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High-temperature GC-MS-based serum cholesterol signatures may reveal sex differences in vasospastic angina.

Son HH, Moon JY, Seo HS, Kim HH, Chung BC, Choi MH - J. Lipid Res. (2013)

Bottom Line: Linearity as the correlation coefficient was higher than 0.99 with the exception of cholesteryl laurate, myristate, oleate, and linoleate (r² > 0.98).The precision (% coefficient of variation) and accuracy (% bias) ranged from 1.1 to 9.8% and from 75.9 to 125.1%, respectively.The overall recoveries of CEs ranged from 26.1 to 64.0%, and the recoveries of other sterols ranged from 83.8 to 129.3%.

View Article: PubMed Central - PubMed

Affiliation: Future Convergence Research Division, Korea Institute of Science and Technology, Seoul 136-791, Korea.

ABSTRACT
Alterations of cholesterol metabolism are responsible for vasospastic angina and atherosclerosis. To comprehensively evaluate cholesterol metabolism, 18 sterols, including cholesterol, 6 cholesteryl esters (CEs), 3 cholesterol precursors, and 8 hydroxycholesterols (OHCs), were simultaneously analyzed using hybrid solid-phase extraction (SPE) purification coupled to high-temperature gas chromatography-mass spectrometry (HTGC-MS). Methanol-based hybrid SPE increased the selective extraction, and HTGC resulted in a good chromatographic resolution for the separation of lipophilic compounds. The limits of quantification of cholesterol and CEs ranged from 0.2 to 10.0 μg/ml, while OHCs and cholesterol precursors ranged from 0.01 to 0.10 μg/ml. Linearity as the correlation coefficient was higher than 0.99 with the exception of cholesteryl laurate, myristate, oleate, and linoleate (r² > 0.98). The precision (% coefficient of variation) and accuracy (% bias) ranged from 1.1 to 9.8% and from 75.9 to 125.1%, respectively. The overall recoveries of CEs ranged from 26.1 to 64.0%, and the recoveries of other sterols ranged from 83.8 to 129.3%. The cholesterol signatures showed sex differences in patients with vasospastic angina and may associate with 24-reductases. This technique can be useful for making clinical diagnoses and for an increased understanding of the pathophysiology of vasospastic angina.

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An overview of cholesterol metabolism in humans. Cholesterol biosynthesis is initiated from lanosterol; lanosterol is converted to cholesterol through desmosterol, lathosterol, and 7-dehydrocholesterol as intermediates. 24-Reductase and 7-reductase are enzymes for the production of cholesterol from desmosterol and 7-dehydrocholesterol, respectively. Cholesterol forms CEs with fatty acid by LCAT and ACAT, and it forms OHCs by enzymatic (hydroxylase) or nonenzymatic hydroxylation at the C-4, C-7, C-19, C-20, C-24, C-25, and C-27 positions (see inset).
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fig1: An overview of cholesterol metabolism in humans. Cholesterol biosynthesis is initiated from lanosterol; lanosterol is converted to cholesterol through desmosterol, lathosterol, and 7-dehydrocholesterol as intermediates. 24-Reductase and 7-reductase are enzymes for the production of cholesterol from desmosterol and 7-dehydrocholesterol, respectively. Cholesterol forms CEs with fatty acid by LCAT and ACAT, and it forms OHCs by enzymatic (hydroxylase) or nonenzymatic hydroxylation at the C-4, C-7, C-19, C-20, C-24, C-25, and C-27 positions (see inset).

Mentions: The cholesterol metabolism in tissues and blood can be described as follows. First, acyl-CoA:cholesterol acyltransferase (ACAT) and lecithin:cholesterol acyltransferase (LCAT) are involved in the conversion to cholesteryl esters (CEs) with fatty acids (3, 4). CEs act as a major form of transporter as plasma lipoproteins, or as storage units as lipid droplets (5). Second, cholesterol is converted to hydroxycholesterols (OHCs) by enzymatic (hydroxylase, cytochrome P450 families) or nonenzymatic hydroxylations at various positions (6). OHCs are well-known as regulators of cholesterol homeostasis (7, 8) (Fig. 1).


High-temperature GC-MS-based serum cholesterol signatures may reveal sex differences in vasospastic angina.

Son HH, Moon JY, Seo HS, Kim HH, Chung BC, Choi MH - J. Lipid Res. (2013)

An overview of cholesterol metabolism in humans. Cholesterol biosynthesis is initiated from lanosterol; lanosterol is converted to cholesterol through desmosterol, lathosterol, and 7-dehydrocholesterol as intermediates. 24-Reductase and 7-reductase are enzymes for the production of cholesterol from desmosterol and 7-dehydrocholesterol, respectively. Cholesterol forms CEs with fatty acid by LCAT and ACAT, and it forms OHCs by enzymatic (hydroxylase) or nonenzymatic hydroxylation at the C-4, C-7, C-19, C-20, C-24, C-25, and C-27 positions (see inset).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927468&req=5

fig1: An overview of cholesterol metabolism in humans. Cholesterol biosynthesis is initiated from lanosterol; lanosterol is converted to cholesterol through desmosterol, lathosterol, and 7-dehydrocholesterol as intermediates. 24-Reductase and 7-reductase are enzymes for the production of cholesterol from desmosterol and 7-dehydrocholesterol, respectively. Cholesterol forms CEs with fatty acid by LCAT and ACAT, and it forms OHCs by enzymatic (hydroxylase) or nonenzymatic hydroxylation at the C-4, C-7, C-19, C-20, C-24, C-25, and C-27 positions (see inset).
Mentions: The cholesterol metabolism in tissues and blood can be described as follows. First, acyl-CoA:cholesterol acyltransferase (ACAT) and lecithin:cholesterol acyltransferase (LCAT) are involved in the conversion to cholesteryl esters (CEs) with fatty acids (3, 4). CEs act as a major form of transporter as plasma lipoproteins, or as storage units as lipid droplets (5). Second, cholesterol is converted to hydroxycholesterols (OHCs) by enzymatic (hydroxylase, cytochrome P450 families) or nonenzymatic hydroxylations at various positions (6). OHCs are well-known as regulators of cholesterol homeostasis (7, 8) (Fig. 1).

Bottom Line: Linearity as the correlation coefficient was higher than 0.99 with the exception of cholesteryl laurate, myristate, oleate, and linoleate (r² > 0.98).The precision (% coefficient of variation) and accuracy (% bias) ranged from 1.1 to 9.8% and from 75.9 to 125.1%, respectively.The overall recoveries of CEs ranged from 26.1 to 64.0%, and the recoveries of other sterols ranged from 83.8 to 129.3%.

View Article: PubMed Central - PubMed

Affiliation: Future Convergence Research Division, Korea Institute of Science and Technology, Seoul 136-791, Korea.

ABSTRACT
Alterations of cholesterol metabolism are responsible for vasospastic angina and atherosclerosis. To comprehensively evaluate cholesterol metabolism, 18 sterols, including cholesterol, 6 cholesteryl esters (CEs), 3 cholesterol precursors, and 8 hydroxycholesterols (OHCs), were simultaneously analyzed using hybrid solid-phase extraction (SPE) purification coupled to high-temperature gas chromatography-mass spectrometry (HTGC-MS). Methanol-based hybrid SPE increased the selective extraction, and HTGC resulted in a good chromatographic resolution for the separation of lipophilic compounds. The limits of quantification of cholesterol and CEs ranged from 0.2 to 10.0 μg/ml, while OHCs and cholesterol precursors ranged from 0.01 to 0.10 μg/ml. Linearity as the correlation coefficient was higher than 0.99 with the exception of cholesteryl laurate, myristate, oleate, and linoleate (r² > 0.98). The precision (% coefficient of variation) and accuracy (% bias) ranged from 1.1 to 9.8% and from 75.9 to 125.1%, respectively. The overall recoveries of CEs ranged from 26.1 to 64.0%, and the recoveries of other sterols ranged from 83.8 to 129.3%. The cholesterol signatures showed sex differences in patients with vasospastic angina and may associate with 24-reductases. This technique can be useful for making clinical diagnoses and for an increased understanding of the pathophysiology of vasospastic angina.

Show MeSH
Related in: MedlinePlus