Identification of bile alcohols in human bile.

Kuroki, Shin-Ichiro; Shimazu, Kazuhiro; Kuwabara, Miho; Une, Mizuho; Kihira, Kenji; Kuramoto, Taiju; Hoshita, Takahiko

doi:10.1016/s0022-2275(20)34393-5

Cited by 38 publications

(5 citation statements)

References 34 publications

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“…One additional metabolite had a mass spectrum showing peaks at m/z 618, m/z 528, m/z 438, m/z 343, m/z 281, and m/z 253 (Figure 5C), corresponding to a C26 bile alcohol with two hydroxyl groups or one hydroxyl group and one double bond in the steroid side chain. An almost identical mass spectrum has been published for 27-nor-5β-cholest-25-ene-3R,7R,12R, 24-tetrol (Figure 3) (30). Finally, trace amounts of 5β-cholestane-3R,7R,12R,25-tetrol (Figure 3) were observed, as shown from the characteristic base peak at m/z 131 in the mass spectrum of the trimethylsilyl derivative and ions at m/z 544 (M -90), 454 m/z (M -2 × 90), m/z 343, and m/z 253 (31).…”

Section: Resultssupporting

confidence: 59%

Putative Helix F Contributes to Regioselectivity of Hydroxylation in Mitochondrial Cytochrome P450 27A1

2001

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On the basis of alignment with structurally characterized cytochromes P450 (P450s), we have identified the putative F and G helices of mitochondrial P450s 27A1 and 11A. We introduced substitutions at Phe-207, Ile-211, and Phe-215 within putative helix F and at Trp-235 and Tyr-238 within putative helix G in P450 27A1 and compared wild type and mutants with respect to catalytic activity, product pattern, substrate binding, formation of hydrogen peroxide, and interaction with redox partner. Results indicate that the mutated residues are important for delivery of the correctly oriented substrate to the P450 active site. The I211K and F215K mutations, for example, affected the regioselectivity of P450 27A1-dependent hydroxylation reactions and conferred the P450 capacity to cleave the C-C bond of the substrate during the catalytic cycle. Studies of P450 11A1 indicate that Phe-202 has functions similar to those of its counterpart in P450 27A1 (Phe-215). We propose that putative helices F and G form the sides of the substrate-access channel, thus providing the additional mechanism to control regioselectivity of hydroxylation in mitochondrial P450s.

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Section: Resultssupporting

confidence: 59%

Putative Helix F Contributes to Regioselectivity of Hydroxylation in Mitochondrial Cytochrome P450 27A1

2001

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“…At the present time the biosynthetic route of the C 26 -24,25-pentol is postulated as shown in Fig. 1 (3,9). Thus, the biosynthetic route is thought to be identical with that of cholic acid ( VII ), the most common bile acid in mammals, up to the intermediate 3 ␣ ,7 ␣ ,12 ␣ -trihydroxy-24-oxo-5 ␤ -cholestanoyl-CoA ( VI ).…”

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confidence: 92%

Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol, in human urine

Une¹,

Takenaka²,

Kuramoto³

et al. 2000

Journal of Lipid Research

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The stereochemistry at C-24 and C-25 of 27-nor-5 ␤ -cholestane-3 ␣ ,7 ␣ ,12 ␣ ,24,25-pentol, a principal bile alcohol in human urine, and its biosynthesis are studied. Four stereoisomers of the C 26 -24,25-pentols were synthesized by reduction with LiAlH 4 of the corresponding epoxides prepared from (24 S )-or (24 R )-27-nor-5 ␤ -cholest-25-ene-3 ␣ , 7 ␣ ,12 ␣ ,24-tetrol. The stereochemistries at C-25 were deduced by comparison of the C 26 -24,25-pentols with the oxidation products of (24 Z )-27-nor-5 ␤ -cholest-24-ene-3 ␣ ,7 ␣ ,12 ␣triol with osmium tetraoxide. On the basis of this assignment, the principal bile alcohol excreted into human and rat urine was determined to be (24 S ,25 R )-27-nor-5 ␤ -cholestane-3 ␣ ,7 ␣ ,12 ␣ ,24,25-pentol, accompanied by a lesser amount of (24 R ,25 R )-isomer. To elucidate the biosynthesis of the C 26 -24,25-pentol, a putative intermediate, 3 ␣ ,7 ␣ ,12 ␣trihydroxy-27-nor-5 ␤ -cholestan-24-one, derived from 3 ␣ ,7 ␣ , 12 ␣ -trihydroxy-24-oxo-5 ␤ -cholestanoic acid by decarboxylation during the side-chain oxidation of 3 ␣ ,7 ␣ ,12 ␣ -trihydroxy-5 ␤ -cholestanoic acid, was incubated with rat liver homogenates. The 24-oxo-bile alcohol could be efficiently reduced to yield mainly (24 R )-27-nor-5 ␤ -cholestane-3 ␣ ,7 ␣ ,12 ␣ ,24tetrol. If a 25R-hydroxylation of the latter steroid occurs, it should lead to formation of (24 S ,25 R )-C 26 -24,25-pentol. Now it has appeared that a major bile alcohol excreted into human urine is (24

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“…There are few reports of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol as the aglycone or the glucuronide in the literature. 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide is the major bile alcohol found in human urine [ 3 , 4 , 5 , 6 , 7 ]. The presence of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol in urine has been associated with liver disease [ 3 , 4 , 5 , 6 , 7 , 8 ] and disorders of lipid [ 9 ] storage.…”

Section: Introductionmentioning

confidence: 99%

“…27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide is the major bile alcohol found in human urine [ 3 , 4 , 5 , 6 , 7 ]. The presence of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol in urine has been associated with liver disease [ 3 , 4 , 5 , 6 , 7 , 8 ] and disorders of lipid [ 9 ] storage. Recently, 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide, detected by LC/MS, was reported as a potential biomarker in serum for epithelium ovarian cancer by Wu and coworkers [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation and Identification of a Urinary Biomarker for Lung Cancer: 27-Nor-5β-Cholestane-3α,7α,12α,24R,25S Pentol Glucuronide and Its Deuterated Analog

Blackman,

Raju,

Mushti

et al. 2024

Molecules

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An untargeted metabolomic study identified four potential lung cancer diagnostic biomarkers in human urine. One of the potential biomarkers was an unidentified feature possessing a m/z value of 561+. “561+” was isolated from human urine and tentatively identified as 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol glucuronide with unknown C24,25 stereochemistry using 1H NMR and mass spectrometry. In a prior report, the C24,25 stereochemistry of the aglycone, 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol, was found to be 24S,25R through GC analysis of the acetonide-TMS derivative. An authentic sample was prepared and found not to have the same stereochemistry as ”561+”. To identify the C24,25 stereochemistry, four C24,C25 diastereoisomeric alcohols of 27-nor-5β-cholestane-3α,7α,12α,24,25 pentol were prepared from chiral amino acids. Using an LCMS method, the C24,C25 stereochemistry of the “561+” aglycone was determined to be 24R,25S. With the correct aglycone in hand, it was coupled with glucuronic acid to complete the first reported synthesis of 27-nor-5β-cholestane-3α,7α,12α,24R,25S pentol glucuronide. Deuterium labeled 27-nor-5β-cholestane-3α,7α,12α,24R,25S pentol was also synthesized for use as an internal standard for MS quantitation.

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Identification of bile alcohols in human bile.

Cited by 38 publications

References 34 publications

Putative Helix F Contributes to Regioselectivity of Hydroxylation in Mitochondrial Cytochrome P450 27A1

Putative Helix F Contributes to Regioselectivity of Hydroxylation in Mitochondrial Cytochrome P450 27A1

Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5β-cholestane-3α,7α,12α,24,25-pentol, in human urine

Isolation and Identification of a Urinary Biomarker for Lung Cancer: 27-Nor-5β-Cholestane-3α,7α,12α,24R,25S Pentol Glucuronide and Its Deuterated Analog

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