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1
Jing, Xiangfeng, and Spencer T. Behmer. "Insect Sterol Nutrition: Physiological Mechanisms, Ecology, and Applications." Annual Review of Entomology 65, no. 1 (January 7, 2020): 251–71. http://dx.doi.org/10.1146/annurev-ento-011019-025017.
Анотація:
Insects, like all eukaryotes, require sterols for structural and metabolic purposes. However, insects, like all arthropods, cannot make sterols. Cholesterol is the dominant tissue sterol for most insects; insect herbivores produce cholesterol by metabolizing phytosterols, but not always with high efficiency. Many insects grow on a mixed-sterol diet, but this ability varies depending on the types and ratio of dietary sterols. Dietary sterol uptake, transport, and metabolism are regulated by several proteins and processes that are relatively conserved across eukaryotes. Sterol requirements also impact insect ecology and behavior. There is potential to exploit insect sterol requirements to ( a) control insect pests in agricultural systems and ( b) better understand sterol biology, including in humans. We suggest that future studies focus on the genetic mechanism of sterol metabolism and reverse transportation, characterizing sterol distribution and function at the cellular level, the role of bacterial symbionts in sterol metabolism, and interrupting sterol trafficking for pest control.
2
Zhou, Wenxu, Paxtyn M. Fisher, Boden H. Vanderloop, Yun Shen, Huazhong Shi, Adrian J. Maldonado, David J. Leaver та W. David Nes. "A nematode sterol C4α-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity". Journal of Lipid Research 61, № 2 (23 вересня 2019): 192–204. http://dx.doi.org/10.1194/jlr.ra119000317.
Анотація:
Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and Δ7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.
3
Vidkjær, Nanna H., Karl-Martin V. Jensen, René Gislum, and Inge S. Fomsgaard. "Profiling and Metabolism of Sterols in the Weaver Ant Genus Oecophylla." Natural Product Communications 11, no. 1 (January 2016): 1934578X1601100. http://dx.doi.org/10.1177/1934578x1601100114.
Анотація:
Sterols are essential to insects because they are vital for many biochemical processes, nevertheless insects cannot synthesize sterols but have to acquire them through their diet. Studies of sterols in ants are sparse and here the sterols of the weaver ant genus Oecophylla are identified for the first time. The sterol profile and the dietary sterols provided to a laboratory Oecophylla longinoda colony were analyzed. Most sterols originated from the diet, except one, which was probably formed via dealkylation in the ants and two sterols of fungal origin, which likely originate from hitherto unidentified endosymbionts responsible for supplying these two compounds. The sterol profile of a wild Oecophylla smaragdina colony was also investigated. Remarkable qualitative similarities were established between the two species despite the differences in diet, species, and origin. This may reflect a common sterol need/aversion in the weaver ants. Additionally, each individual caste of both species displayed unique sterol profiles.
4
Gallagher, Patricia A., Steven A. Warner, and Aristotle J. Domnas. "Presqualene metabolism in two species of Lagenidium." Canadian Journal of Microbiology 40, no. 10 (October 1, 1994): 858–64. http://dx.doi.org/10.1139/m94-136.
Анотація:
The fate of precursors of the isoprenoid pathway was studied in the sterol auxotroph Lagenidium giganteum and in the positive control organism Lagenidium callinectes. Acetate derived from glucose and mevalonic acid was converted to sterols and fatty acids in L. callinectes. Lagenidium giganteum converted mevalonic acid to sterols and fatty acids, but glucose-derived acetate was not utilized for sterol synthesis. The results showed that the defect in the isoprenoid pathway of L. giganteum occurs at the level of the β-hydroxy-β-methylglutarylcoenzyme A reductase–synthase complex. Various aspects of this defect are discussed relative to metabolism of the organism.Key words: Lagenidium giganteum, Lagenidium callinectes, glucose, mevalonic acid utilization, fatty acids, sterol production.
5
Benveniste, Pierre. "Sterol Metabolism." Arabidopsis Book 1 (January 2002): e0004. http://dx.doi.org/10.1199/tab.0004.
6
Tansley, Gavin, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, and Cheryl L. Wellington. "Sterol Lipid Metabolism in Down Syndrome Revisited: Down Syndrome Is Associated with a Selective Reduction in Serum Brassicasterol Levels." Current Gerontology and Geriatrics Research 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/179318.
Анотація:
Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer’s Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population’s unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with DS compared to age-matched controls. Here we report that the levels of nearly all lipids and lipoproteins examined are similar to control subjects, suggesting that trisomy 21 does not lead to pronounced general alterations in sterol lipid metabolism. However, the levels of serum brassicasterol were markedly reduced in DS subjects.
7
Whitaker, Bruce D. "LIPIDS IN SUBEPIDERMAL CORTICAL TISSUE OF `GOLDEN DELICIOUS' APPLE FRUIT." HortScience 30, no. 2 (April 1995): 191b—191. http://dx.doi.org/10.21273/hortsci.30.2.191b.
Анотація:
Altered metabolism of membrane lipids has been proposed as a mechanism for the beneficial effects of postharvest calcium treatment on apple quality. A previous study showed that after transfer of apples stored 6 months at 0C to 20C, calcium-treated fruit exhibited slower loss of galactolipid and altered levels of sterol conjugates. The present study of lipids in “control” fruit was conducted as a prelude to further in-depth analyses of the effects of postharvest calcium and heat treatments on lipid metabolism in apples during and after cold storage. Neutral lipid, glycolipid (GL), and phospholipid (PL) fractions were obtained by column chromatography followed by TLC separation of GL and PL classes. The major GL were steryl glycosides (SG), acylated steryl glycosides (ASG), cerebrosides (CB), and mono- and digalactosyl diacylglycerols. Phosphatidylcholine (PC) > P-ethanolamine (PE) > P-irositol (PI) were the major PL. The fatty acids of PC and PE were quite similar, whereas those of PI were more saturated. CB included only 2-hydroxy fatty acids. Among the steryl lipids, free sterols > SG > ASG, with beta-sitosterol >90% of the total sterol in each.
8
Najle, Sebastián R., María Celeste Molina, Iñaki Ruiz-Trillo, and Antonio D. Uttaro. "Sterol metabolism in the filasterean Capsaspora owczarzaki has features that resemble both fungi and animals." Open Biology 6, no. 7 (July 2016): 160029. http://dx.doi.org/10.1098/rsob.160029.
Анотація:
Sterols are essential for several physiological processes in most eukaryotes. Sterols regulate membrane homeostasis and participate in different signalling pathways not only as precursors of steroid hormones and vitamins, but also through its role in the formation of lipid rafts. Two major types of sterols, cholesterol and ergosterol, have been described so far in the opisthokonts, the clade that comprise animals, fungi and their unicellular relatives. Cholesterol predominates in derived bilaterians, whereas ergosterol is what generally defines fungi. We here characterize, by a combination of bioinformatic and biochemical analyses, the sterol metabolism in the filasterean Capsaspora owczarzaki , a close unicellular relative of animals that is becoming a model organism. We found that C. owczarzaki sterol metabolism combines enzymatic activities that are usually considered either characteristic of fungi or exclusive to metazoans. Moreover, we observe a differential transcriptional regulation of this metabolism across its life cycle. Thus, C. owczarzaki alternates between synthesizing 7-dehydrocholesterol de novo, which happens at the cystic stage, and the partial conversion—via a novel pathway—of incorporated cholesterol into ergosterol, the characteristic fungal sterol, in the filopodial and aggregative stages.
9
Gylling, Helena, and Tatu A. Miettinen. "The effect of plant stanol- and sterol-enriched foods on lipid metabolism, serum lipids and coronary heart disease." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 42, no. 4 (July 1, 2005): 254–63. http://dx.doi.org/10.1258/0004563054255605.
Анотація:
Phytosterols are plant sterols, mainly campesterol and sitosterol, and their respective stanols (5α-saturated derivatives), which chemically resemble cholesterol. They are present in a normal diet and are absorbed proportionally to cholesterol, but to a much lesser extent, such that less than 0.1% of serum sterols are plant sterols. Phytosterols inhibit intestinal cholesterol absorption, and fat-soluble plant stanol esters were introduced as a functional food for lowering serum cholesterol in the early 1990s; plant sterol esters entered the market at the end of the 1990s. Inhibition of the intestinal absorption of cholesterol stimulates cholesterol synthesis, a factor which limits serum cholesterol lowering to about 10% with phytosterols. Enrichment of the diet with plant stanol esters reduces absorption and serum concentrations of both cholesterol and plant sterols, whereas enrichment of the diet with plant sterol esters, especially in combination with statins, lowers serum cholesterol but increases serum plant sterol levels. Recent studies have suggested that high-serum plant sterol levels may be associated with increased coincidence of coronary heart disease. Estimates of coronary heart disease reduction by 20-25% with plant sterols/stanols is based mainly on short-term studies. Long-term cholesterol lowering, needed for the prevention of coronary heart disease, may be successful with plant stanol esters, which lower serum cholesterol in both genders over at least a year.
10
Jaramillo-Madrid, Ana Cristina, Justin Ashworth, and Peter J. Ralph. "Levels of Diatom Minor Sterols Respond to Changes in Temperature and Salinity." Journal of Marine Science and Engineering 8, no. 2 (February 1, 2020): 85. http://dx.doi.org/10.3390/jmse8020085.
Анотація:
Diatoms are a broadly distributed and evolutionarily diversified group of microalgae that produce a diverse range of sterol compounds. Sterols are triterpenoids that play essential roles in membrane-related processes in eukaryotic cells. Some sterol compounds possess bioactivities that promote human health and are currently used as nutraceuticals. The relationship between sterol diversity in diatoms and their acclimation to different environments is not well understood. In this study, we investigated the occurrence of different sterol types across twelve diatom species, as well as the effect of temperature reduction and changes in salinity on the sterol contents of three model diatom species. In the diatoms Thalassiosira pseudonana, Phaeodactylum tricornutum and Chaetoceros muelleri, we found that changes in the relative contents of minor sterols accompanied shifts in temperature and salinity. This may be indicative of acquired adaptive traits in diatom metabolism.
11
Guan, Xue Li, Cleiton M. Souza, Harald Pichler, Gisèle Dewhurst, Olivier Schaad, Kentaro Kajiwara, Hirotomo Wakabayashi, et al. "Functional Interactions between Sphingolipids and Sterols in Biological Membranes Regulating Cell Physiology." Molecular Biology of the Cell 20, no. 7 (April 2009): 2083–95. http://dx.doi.org/10.1091/mbc.e08-11-1126.
Анотація:
Sterols and sphingolipids are limited to eukaryotic cells, and their interaction has been proposed to favor formation of lipid microdomains. Although there is abundant biophysical evidence demonstrating their interaction in simple systems, convincing evidence is lacking to show that they function together in cells. Using lipid analysis by mass spectrometry and a genetic approach on mutants in sterol metabolism, we show that cells adjust their membrane composition in response to mutant sterol structures preferentially by changing their sphingolipid composition. Systematic combination of mutations in sterol biosynthesis with mutants in sphingolipid hydroxylation and head group turnover give a large number of synthetic and suppression phenotypes. Our unbiased approach provides compelling evidence that sterols and sphingolipids function together in cells. We were not able to correlate any cellular phenotype we measured with plasma membrane fluidity as measured using fluorescence anisotropy. This questions whether the increase in liquid order phases that can be induced by sterol–sphingolipid interactions plays an important role in cells. Our data revealing that cells have a mechanism to sense the quality of their membrane sterol composition has led us to suggest that proteins might recognize sterol–sphingolipid complexes and to hypothesize the coevolution of sterols and sphingolipids.
12
Yutuc, Eylan, Roberto Angelini, Mark Baumert, Natalia Mast, Irina Pikuleva, Jillian Newton, Malcolm R. Clench, et al. "Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism." Proceedings of the National Academy of Sciences 117, no. 11 (March 4, 2020): 5749–60. http://dx.doi.org/10.1073/pnas.1917421117.
Анотація:
Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatization in combination with microliquid extraction for surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400-µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-to-ionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type andcholesterol 24S-hydroxylaseknockout mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.
13
Scolaro, Bianca, Leticia F. S. de Andrade, and Inar A. Castro. "Cardiovascular Disease Prevention: The Earlier the Better? A Review of Plant Sterol Metabolism and Implications of Childhood Supplementation." International Journal of Molecular Sciences 21, no. 1 (December 24, 2019): 128. http://dx.doi.org/10.3390/ijms21010128.
Анотація:
Atherosclerosis is the underlying cause of major cardiovascular events. The development of atherosclerotic plaques begins early in life, indicating that dietary interventions in childhood might be more effective at preventing cardiovascular disease (CVD) than treating established CVD in adulthood. Although plant sterols are considered safe and consistently effective in lowering plasma cholesterol, the health effects of early-life supplementation are unclear. Studies suggest there is an age-dependent effect on plant sterol metabolism: at a younger age, plant sterol absorption might be increased, while esterification and elimination might be decreased. Worryingly, the introduction of low-cholesterol diets in childhood may unintentionally favor a higher intake of plant sterols. Although CVD prevention should start as early as possible, more studies are needed to better elucidate the long-term effects of plant sterol accumulation and its implication on child development.
14
Fujii, Thais Tenorio Soares, Pollyanna Stephanie Gomes, Rubens Lima do Monte-Neto, Daniel Claudio de Oliveira Gomes, Marc Ouellette, Eduardo Caio Torres-Santos, Valter Viana Andrade-Neto, and Herbert Leonel de Matos Guedes. "Simvastatin Resistance of Leishmania amazonensis Induces Sterol Remodeling and Cross-Resistance to Sterol Pathway and Serine Protease Inhibitors." Microorganisms 10, no. 2 (February 9, 2022): 398. http://dx.doi.org/10.3390/microorganisms10020398.
Анотація:
The sterol biosynthesis pathway of Leishmania spp. is used as a pharmacological target; however, available information about the mechanisms of the regulation and remodeling of sterol-related genes is scarce. The present study investigated compensatory mechanisms of the sterol biosynthesis pathway using an inhibitor of HMG-CoA reductase (simvastatin) and by developing drug-resistant parasites to evaluate the impact on sterol remodeling, cross-resistance, and gene expression. Simvastatin-resistant L. amazonensis parasites (LaSimR) underwent reprogramming of sterol metabolism manifested as an increase in cholestane- and stigmastane-based sterols and a decrease in ergostane-based sterols. The levels of the transcripts of sterol 24-C-methyltransferase (SMT), sterol C14-α-demethylase (C14DM), and protease subtilisin (SUB) were increased in LaSimR. LaSimR was cross-resistance to ketoconazole (a C14DM inhibitor) and remained sensitive to terbinafine (an inhibitor of squalene monooxygenase). Sensitivity of the LaSimR mutant to other antileishmanial drugs unrelated to the sterol biosynthesis pathway, such as trivalent antimony and pentamidine, was similar to that of the wild-type strain; however, LaSimR was cross-resistant to miltefosine, general serine protease inhibitor N-p-tosyl-l-phenylalanine chloromethyl ketone (TPCK), subtilisin-specific inhibitor 4-[(diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-(3R)-3-pyrrolidinyl-benzamide dihydrochloride (PF-429242), and tunicamycin. The findings on the regulation of the sterol pathway can support the development of drugs and protease inhibitors targeting this route in parasites.
15
Smith, L. L., N. M. Made Gowda, and J. I. Teng. "Metabolism of sterol hyoroperoxides." Journal of Steroid Biochemistry 25 (January 1986): 7. http://dx.doi.org/10.1016/0022-4731(86)90480-2.
16
Poirot, Marc. "Sterol metabolism and cancer." Biochemical Pharmacology 196 (February 2022): 114843. http://dx.doi.org/10.1016/j.bcp.2021.114843.
17
Hölttä-Vuori, M., and E. Ikonen. "Endosomal cholesterol traffic: vesicular and non-vesicular mechanisms meet." Biochemical Society Transactions 34, no. 3 (May 22, 2006): 392–94. http://dx.doi.org/10.1042/bst0340392.
Анотація:
The endoplasmic reticulum is traditionally perceived as the key compartment for regulating intracellular cholesterol metabolism. Increasing evidence suggests that the endocytic pathway provides an additional regulatory level governing intracellular cholesterol trafficking and homoeostasis. Sterols can enter, and apparently also exit, endosomal compartments via both vesicular and non-vesicular mechanisms. A number of studies have focused on endosomal sterol removal as its defects lead to cholesterol storage diseases. So far, the bulk of evidence on endosomal sterol egress describes the involvement of membrane trafficking machineries. Interestingly, two late endosomal sterol-binding proteins were recently shown to regulate the movement of late endosomes along cytoskeletal tracks. These studies provide the first indications of how non-vesicular and vesicular mechanisms may co-operate in endosomal sterol trafficking.
18
Chakrabarti, Priyadarshini, Hannah M. Lucas, and Ramesh R. Sagili. "Novel Insights into Dietary Phytosterol Utilization and Its Fate in Honey Bees (Apis mellifera L.)." Molecules 25, no. 3 (January 28, 2020): 571. http://dx.doi.org/10.3390/molecules25030571.
Анотація:
Poor nutrition is an important factor in global bee population declines. A significant gap in knowledge persists regarding the role of various nutrients (especially micronutrients) in honey bees. Sterols are essential micronutrients in insect diets and play a physiologically vital role as precursors of important molting hormones and building blocks of cellular membranes. Sterol requirements and metabolism in honey bees are poorly understood. Among all pollen sterols, 24-methylenecholesterol is considered the key phytosterol required by honey bees. Nurse bees assimilate this sterol from dietary sources and store it in their tissues as endogenous sterol, to be transferred to the growing larvae through brood food. This study examined the duration of replacement of such endogenous sterols in honey bees. The dietary 13C-labeled isotopomer of 24-methylenecholesterol added to artificial bee diet showed differential, progressive in vivo assimilation across various honey bee tissues. Significantly higher survival, diet consumption, head protein content and abdominal lipid content were observed in the dietary sterol-supplemented group than in the control group. These findings provide novel insights into phytosterol utilization and temporal pattern of endogenous 24-methylenecholesterol replacement in honey bees.
19
de Saint-Jean, Maud, Vanessa Delfosse, Dominique Douguet, Gaëtan Chicanne, Bernard Payrastre, William Bourguet, Bruno Antonny, and Guillaume Drin. "Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers." Journal of Cell Biology 195, no. 6 (December 12, 2011): 965–78. http://dx.doi.org/10.1083/jcb.201104062.
Анотація:
Osh/Orp proteins transport sterols between organelles and are involved in phosphoinositide metabolism. The link between these two aspects remains elusive. Using novel assays, we address the influence of membrane composition on the ability of Osh4p/Kes1p to extract, deliver, or transport dehydroergosterol (DHE). Surprisingly, phosphatidylinositol 4-phosphate (PI(4)P) specifically inhibited DHE extraction because PI(4)P was itself efficiently extracted by Osh4p. We solve the structure of the Osh4p–PI(4)P complex and reveal how Osh4p selectively substitutes PI(4)P for sterol. Last, we show that Osh4p quickly exchanges DHE for PI(4)P and, thereby, can transport these two lipids between membranes along opposite routes. These results suggest a model in which Osh4p transports sterol from the ER to late compartments pinpointed by PI(4)P and, in turn, transports PI(4)P backward. Coupled to PI(4)P metabolism, this transport cycle would create sterol gradients. Because the residues that recognize PI(4)P are conserved in Osh4p homologues, other Osh/Orp are potential sterol/phosphoinositol phosphate exchangers.
20
GINGER, Michael L., Michael L. CHANCE, and L. John GOAD. "Elucidation of carbon sources used for the biosynthesis of fatty acids and sterols in the trypanosomatid Leishmania mexicana." Biochemical Journal 342, no. 2 (August 24, 1999): 397–405. http://dx.doi.org/10.1042/bj3420397.
Анотація:
Sterols are necessary for the growth of trypanosomatid protozoans; sterol biosynthesis is a potential target for the use and development of drugs to treat the diseases caused by these organisms. This study has used 14C-labelled substrates to investigate the carbon sources utilized by promastigotes and amastigotes of Leishmania mexicana for the production of sterol [mainly ergosta-5,7,24(241)-trien-3β-ol] and the fatty acid moieties of the triacylglycerol (TAG) and phospholipid (PL) of the organism. The isoprenoid precursor mevalonic acid (MVA) was incorporated into the sterols, and the sterol precursor squalene, by the promastigotes of L. mexicana. However, acetate (the precursor to MVA in most organisms) was a very poor substrate for sterol production but was readily incorporated into the fatty acids of TAG and PL. Other substrates (glucose, palmitic acid, alanine, serine and isoleucine), which are metabolized to acetyl-CoA, were also very poor precursors to sterol but were incorporated into TAG and PL and gave labelling patterns of the lipids similar to those of acetate. In contrast, the amino acid leucine was the only substrate to be incorporated efficiently into the squalene and sterol of L. mexicana promastigotes. Quantitative measurements revealed that at least 70-80% of the sterol synthesized by the promastigotes of L. mexicana is produced from carbon provided by leucine metabolism. Studies with the amastigote form of L. mexicana showed that in this case leucine was again the major sterol precursor, whereas acetate was utilized for fatty acid production.
21
Tiwari, Pragya, Rajender Singh Sangwan, Asha, B. N. Mishra, Farzana Sabir, and Neelam S. Sangwan. "Molecular Cloning and Biochemical Characterization of a Recombinant Sterol 3-O-Glucosyltransferase fromGymnema sylvestreR.Br. Catalyzing Biosynthesis of Steryl Glucosides." BioMed Research International 2014 (2014): 1–14. http://dx.doi.org/10.1155/2014/934351.
Анотація:
Gymnema sylvestreR.Br., a pharmacologically important herb vernacularly called Gur-Mar (sugar eliminator), is widely known for its antidiabetic action. This property of the herb has been attributed to the presence of bioactive triterpene glycosides. Although some information regarding pharmacology and phytochemical profiles of the plant are available, no attempts have been made so far to decipher the biosynthetic pathway and key enzymes involved in biosynthesis of steryl glucosides. The present report deals with the identification and catalytic characterization of a glucosyltransferase, catalyzing biosynthesis of steryl glycosides. The full length cDNA (2572 bp) contained an open reading frame of 2106 nucleotides that encoded a 701 amino acid protein, falling into GT-B subfamily of glycosyltransferases. The GsSGT was expressed inEscherichia coliand biochemical characterization of the recombinant enzyme suggested its key role in the biosynthesis of steryl glucosides with catalytic preference for C-3 hydroxyl group of sterols. To our knowledge, this pertains to be the first report on cloning and biochemical characterization of a sterol metabolism gene fromG. sylvestreR.Br. catalyzing glucosylation of a variety of sterols of biological origin from diverse organisms such as bacteria, fungi, and plants.
22
Hall, Rasheeda, Alyssa Platt, Jonathan Wilson, Patti L. Ephraim, Angelina S. Hwang, Angel Chen, Daniel E. Weiner, L. Ebony Boulware, Jane Pendergast, and Julia J. Scialla. "Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States." Clinical Journal of the American Society of Nephrology 15, no. 11 (October 12, 2020): 1603–13. http://dx.doi.org/10.2215/cjn.04350420.
Анотація:
Background and objectivesWith multiple medications indicated for mineral metabolism, dialysis providers can apply various strategies to achieve target phosphate and parathyroid hormone (PTH) levels. We describe common prescribing patterns and practice variation in mineral metabolism treatment strategies over the last decade.Design, setting, participants, & measurementsIn a cohort of adults initiating hemodialysis at Dialysis Clinic, Inc. facilities, we assessed prescriptions of vitamin D sterols, phosphate binders, and cinacalcet longitudinally. To identify the influence of secular trends in clinical practice, we stratified the cohort by dialysis initiation year (2006–2008, 2009–2011, and 2012–2015). To measure practice variation, we estimated the median odds ratio for prescribing different mineral metabolism treatment strategies at 12 months post–dialysis initiation across facilities using mixed effects multinomial logistic regression. Sensitivity analyses evaluated strategies used after detection of first elevated PTH.ResultsAmong 23,549 incident patients on hemodialysis, there was a decline in vitamin D sterol–based strategies and a corresponding increase in strategies without PTH-modifying agents (i.e., phosphate binders alone or no mineral metabolism medications) and cinacalcet-containing treatment strategies between 2006 and 2015. The proportion with active vitamin D sterol–based strategies at dialysis initiation decreased across cohorts: 15% (2006–2008) to 5% (2012–2015). The proportion with active vitamin D sterol–based strategies after 18 months of dialysis decreased across cohorts: 52% (2006–2008) to 34% (2012–2015). The odds of using individual strategies compared with reference (active vitamin D sterol with phosphate binder) varied from 1.5- to two-fold across facilities in 2006–2008 and 2009–2011 cohorts, and increased to two- to three-fold in the 2012–2015 cohort. Findings were similar in sensitivity analyses starting from first elevated PTH measurement.ConclusionsOver time, mineral metabolism management involved less use of vitamin D sterol–based strategies, greater use of both more conservative and cinacalcet-containing strategies, and increased practice variation, suggesting growing equipoise.
23
Hartmann, M. A., L. Wentzinger, A. Hemmerlin, and T. J. Bach. "Metabolism of farnesyl diphosphate in tobacco BY-2 cells treated with squalestatin." Biochemical Society Transactions 28, no. 6 (December 1, 2000): 794–96. http://dx.doi.org/10.1042/bst0280794.
Анотація:
Plant isoprenoids represent a large group of compounds with a wide range of physiological functions. In the cytosol, isoprenoids are synthesized via the classical acetate/mevalonate pathway. In this pathway, farnesyl diphosphate (FPP) occupies a central position, from which isoprene units are dispatched to the different classes of isoprenoids, with sterols as the major end products. The present work deals with effects of squalestatin (SQ) on the metabolism of FPP in proliferating and synchronized cultured tobacco cv. Bright Yellow-2 cells. SQ is a potent inhibitor of squalene synthase (SQS), the first committed enzyme in the sterol pathway. At nanomolar concentrations, SQ severely impaired cell growth and sterol biosynthesis, as attested by the rapid decrease in SQS activity. At the same time, it triggered a several-fold increase in both the enzymic activity and mRNA levels of 3-hydroxy-3-methylglutaryl CoA reductase. When SQ was added to cells synchronized by aphidicolin treatment, it was found to block the cell cycle at the end of G1 phase, but no cell death was induced. Tobacco cells were also fed exogenous tritiated trans-trans farnesol, the allylic alcohol derived from FPP, in the presence and absence of SQ. Evidence is presented that this compound was incorporated into sterols and ubiquinone Q10. In the presence of SQ, the sterol pathway was inhibited, but no increase in the radioactivity of ubiquinone was observed, suggesting that this metabolic channel was already saturated under normal conditions.
24
Crick, Peter J., T. William Bentley, Jonas Abdel-Khalik, Ian Matthews, Peter T. Clayton, Andrew A. Morris, Brian W. Bigger, et al. "Quantitative Charge-Tags for Sterol and Oxysterol Analysis." Clinical Chemistry 61, no. 2 (February 1, 2015): 400–411. http://dx.doi.org/10.1373/clinchem.2014.231332.
Анотація:
Abstract BACKGROUND Global sterol analysis is challenging owing to the extreme diversity of sterol natural products, the tendency of cholesterol to dominate in abundance over all other sterols, and the structural lack of a strong chromophore or readily ionized functional group. We developed a method to overcome these challenges by using different isotope-labeled versions of the Girard P reagent (GP) as quantitative charge-tags for the LC-MS analysis of sterols including oxysterols. METHODS Sterols/oxysterols in plasma were extracted in ethanol containing deuterated internal standards, separated by C18 solid-phase extraction, and derivatized with GP, with or without prior oxidation of 3β-hydroxy to 3-oxo groups. RESULTS By use of different isotope-labeled GPs, it was possible to analyze in a single LC-MS analysis both sterols/oxysterols that naturally possess a 3-oxo group and those with a 3β-hydroxy group. Intra- and interassay CVs were <15%, and recoveries for representative oxysterols and cholestenoic acids were 85%–108%. By adopting a multiplex approach to isotope labeling, we analyzed up to 4 different samples in a single run. Using plasma samples, we could demonstrate the diagnosis of inborn errors of metabolism and also the export of oxysterols from brain via the jugular vein. CONCLUSIONS This method allows the profiling of the widest range of sterols/oxysterols in a single analytical run and can be used to identify inborn errors of cholesterol synthesis and metabolism.
25
Bay, Denice C., Joe D. O’Neil, and Deborah A. Court. "The influence of sterols on the conformation of recombinant mitochondrial porin in detergent." Biochemistry and Cell Biology 86, no. 6 (December 2008): 539–45. http://dx.doi.org/10.1139/o08-132.
Анотація:
Mitochondrial porins (voltage-dependent anion-selective channels, VDAC) are key contributors to cellular metabolism. When isolated from mitochondria porins copurify with sterols, and some isolated forms of the protein require sterol for insertion into artificial membranes. Nonetheless, the contributions of sterols to the folded state of mitochondrial porin are not understood. Recently, with the goal of high-resolution structural studies, several laboratories have developed methods for folding recombinant porins at high concentration in detergent. In the present study, recombinant Neurospora crassa porin solubilized in detergent–sterol mixtures was examined. Sterols do not significantly alter the secondary structure of porin in lauryl dimethylamine oxide, nor in a mixture of sodium dodecylsulfate and dodecylmaltopyranoside. However, as detected by near-UV circular dichroism spectropolarimetry and fluorescence spectroscopy, the environments surrounding the aromatic amino acids in the detergent–sterol solubilized protein are measurably different from those in detergent alone. Furthermore, the effects are different in the presence of ergosterol, the native sterol in fungal mitochondria, and cholesterol. While these influences on the tertiary arrangement of detergent-solubilized porin are subtle, they may contribute to the generation of a form of the protein competent for insertion into the artificial bilayers used for electrophysiological analyses, and should be considered in future structural studies of porin.
26
Haas, Dorothea, and Maximilian Muenke. "Abnormal sterol metabolism in holoprosencephaly." American Journal of Medical Genetics Part C: Seminars in Medical Genetics 154C, no. 1 (February 15, 2010): 102–8. http://dx.doi.org/10.1002/ajmg.c.30243.
27
Sato, Ryuichiro. "Sterol metabolism and SREBP activation." Archives of Biochemistry and Biophysics 501, no. 2 (September 2010): 177–81. http://dx.doi.org/10.1016/j.abb.2010.06.004.
28
Svoboda, James A., and Mark F. Feldlaufer. "Neutral sterol metabolism in insects." Lipids 26, no. 8 (August 1991): 614–18. http://dx.doi.org/10.1007/bf02536425.
29
Zhu, Qian, Jingjing Wu, Daxue He, and Xuemei Lian. "Effects of Plant Sterols Intake on Systematic and Tissue Specific Lipid Metabolism in C57BL/6J Mice." Current Developments in Nutrition 5, Supplement_2 (June 2021): 388. http://dx.doi.org/10.1093/cdn/nzab037_098.
Анотація:
Abstract Objectives To investigate the effects of plant sterols intake on systematic and tissue specific lipid metabolism in C57BL/6J mice. Methods Male C57BL/6J mice were randomly divided into control diet group (CS) and plant sterol group (PS, 2% plant sterols). After 28 weeks of continuous feeding, the serum of the mice were collected for biochemical and mass spectrometry tests. Serum levels of total cholesterol (TC), triglyceride (TG) and free sterols were determined. The livers and lungs were collected for free sterol quantification and RNA-seq analysis. Results Compared with the CS group, 2% plant sterols intake significantly reduced the levels of TC in the serum of mice (P < 0.05), with the TG level unchanged. The quantitative results of free sterols showed that the concentration of campesterol were increased, and the cholestanol levels were decreased significantly in the serum and liver of the PS group mice. The results of RNA-seq analysis were used to further evaluate its impact on the lipid metabolism related gene expression profile in the livers and lungs. The results showed that HMGCR, SQLE, HMGCS1, SREBF1, and other genes related to cholesterol synthesis in the PS group were significantly up-regulated in the liver, but not in the lung; Among the first 20 targeting pathways related to the action of plant sterols, the liver differentially expressed genes were enriched in lipid metabolism (steroid biosynthesis, terpenoid skeleton biosynthesis, peroxisome, bile acid secretion, PPAR, MAPK, fatty acid metabolism.), inflammation related (Cell adhesion molecules, leukocyte trans-endothelial migration) and amino acid metabolism (glutathione, valine, leucine and isoleucine metabolism). The differential genes in lung tissue are enriched in lipid metabolism (acetone metabolism, fatty acid metabolism, insulin resistance, terpenoid skeleton biosynthesis, iron death, PPAR), cell function (internal Swallowing, aging) and vascular smooth muscle contraction etc. Conclusions Differentially expressed gene networks reflect the multi-dimensional regulation of plant sterols on tissue specific lipid metabolism, which lays a good foundation for further revealing its mechanism. Funding Sources Yihaikerry Nutrition and Food Safety Foundation, Chinese Nutrition Society; Project of Technology Innovation and Application, Chongqing, China
30
Bay, Denice C., and Deborah A. Court. "Effects of ergosterol on the structure and activity of Neurospora mitochondrial porin in liposomes." Canadian Journal of Microbiology 55, no. 11 (November 2009): 1275–83. http://dx.doi.org/10.1139/w09-088.
Анотація:
Mitochondrial porins (also known as voltage-dependent anion-selective channels (VDACs)) regulate and contribute to cellular metabolism. These proteins copurify with sterols, and some purified forms of the protein require sterol for insertion into planar artificial membranes. Recently, interactions between detergent-solubilized mitochondrial porins and sterols have been detected by NMR and spectroscopic methods, but the effects of sterols on pore function remained to be assessed. Therefore, in this work, a freeze–thaw technique was used to introduce recombinant Neurospora porin into liposomes containing, or lacking, the native fungal sterol ergosterol. In both types of liposomes, insertion of the protein converts it to a protease-resistant state and low levels of dimeric and trimeric forms are observed. There are only minor differences between the secondary structural components of the protein in the presence or absence of sterol. Ergosterol in proteoliposomes alters their osmotic responses to sucrose, possibly due to increased membrane rigidity or interactions with the protein that were not revealed by the methods used in this study. The presence of ergosterol is associated with an increased change in conformation and loss of function of liposome-embedded porin at high temperature. Taken with other evidence for direct interactions of sterols with porins, these results support a link between these two molecules in mitochondrial membrane activity.
31
Moehninsi, Iris Lange, B. Markus Lange, and Duroy A. Navarre. "Altering potato isoprenoid metabolism increases biomass and induces early flowering." Journal of Experimental Botany 71, no. 14 (April 16, 2020): 4109–24. http://dx.doi.org/10.1093/jxb/eraa185.
Анотація:
Abstract Isoprenoids constitute the largest class of plant natural products and have diverse biological functions including in plant growth and development. In potato (Solanum tuberosum), the regulatory mechanism underlying the biosynthesis of isoprenoids through the mevalonate pathway is unclear. We assessed the role of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) homologs in potato development and in the metabolic regulation of isoprenoid biosynthesis by generating transgenic lines with down-regulated expression (RNAi-hmgr) or overexpression (OE) of one (StHMGR1 or StHMGR3) or two genes, HMGR and farnesyl diphosphate synthase (FPS; StHMGR1/StFPS1 or StHMGR3/StFPS1). Levels of sterols, steroidal glycoalkaloids (SGAs), and plastidial isoprenoids were elevated in the OE-HMGR1, OE-HMGR1/FPS1, and OE-HMGR3/FPS1 lines, and these plants exhibited early flowering, increased stem height, increased biomass, and increased total tuber weight. However, OE-HMGR3 lines showed dwarfism and had the highest sterol amounts, but without an increase in SGA levels, supporting a rate-limiting role for HMGR3 in the accumulation of sterols. Potato RNAi-hmgr lines showed inhibited growth and reduced cytosolic isoprenoid levels. We also determined the relative importance of transcriptional control at regulatory points of isoprenoid precursor biosynthesis by assessing gene–metabolite correlations. These findings provide novel insights into specific end-products of the sterol pathway and could be important for crop yield and bioenergy crops.
32
Wilbrink, M. H., M. Petrusma, L. Dijkhuizen, and R. van der Geize. "FadD19 of Rhodococcus rhodochrous DSM43269, a Steroid-Coenzyme A Ligase Essential for Degradation of C-24 Branched Sterol Side Chains." Applied and Environmental Microbiology 77, no. 13 (May 20, 2011): 4455–64. http://dx.doi.org/10.1128/aem.00380-11.
Анотація:
ABSTRACTThe actinobacterial cholesterol catabolic gene cluster contains a subset of genes that encode β-oxidation enzymes with a putative role in sterol side chain degradation. We investigated the physiological roles of several genes, i.e.,fadD17,fadD19,fadE26,fadE27, andro04690DSM43269, by gene inactivation studies in mutant strain RG32 ofRhodococcus rhodochrousDSM43269. Mutant strain RG32 is devoid of 3-ketosteroid 9α-hydroxylase (KSH) activity and was constructed following the identification, cloning, and sequential inactivation of fivekshAgene homologs in strain DSM43269. We show that mutant strain RG32 is fully blocked in steroid ring degradation but capable of selective sterol side chain degradation. Except for RG32ΔfadD19, none of the mutants constructed in RG32 revealed an aberrant phenotype on sterol side chain degradation compared to parent strain RG32. Deletion offadD19in strain RG32 completely blocked side chain degradation of C-24 branched sterols but interestingly not that of cholesterol. The additional inactivation offadD17in mutant RG32ΔfadD19also did not affect cholesterol side chain degradation. Heterologously expressed FadD19DSM43269nevertheless was active toward steroid-C26-oic acid substrates. Our data identified FadD19 as a steroid-coenzyme A (CoA) ligase with an essentialin vivorole in the degradation of the side chains of C-24 branched-chain sterols. This paper reports the identification and characterization of a CoA ligase with anin vivorole in sterol side chain degradation. The high similarity (67%) between the FadD19DSM43269and FadD19H37Rvenzymes further suggests that FadD19H37Rvhas anin vivorole in sterol metabolism ofMycobacterium tuberculosisH37Rv.
33
White, T. C., and P. M. Silver. "Regulation of sterol metabolism in Candida albicans by the UPC2 gene." Biochemical Society Transactions 33, no. 5 (October 26, 2005): 1215–18. http://dx.doi.org/10.1042/bst0331215.
Анотація:
Candida albicans is an important pathogenic fungus of humans, causing a range of infections. These infections are usually treated with antifungal drugs that target sterol metabolism. Resistance to these antifungals can result from overexpression of sterol biosynthetic genes. Therefore it is of interest to understand transcriptional regulation of sterol biosynthesis in C. albicans. Recently two reports [Silver, Oliver and White (2004) Eukaryot. Cell 3, 1391–1397; MacPherson, Akache, Weber, De Deken, Raymond and Turcotte (2005) Antimicrob. Agents Chemother. 49, 1745–1752] have identified and characterized a single C. albicans transcription factor gene UPC2 that regulates sterol metabolism. The details of both characterizations are compared and contrasted. These reports extend our understanding of sterol regulation in this important human pathogen.
34
Rogowska, Agata, Cezary Pączkowski, and Anna Szakiel. "Modulation of Steroid and Triterpenoid Metabolism in Calendula officinalis Plants and Hairy Root Cultures Exposed to Cadmium Stress." International Journal of Molecular Sciences 23, no. 10 (May 18, 2022): 5640. http://dx.doi.org/10.3390/ijms23105640.
Анотація:
The present study investigated the changes in the content of steroids and triterpenoids in C. officinalis hairy root cultures and plants exposed to cadmium stress. The observed effects included the content and composition of analyzed groups of compounds, particularly the proportions among individual sterols (e.g., stigmasterol-to-sitosterol ratio), their ester and glycoside conjugates. The total sterol content increased in roots (by 30%) and hairy root culture (by 44%), whereas it decreased in shoots (by 15%); moreover, these effects were inversely correlated with Cd-induced growth suppression. Metabolic alterations of sterols and their forms seemed to play a greater role in the response to Cd stress in roots than in shoots. The symptoms of the competition between general metabolites (sterols) and specialized metabolites (triterpenoids) were also observed, i.e., the increase of the sterol biosynthesis parallel to the decrease of the triterpenoid content in C. officinalis plant roots and hairy root culture, and the inverse phenomenon in shoots. The similarity of the metabolic modifications observed in the present study on C. officinalis plant roots and hairy roots confirmed the possibility of application of plant in vitro cultures in initial studies for physiological research on plant response to environmental stresses.
35
Jong, Ariënne de, Jogchum Plat, Dieter Lütjohann, and Ronald P. Mensink. "Effects of long-term plant sterol or stanol ester consumption on lipid and lipoprotein metabolism in subjects on statin treatment." British Journal of Nutrition 100, no. 5 (November 2008): 937–41. http://dx.doi.org/10.1017/s0007114508966113.
Анотація:
Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3–7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n18) or plant stanol (n19) (2·5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0·28 mmol/l (or 8·7 %;P = 0·08) and 0·42 mmol/l (13·1 %;P = 0·006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7α-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.
36
Sato, Ryuichiro. "Regulation of the intracellular sterol metabolism." Journal of Japan Atherosclerosis Society 28, no. 6 (2001): 127–32. http://dx.doi.org/10.5551/jat1973.28.6_127.
37
Salt, Thomas A., David J. Chitwood, and William R. Lusby. "Sterol metabolism in the nematodePanagrellus redivivus." Lipids 24, no. 4 (April 1989): 325–28. http://dx.doi.org/10.1007/bf02535171.
38
Wang, Yuqin, and William J. Griffiths. "Unravelling new pathways of sterol metabolism." Current Opinion in Clinical Nutrition & Metabolic Care 21, no. 2 (March 2018): 90–96. http://dx.doi.org/10.1097/mco.0000000000000442.
39
TESHIMA, SHIN-ICHI. "Metabolism of sterol in marine organisms." Kagaku To Seibutsu 25, no. 9 (1987): 601–9. http://dx.doi.org/10.1271/kagakutoseibutsu1962.25.601.
40
Smith, Leland L., N. M. Made Gowda, and Jon I. Teng. "Sterol hydroperoxide metabolism by Salmonella typhimurium." Journal of Steroid Biochemistry 26, no. 2 (February 1987): 259–64. http://dx.doi.org/10.1016/0022-4731(87)90080-x.
41
Yao, Lihang, and Laura A. Woollett. "Adult sterol metabolism is not affected by a positive sterol balance in the neonatal Golden Syrian hamster." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 288, no. 3 (March 2005): R561—R566. http://dx.doi.org/10.1152/ajpregu.00353.2004.
Анотація:
Dietary components impact metabolism early in life. Some of the diet-induced effects are long lasting and can lead to various adult-based diseases. In the current studies, we examined the short-term effects of dietary cholesterol on neonatal hepatic sterol metabolism and the long-term effects that those early-life diets had on sterol metabolism in adulthood. Neonatal hamsters began consuming solid food as a supplement to milk by 5 days of age; diets contained 0 or 2% added cholesterol (wt/wt). By 10 days of age, plasma and liver cholesterol concentrations were 3.2- and 2.5-fold greater, respectively, in the neonates fed cholesterol. Hepatic sterol synthesis rates were suppressed 65% in cholesterol-fed neonates compared with control neonates. By 20 days of age, plasma and liver cholesterol concentrations were still greater and sterol synthesis rates were now suppressed maximally in neonates fed cholesterol compared with control neonates. The expression level of an apolipoprotein B-containing lipoprotein receptor (low-density lipoprotein receptor-related protein) was greater and the mature form of the sterol regulatory element-binding protein-2 was similar in livers of 20-day-old control neonates compared with control neonates at 10 days of age. To test whether the change in sterol balance in the neonatal period had a lasting effect on hepatic sterol metabolism, all animals were weaned on a low-cholesterol diet. At 70 days of age, hepatic sterol synthesis rates, plasma lipoprotein and liver cholesterol concentrations, and bile acid pool sizes and compositions were measured. Sterol balance in the adults was similar between animals fed either diet early in life, as demonstrated by a lack of difference in any parameter measured. Thus, even though dietary cholesterol suppressed hepatic sterol synthesis rates dramatically in the neonatal hamster, the change has little impact on sterol balance later in life.
42
Potocka, Anna, and Jan Zimowski. "Metabolism of conjugated sterols in eggplant. Part 1. UDP-glucose : sterol glucosyltransferase." Acta Biochimica Polonica 55, no. 1 (January 16, 2008): 127–34. http://dx.doi.org/10.18388/abp.2008_3105.
Анотація:
A membrane-bound UDP-glucose : sterol glucosyltransferase from Solanum melongena (eggplant) leaves was partially purified and its specificity as well as molecular and kinetic properties were defined. Among a wide spectrum of 3-OH steroids (i.e. typical plant sterols, androstane, pregnane and cholestane derivatives, steroidal alkaloids and sapogenins) and triterpenic alcohols, the highest activity was found with 22-oxycholesterol. UDP-glucose appeared to be the best sugar donor. The enzyme preparation was also able to utilize UDP-galactose, TDP-glucose and CDP-glucose as a sugar source for sterol glucosylation, however, at distinctly lower rates. The investigated glucosyltrasferase was stimulated by 2-mercaptoethanol, Triton X-100 and negatively charged phospholipids, and inhibited in the presence of UDP, mono-, di- and triacylglycerols, divalent cations such as Zn(2+), Co(2+), high ionic strength, cholesteryl glucoside, galactoside and xyloside and some amino acid-modifying reagents (SITS, DIDS, PLP, DEPC, pCMBS, NEM, WRK and HNB). Our results suggest that unmodified residues of lysine, tryptophan, cysteine, histidine and dicarboxylic amino acids are essential for full enzymatic activity and indicate that a glutamic (or aspartic) acid residue is necessary for the binding of sugar donor, i.e. UDP-glucose in the active site of the GT-ase while histidine and cysteine residues are both important for the binding of the nucleotide-sugar as well as of the steroidal aglycone.
43
Malvoisin, E., F. Wild, and G. Zwingelstein. "Relationship between membrane sterol composition and responsiveness to 12-O-tetradecanoylphorbol 13-acetate in HL-60 human promyelocytic leukaemia cell lines." Biochemical Journal 250, no. 2 (March 1, 1988): 349–53. http://dx.doi.org/10.1042/bj2500349.
Анотація:
We have examined the sterol composition and metabolism of promyelocytic leukaemia cell lines (HL-60) after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). A variant cell line (Blast II cells) which is resistant to TPA was used as control. Analysis of the sterols of TPA-sensitive cells radiolabelled with [3H]leucine, [14C]acetate or [14C]pyruvate showed a high incorporation into cholesterol and a low incorporation in lanosterol + dihydrolanosterol. The inverse relationship was observed in TPA-resistant cells. Experiments with other cellular variants representing TPA-sensitive and TPA-resistant classes gave similar results. Analysis of the cellular sterol composition by gas chromatography confirmed that TPA-resistant cells are particularly rich in lanosterol/dihydrolanosterol. TPA treatment enhanced the incorporation of [14C]pyruvate into the sterol fraction of both cell types. This was accompanied by an alteration of incorporation into several lipids, particularly phospholipids. Pulse-chase studies with [14C]acetate revealed that TPA induced the release of radioactive lipids into the medium from HL-60 and Blast II cells. However this treatment released phospholipids from the TPA-sensitive cells and sterols and fatty acids from the TPA-resistant cells. We conclude that the sterol composition can regulate specific biochemical processes in the membrane and can be considered as a factor that plays a role in the responsiveness of HL-60 cells to TPA.
44
Matysik, S., HH Klünemann, and G. Schmitz. "Gas Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of Oxysterols, Plant Sterols, and Cholesterol Precursors." Clinical Chemistry 58, no. 11 (November 1, 2012): 1557–64. http://dx.doi.org/10.1373/clinchem.2012.189605.
Анотація:
BACKGROUND Cholesterol precursors and plant sterols have considerable potential as plasma biomarkers in several disorders of sterol metabolism and intestinal sterol absorption. Oxysterols are associated with atherogenesis, neurodegeneration, and inflammation. We developed a GC-MS method for the simultaneous analysis of these species in human plasma, including 24-, 25-, 27-hydroxycholesterol; 7-ketocholesterol; lanosterol; lathosterol; 7-dehydrocholesterol; desmosterol; stigmasterol; sitosterol; and campesterol. METHODS Sterols were hydrolyzed with ethanolic potassium hydroxide solution, extracted by liquid/liquid extraction with n-hexane, and derivatized with N-methyl-N-trimethylsilyl-trifluoracetamide. Positive chemical ionization with ammonia, as reagent gas, was applied to generate high abundant precursor ions. RESULTS The definition of highly sensitive precursor/product ion transitions, especially for coeluting substances, allowed fast gas chromatography run times of under 8.5 min. Using the multiple reaction monitoring mode, detection limits in the picogram per milliliter range could be achieved for most compounds. The method was validated for precision and recovery. Intraassay and interassay CVs were mostly <15% for serum and plasma samples. The recoveries of supplemented plasma samples in different concentrations were 88%–117%. The method was applied to stratification of patients with disorders in cholesterol biosynthesis and/or cholesterol absorption in hypercholesterolemia. The method revealed associations of sterol species with thyroid dysfunction and type 2 diabetes. CONCLUSIONS This method allows high-throughput sterol profiling in various diseases.
45
Rogowska, Agata, and Anna Szakiel. "Enhancement of Phytosterol and Triterpenoid Production in Plant Hairy Root Cultures—Simultaneous Stimulation or Competition?" Plants 10, no. 10 (September 27, 2021): 2028. http://dx.doi.org/10.3390/plants10102028.
Анотація:
Plant in vitro cultures, including hairy roots, can be applied for controlled production of valuable natural products, such as triterpenoids and sterols. These compounds originate from the common precursor squalene. Sterols and triterpenoids distinctly differ in their functions, and the 2,3-oxidosqualene cyclization step is often regarded as a branch point between primary and secondary (more aptly: general and specialized) metabolism. Considering the crucial role of phytosterols as membrane constituents, it has been postulated that unconstrained biosynthesis of triterpenoids can occur when sterol formation is already satisfied, and these compounds are no longer needed for cell growth and division. This hypothesis seems to follow directly the growth-defense trade-off plant dilemma. In this review, we present some examples illustrating the specific interplay between the two divergent pathways for sterol and triterpenoid biosynthesis appearing in root cultures. These studies were significant for revealing the steps of the biosynthetic pathway, understanding the role of particular enzymes, and discovering the possibility of gene regulation. Currently, hairy roots of many plant species can be considered not only as an efficient tool for production of phytochemicals, but also as suitable experimental models for investigations on regulatory mechanisms of plant metabolism.
46
Lutova, Ludmila A., and Galina M. Shumilina. "Metabolites of plants and their role in resistance to phytopathogens." Ecological genetics 1, no. 1 (January 15, 2003): 47–58. http://dx.doi.org/10.17816/ecogen1047-58.
Анотація:
Plant disease resistance is a complex reaction where biochemical peculiarities play a major role. The review is focused on two strategies of improvement of plant resistance to some groups of pathogens. The first strategy is based on a dependence of pathogens on certain plant compounds, i.e. sterols. The lack of these metabolites in a host plant repress pathogen development and reproduction. Here we present modern data on sterol metabolism and their functions in plants as well as description of known plant sterol mutants. The other way to improve plant resistance is to stimulate biosynthesis of secondary metabolites with antimicrobial activity. The roles of phytoalexins and steroid glycoalcoloids in the development of plant resistance is described here on certain examples
47
Jordá, Tania, and Sergi Puig. "Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae." Genes 11, no. 7 (July 15, 2020): 795. http://dx.doi.org/10.3390/genes11070795.
Анотація:
Ergosterol is an essential component of fungal cell membranes that determines the fluidity, permeability and activity of membrane-associated proteins. Ergosterol biosynthesis is a complex and highly energy-consuming pathway that involves the participation of many enzymes. Deficiencies in sterol biosynthesis cause pleiotropic defects that limit cellular proliferation and adaptation to stress. Thereby, fungal ergosterol levels are tightly controlled by the bioavailability of particular metabolites (e.g., sterols, oxygen and iron) and environmental conditions. The regulation of ergosterol synthesis is achieved by overlapping mechanisms that include transcriptional expression, feedback inhibition of enzymes and changes in their subcellular localization. In the budding yeast Saccharomyces cerevisiae, the sterol regulatory element (SRE)-binding proteins Upc2 and Ecm22, the heme-binding protein Hap1 and the repressor factors Rox1 and Mot3 coordinate ergosterol biosynthesis (ERG) gene expression. Here, we summarize the sterol biosynthesis, transport and detoxification systems of S. cerevisiae, as well as its adaptive response to sterol depletion, low oxygen, hyperosmotic stress and iron deficiency. Because of the large number of ERG genes and the crosstalk between different environmental signals and pathways, many aspects of ergosterol regulation are still unknown. The study of sterol metabolism and its regulation is highly relevant due to its wide applications in antifungal treatments, as well as in food and pharmaceutical industries.
48
Friedman, Susan J., Stanley Cheng, and Philip Skehan. "Mechanisms of cholesterol synthesis inhibition by D-glucosamine." Canadian Journal of Biochemistry and Cell Biology 63, no. 12 (December 1, 1985): 1253–57. http://dx.doi.org/10.1139/o85-157.
Анотація:
The amino sugar D-glucosamine possesses antitumor activity which is thought to depend in part upon its ability to impair cholesterol biosynthesis and damage cellular membranes. The present study examined the effect of glucosamine on acetate utilization for lipid and sterol synthesis in rat C6 glial tumor cells. At cytotoxic concentrations, the amino sugar inhibited [14C]acetate incorporation into nonesterified sterols and lipids but increased the flow of label into cholesteryl esters. A comparison of the rates of acetate utilization for glucosamine metabolism (N-acetylation) and sterol and lipid synthesis suggested that glucosamine might act by competing for a common cytosolic pool of acetyl CoA. The inhibition of lipid and sterol synthesis, however, remained constant over a wide range of extracellular acetate concentrations. These results suggest that, if glucosamine acts by restricting the supply of acetate for these biosynthetic processes, it probably inhibits a step prior to the formation of acetyl CoA. Alternative mechanisms are discussed.
49
Schumacher, Marc M., and Russell A. DeBose-Boyd. "Posttranslational Regulation of HMG CoA Reductase, the Rate-Limiting Enzyme in Synthesis of Cholesterol." Annual Review of Biochemistry 90, no. 1 (June 20, 2021): 659–79. http://dx.doi.org/10.1146/annurev-biochem-081820-101010.
Анотація:
The polytopic, endoplasmic reticulum (ER) membrane protein 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate, the key intermediate in the synthesis of cholesterol and many nonsterol isoprenoids including geranylgeranyl pyrophosphate (GGpp). Transcriptional, translational, and posttranslational feedback mechanisms converge on this reductase to ensure cells maintain a sufficient supply of essential nonsterol isoprenoids but avoid overaccumulation of cholesterol and other sterols. The focus of this review is mechanisms for the posttranslational regulation of HMG CoA reductase, which include sterol-accelerated ubiquitination and ER-associated degradation (ERAD) that is augmented by GGpp. We discuss how GGpp-induced ER-to-Golgi trafficking of the vitamin K2 synthetic enzyme UbiA prenyltransferase domain–containing protein-1 (UBIAD1) modulates HMG CoA reductase ERAD to balance the synthesis of sterol and nonsterol isoprenoids. We also summarize the characterization of genetically manipulated mice, which established that sterol-accelerated, UBIAD1-modulated ERAD plays a major role in regulation of HMG CoA reductase and cholesterol metabolism in vivo.
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Rakotomanga, M., S. Blanc, K. Gaudin, P. Chaminade, and P. M. Loiseau. "Miltefosine Affects Lipid Metabolism in Leishmania donovani Promastigotes." Antimicrobial Agents and Chemotherapy 51, no. 4 (January 22, 2007): 1425–30. http://dx.doi.org/10.1128/aac.01123-06.
Анотація:
ABSTRACT Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active antileishmanial drug. Transient HePC treatment of Leishmania donovani promastigotes at 10 μM significantly reduced the phosphatidylcholine content and enhanced the phosphatidylethanolamine (PE) content in parasite membranes, suggesting a partial inactivation of PE-N-methyltransferase. Phospholipase D activity did not seem to be affected by HePC. In addition, the enhancement of the lysophosphatidylcholine content could be ascribed to phospholipase A2 activation. Moreover, transient HePC treatment had no effect on the fatty acid alkyl chain length or the fatty acid unsaturation rate. Concerning sterols, we found a strong reduction of the C24 alkylated sterol content, and the enhancement of the cholesterol content could be the result of the HePC condensation effect with sterols. Because some of the effects observed after transient HePC treatment were different from those previously observed in HePC-resistant parasites, it could be hypothesized that continuous in vitro drug pressure induces the mechanisms of regulation in Leishmania lipid metabolism.