaluronate at the time of surgery and daily until sacrifice, 2 weeks later, reduced the absolute neo-intimal response to injury by 42% (117 +/- 16 microns to 68 +/- 11 microns; P < 0.05), and the intima-media ratio by 35% (0.91 +/- 0.10 to 0.59 +/- 0.11; P < 0.05). This was associated with a 62% reduction in intimal macrophage content (8.63 +/- 1.85% to 3.25 +/- 1.05%; P < 0.02). At the time of killing, serum cholesterol levels and weight gain were comparable between the groups of animals receiving a cholesterol diet (P > 0.05). In both groups mean serum cholesterol levels at the time of the balloon injury and killing were significantly greater than at entry (P < 0.001), and significantly higher than in a group receiving control chow (P < 0.001). These data suggest that the effect of hyaluronic acid on neo-intimal size may be mediated, in part, by an inhibition of monocyte/macrophage influx, and support the view that hyaluronan impairs monocyte migration. |
| Hydration of phospholipid bilayers in the presence and absence of cholesterol Bach, D. and I. R. Miller (2005), Chem Phys Lipids 136(1): 67-72. Abstract: The number of water molecules bound (unfreezable) by a molecule of dipalmitoyl phosphatidylserine (DPPS) or by a molecule of dipalmitoyl phosphatidylcholine (DPPC) alone or in mixtures with cholesterol was determined by differential scanning calorimetry (DSC). When the phospholipids are in the gel state and in the absence of cholesterol, molecule of DPPS binds about 3.5 molecules of water and molecule of DPPC binds about 6 molecules of water. Number of water molecules bound increases when cholesterol crystallites are formed in the bilayer. For DPPS-cholesterol mixture at X(chol) -0.5, as well as for DPPC-cholesterol mixture at X(chol) -0.5 about 7 water molecules are bound. |
| Hydrocele and cholesterol granuloma of the tunica vaginalis simulating a tumor in echography Farina Perez, L. A., P. Menendez, et al. (1998), Actas Urol Esp 22(1): 70-3. Abstract: OBJECTIVE: A case of cholesterol granuloma of tunica vaginalis, with an equivocal ultrasound image but typical histopathological picture, is described. PATIENT AND METHOD: A 33-year-old man complained of a painless scrotal mass of 17 years duration. The mass was 10 cm in diameter, could not be transilluminated and appeared as paratesticular and solid on ultrasound, suggesting a tumor. At operation an old hydrocele with cholesterol crystals and cholesterol granuloma of tunica vaginalis was found. A partial resection of tunica vaginalis was performed, sparing the testis. COMMENT: Cholesterol granuloma is a rare inflammatory reaction of tunica vaginalis, that may simulate an intrascrotal tumor on physical examination, on ultrasound and at operation. |
| Hydrogel network entrapping cholesterol oxidase and octadecylsilica for optical biosensing in hydrophobic organic or aqueous micelle solvents Wu, X. J. and M. M. Choi (2003), Anal Chem 75(16): 4019-27. Abstract: Two optical cholesterol biosensors have been fabricated by immobilizing cholesterol oxidase (ChOx) and octadecylsilica (ODS) particles in hydrogel network matrixes of copolymer of poly(vinyl alcohol) (PVA)/hydroxyethyl carboxymethyl cellulose (HECMC), and sol-gel, respectively. In conjunction with an optical oxygen transducer, the immobilized ChOx in the sol-gel/ODS matrix was assembled as an optical cholesterol biosensor to continuously detect free cholesterol in aqueous micelle solution, while the immobilized ChOx in the PVA/HECMC/ODS matrix was constructed as an organic-phase optical cholesterol biosensor for the continuous analysis of free cholesterol in hydrophobic organic solvent. The compositions and properties of the immobilization matrixes, the effects of solvents and the analytical features were studied in detail. Both biosensors showed stable and reliable responses toward free cholesterol. For the aqueous micelle cholesterol biosensor, the analytical working range was from 0.05 to 8.0 mM cholesterol, the response time was 7-12 min, the operation life was more than 35 assays, and the shelf life was approximately 4 months. For the organic-phase cholesterol biosensor, the analytical working range was from 0.07 to 18.0 mM cholesterol, the response time was 4-8 min, the operation life was more than 120 assays, and the shelf life was longer than 5 months. The organic-phase cholesterol biosensor has been successfully applied to determine the free cholesterol content in commercial butter samples. |
| Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women Matthan, N. R., K. Cianflone, et al. (2001), J Lipid Res 42(11): 1841-8. Abstract: To determine whether hydrogenated fat consumption alters triglyceride metabolism and cholesterol esterification rates, 14 women (65-71 years of age) were provided with each of four diets for 5-week periods according to a randomized cross-over design. The experimental diets contained either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines. Triglyceride uptake by adipose tissue was determined by measuring plasma acylation-stimulating protein (ASP), FFA, glucose, and insulin levels, while rates of transfer and esterification rate of newly synthesized cholesterol (ER) were derived by using plasma CETP levels and the deuterium incorporation methodology. Plasma ASP levels were lowest (P < 0.05) in subjects on the SM diet (33.4 +/- 12.7 nM) compared with the SO (48.7 +/- 17.0 nM) and SQM (50.7 +/- 15.7 nM) diets. Conversely, FFA were highest (P < 0.05) on the SM diet (0.86 +/- 0.45 mM) relative to all the other diets. No differences were observed in plasma glucose and insulin levels among diets. A trend toward higher CETP levels after consumption of the SM diet was observed. However, the ER was lowest (P < 0.05) after the SM (0.111 +/- 0.062 g x day(-1)) diet and highest after consumption of the SQM (0.216 +/- 0.123 g x day(-1)) diet. In addition, ASP levels were negatively correlated with FFA (r = -0.63, P < 0.05), LDL cholesterol (r = -0.56, P < 0.05), and TG (r = -0.41, P < 0.05), whereas FFA was positively correlated with apolipoprotein B-containing lipoproteins (r = 0.58 and 0.47, for VLDL and LDL cholesterol, P < 0.05), and negatively correlated with HDL cholesterol (r = -0.51, P < 0.05). The ER was found to positively correlate with HDL cholesterol and HDL2 subfraction (r = 0.53 and 0.45, respectively, P < 0.05). Taken together, these data demonstrate that the alterations in circulating lipid levels, commonly observed with consumption of hydrogenated fat-rich diets, can be explained in part by changes in ASP activity as well as newly synthesized cholesterol ER. |
| Hydrogenated fat consumption affects cholesterol synthesis in moderately hypercholesterolemic women Matthan, N. R., L. M. Ausman, et al. (2000), J Lipid Res 41(5): 834-9. Abstract: To determine mechanisms by which hydrogenated fat influences plasma lipid levels, 14 women (65;-71 yrs with LDL-C >/= 130 mg. dl(-)(1)) consumed, for 5-week periods each, a baseline (BL) diet (39% kcal fat, 164 mg chol. 1000 kcal(-)(1)) and reduced fat diets (30% kcal) where two-thirds of the fat was either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines, or butter (BT). Plasma lipid levels were analyzed at the end of each phase. Fractional synthesis rates (FSR) in pools/day (p. d(-)(1)) and absolute synthesis rates (ASR) in grams/day (g. d(-)(1)) of free cholesterol (FC) were measured using the deuterium incorporation methodology. Plasma total (P < 0.01) and low density lipoprotein (P < 0.05) cholesterol levels increased with increasing degree of hydrogenation or saturated fat intake. High density lipoprotein cholesterol levels (P < 0.05) were lowest on the SM diet when compared to the BT diet. Low trans SQM (0.081 +/- 0.019 p. d(-)(1)) and medium trans TM (0.086 +/- 0.029 p. d(-)(1)) diets elicited responses similar to the SO (0.078 +/- 0.024 p. d(-)(1)) diet, whereas high trans SM (0.053 +/- 0.029 p. d(-)(1)) diet mimicked the BT (0.062 +/- 0.017 p. d(-)(1)) and high fat BL (0.053 +/- 0.023 p. d(-)(1)) diet in its suppression (P < 0.05) of FSR-FC. ASR-FC, which is an approximation of the daily production of newly synthesized cholesterol, showed a trend similar to the FSR-FC data. These results indicate that reduced synthesis is not responsible for the higher plasma TC levels seen with consumption of the SM, BT, and BL diets, and suggest that another mechanism, possibly impairment of the catabolic pathway of cholesterol, is involved. |
| Hydrogenated fats and serum cholesterol levels Klurfeld, D. M. (1999), N Engl J Med 341(18): 1396; author reply 1396-7. |
| Hydrolethalus syndrome, in contrast to Smith-Lemli-Opitz syndrome, is not due to a defect in post-squalene cholesterol biosynthesis: a case report Rakheja, D., M. L. Cimo, et al. (2004), Am J Med Genet A 129(2): 212-3. |
| Hydrolysis of partially saturated egg phosphatidylcholine in aqueous liposome dispersions and the effect of cholesterol incorporation on hydrolysis kinetics Grit, M., N. J. Zuidam, et al. (1993), J Pharm Pharmacol 45(6): 490-5. Abstract: Hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine (PHEPC) were studied as a function of pH, temperature, buffer concentration, ionic strength, and the effect of cholesterol incorporation. Results showed that PHEPC has a maximum stability at around pH 6.5. General acid base catalysis was observed for acetate, HEPES and Tris buffers. Increasing the ionic strength of the buffer solutions did not influence the hydrolysis kinetics. The relationship between the observed hydrolysis rate constants and the temperature could adequately be described by the Arrhenius equation. Incorporation of cholesterol did not affect the hydrolysis kinetics. This result indicates that the hydrolysis kinetics of PHEPC do not depend on the changes in bilayer rigidity induced by cholesterol incorporation. Cholesterol is stable under the experimental conditions used in this study; no changes were observed in cholesterol concentration over the experimental time interval. |