Hepatic entrapment of esterified cholesterol drives continual expansion of whole body sterol pool in lysosomal acid lipase-deficient mice
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Cholesteryl ester storage disease (CESD) results from loss-of-function mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). Hepatomegaly and deposition of esterified cholesterol (EC) in multiple organs ensue. The present studies quantitated rates of synthesis, absorption, and disposition of cholesterol, and whole body cholesterol pool size in a mouse model of CESD. In 50-day-old lal(-/-) and matching lal(+/+) mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal(-/-) mice sequestered cholesterol at an average rate of 3.2 mg·day(-1)·animal(-1). The proportion of the body sterol pool contained in the liver of the lal(-/-) mice was 64 vs. 6.3% in their lal(+/+) controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal(-/-) mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal(-/-) mice, whole liver cholesterol synthesis increased 10.2-fold, resulting in a 3.2-fold greater rate of whole animal sterol synthesis compared with their lal(+/+) controls. The rate of cholesterol synthesis in the lal(-/-) mice exceeded that in the lal(+/+) controls by 3.7 mg·day(-1)·animal(-1). Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal(-/-) mice, but their rate of neutral sterol excretion was 59% higher than in their lal(+/+) controls. Thus, in this model, the continual expansion of the body sterol pool is driven by the synthesis of excess cholesterol, primarily in the liver. Despite the severity of their disease, the median life span of the lal(-/-) mice was 355 days.Keywords:
Sterol O-acyltransferase
Ergosterol
Sterol O-acyltransferase
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A gene encoding a sterol ester-synthesizing enzyme was identified in Arabidopsis. The cDNA of the Arabidopsis gene At1g04010 (AtPSAT) was overexpressed in Arabidopsis behind the cauliflower mosaic virus 35S promoter. Microsomal membranes from the leaves of overexpresser lines catalyzed the transacylation of acyl groups from phosphatidylethanolamine to sterols. This activity correlated with the expression level of the AtPSAT gene, thus demonstrating that this gene encodes a phospholipid:sterol acyltransferase (PSAT). Properties of the AtPSAT were examined in microsomal fractions from the tissues of an overexpresser. The enzyme did not utilize neutral lipids, had the highest activity with phosphatidylethanolamine, had a 5-fold preference for the sn-2 position, and utilized both saturated and unsaturated fatty acids. Various sterols and sterol intermediates, including triterpenic precursors, were acylated by the PSAT, whereas other triterpenes were not. Sterol selectivity studies showed that the enzyme is activated by end product sterols and that sterol intermediates are preferentially acylated by the activated enzyme. This indicates that PSAT both regulates the pool of free sterols as well as limits the amount of free sterol intermediates in the membranes. Two T-DNA insertion mutants in the AtPSAT gene, with strongly reduced (but still measurable) levels of sterol esters in their tissues, had no detectable PSAT activity in the microsomal fractions, suggesting that Arabidopsis possess other enzyme(s) capable of acylating sterols. The AtPSAT is the only intracellular enzyme found so far that catalyzes an acyl-CoA-independent sterol ester formation. Thus, PSAT has a similar physiological function in plant cells as the unrelated acyl-CoA:sterol acyltransferase has in animal cells.
Phosphatidylethanolamine
Acyltransferases
Acyltransferases
Sterol O-acyltransferase
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Eukaryote
Sterol O-acyltransferase
Homeostasis
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A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p. Are2p, Aus1p, and Pdr11p, unlike the minor acyltransferase, Are1p, colocalize to sterol and sphingolipid-enriched, detergent-resistant microdomains (DRMs). Deletion of either ABC transporter results in Are2p relocalization to detergent-soluble membrane domains and a significant decrease (53-36%) in esterification of exogenous sterol. Similarly, in murine tissues, the SOAT1/Acat1 enzyme and activity localize to DRMs. This subcellular localization is diminished upon deletion of murine ABC transporters, such as Abcg1, which itself is DRM associated. We propose that the close proximity of sterol esterification and transport proteins to each other combined with their residence in lipid-enriched membrane microdomains facilitates rapid, high-capacity sterol transport and esterification, obviating any requirement for soluble intermediary proteins.
Sterol O-acyltransferase
Acyltransferases
Acyltransferases
Squalene monooxygenase
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ABSTRACT 24‐Ethylcholesterol, 24‐ethylcholesta‐5,7,22‐trienol, dihydrolanosterol, 24‐ethylcholesta‐7,22‐dienol, and 4‐methyl‐24‐ethylcholesta‐7,22‐dienol were identified in cultured Cephaleuros in small quantities. Cholesterol made up 19% of the total sterol. The principal sterol, making up 65% of the total sterol, was 4,24‐dimethylcholest‐7‐enol, a new algal sterol. This is the first report of this sterol as the principal sterol of any living organism.
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Sterols, especially cholesterol (Chl), are fundamental for animal survival. Insects lacking the ability to synthesize Chl are sterol auxotrophic animals and utilize dietary Chl and phytosterols to survive. The sterols obtained from a diet are distributed to the tissues; however, sterol homeostasis in insect tissues remains to be elucidated. This study sought to understand the sterol characteristics of insect tissues through detailed sterol quantification and statistics. The combination of sterol quantification using liquid chromatography tandem mass spectrometry (LC-MS/MS) and principal component analysis (PCA) revealed tissue-specific sterol characteristics in the silkworm, Bombyx mori, a phytophagous insect. We found that insect tissues have tissue-intrinsic sterol profiles. The brain has a unique sterol composition as compared to other tissues-high concentration of Chl and less accumulation of phytosterols. Other tissues also have intrinsic sterol characteristics, which when defined by dietary sterols or Chl metabolites, indicate preference for a sterol and consistently manage their own sterol homeostasis. Though most tissues never change sterol profiles during development, the brain drastically changes its sterol profile at the wandering stage, indicating that it could alter sterol composition in preparation for metamorphosis. These results suggest the existence of tissue- and sterol-specific systems for sterol homeostasis in insects.
Phytosterol
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Abstract Twenty‐six sterols were isolated from eggs, larvae, workers, and queens of the red imported fire ant, Solenopsis invicta Buren. They were identified by chromatographic (TLC, GLC, and HPLC) and spectral methods (MS and 1 H‐NMR). Queens possessed the most varied sterol composition (24 sterols were detected). The major sterols from queens were the doubly bioalkylated 24α‐ethyl cholest‐5‐ and 7‐en‐3β‐ols whereas the major sterol from the other developmental stages was cholesterol, a sterol which lacks a C‐24 alkyl group. From fourth instar larvae were isolated two yeasts, Candida parapsilosis and Yarrowia lipolytica . Both yeasts were found to synthesize similar sterols, primarily ergosterol and zymosterol (90% of the sterol mixture). A minor sterol (approximately 12% of the total sterol mixture) detected in eggs, larvae, and workers was 24‐methyl cholesta‐5,22E‐dien‐3β‐ol (brassicasterol). Brassicasterol may have originated from ergosterol produced by the fungal endosymbiotes. The amount of sterol in each developmental stage was as follows: approximately 24 μg sterol/queen, 3 μg sterol/worker, 2 μg sterol/larvae, and 0.02 μg sterol/egg. The sterol composition of the red imported fire ant differed from that of leaf‐cutting ants previously investigated where 24‐methyl sterols of ectosymbiotic fungal origin were the major sterols detected in soldiers and workers. © 1995 Wiley‐Liss, Inc.
Ergosterol
Stigmasterol
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Sterol O-acyltransferase
Cholestanol
Stigmasterol
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참기름中 不감貨物은 RWE가 3.1%이고 RTE는 2.6%이며 全 sterol은 RTP가 0.68%이고 RTE가 0.48%이며 全 sterol中 free sterol이 37.9 (RTP)~52.7%(RTE)로서 sterylglycoside 및 sterylester보다 그 含量이 많다. 참기름中 total sterol의 구성 sterol組成은 39.3~42.9%의 sitosterol, 13.0~17.2%의 △^5-avenasterol, 9.1~11.0%의 campesterol 및 7.4~11.5%의 stigmasterol이며 23.5~24.6%의 未知sterol (RRT:1.35)도 含有되어 있었고 sterylglycoside는 total sterol의 sterol組成과 거의 같은 傾向이었으나 free sterol과 sterylester는 △^5-avenasterol이 8.1~11.4%로서 campesterol 및 stigmasterol보다 含有比가 낮았다. 한편 採油方法別 sterol組成은 差異가 거의 없었다.
Stigmasterol
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The article is concerned with the modification of lipase with Tween-80. We can use formaldehyde or glutaraldehyde to connect Tween-80 and lipase covalently. Comparing the difference between modified lipase and nature lipase, we can get some conclusion. The results are follows: with the same concentration of formaldehyde and glutaraldehyde, the activity of lipase modified by formaldehyde is higher than lipase which was modified by glutaraldehyde; while the lipase modified by glutaraldehyde has higher connecting efficiency than lipase modified by formaldehyde. With the different concentration of formaldehyde, the modified lipase has the highest activity when the concentration of formaldehyde is 1. 25 mg · mL-1. When the pH of phosphate is higher than 7, the modified lipase has higher activity; when the pH of phosphate is lower than 7, the nature lipase has higher activity.
Glutaraldehyde
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