Mechanisms of steroid oxidation by microorganisms.  XIII.  C<sub>22</sub> acid intermediates in the degradation of the cholesterol side chain

Sih, Charles J.; Wang, Kuang-Chao.; Tai, Hsin‐Hsiung

doi:10.1021/bi00842a038

Cited by 49 publications

(33 citation statements)

References 21 publications

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“…Nocardia was grown on cholesterol radiolabeled at C4 and C26 to help identify partially metabolized cholesterol intermediates (Sih et al, 1968a, Sih et al, 1968b). These studies demonstrated that cholesterol side chain metabolism to C17 keto-sterols proceeds through intermediates in which the side chain has been cleaved at C24 followed by C22 (Figure 1).…”

Section: Elucidation Of Steroid Catabolic Pathways In Bacteriamentioning

confidence: 99%

Pathogen roid rage: Cholesterol utilization byMycobacterium tuberculosis

Wipperman

Sampson

Thomas

2014

Critical Reviews in Biochemistry and Molecular Biology

142

159

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The ability of science and medicine to control the pathogen Mycobacterium tuberculosis (Mtb) requires an understanding of the complex host environment within which it resides. Pathological and biological evidence overwhelmingly demonstrate how the mammalian steroid cholesterol is present throughout the course of infection. Better understanding Mtb requires a more complete understanding of how it utilizes molecules like cholesterol in this environment to sustain the infection of the host. Cholesterol uptake, catabolism, and broader utilization are important for maintenance of the pathogen in the host and it has been experimentally validated to contribute to virulence and pathogenesis. Cholesterol is catabolized by at least three distinct sub-pathways, two for the ring system and one for the side chain, yielding dozens of steroid intermediates with varying biochemical properties. Our ability to control this worldwide infectious agent requires a greater knowledge of how Mtb uses cholesterol to its advantage throughout the course of infection. Herein, the current state of knowledge of cholesterol metabolism by Mtb is reviewed from a biochemical perspective with a focus on the metabolic genes and pathways responsible for cholesterol steroid catabolism.

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Section: Elucidation Of Steroid Catabolic Pathways In Bacteriamentioning

confidence: 99%

Pathogen roid rage: Cholesterol utilization byMycobacterium tuberculosis

Wipperman

Sampson

Thomas

2014

Critical Reviews in Biochemistry and Molecular Biology

142

159

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“…The m/z 157 ion has been assigned previously to the hydroxybenzotropylium ion in the fragmentation of hydroxy A-ring aromatic steroids 37 including methyl esters of steroidal acids. 20 The m/z 145 ion has also been assigned previously, not only in the spectra of 14β(H) C 23 B-ring monoaromatic de-A-steroid hydrocarbons 35 where the ion presumably derives from D-ring fragmentation but also in the spectrum of androst-4,9-diene-17β-ol-3-one, by fragmentation of the B-ring to form a C2-substituted triunsaturated tetrahydroindane-type ion 38 (C 11 H 13 + ). In the mass spectrum of the methyl esters of the partial hydrogenation products of naphthyl-2-ethanoic acid (data not shown), the acid assigned as tetralin-2-ethanoic acid displayed a base peak ion at m/z 145, assigned to a C1-tetralin moiety (C 11 H 13 + ).…”

Section: Articlementioning

confidence: 99%

Steroidal Aromatic ‘Naphthenic Acids’ in Oil Sands Process-Affected Water: Structural Comparisons with Environmental Estrogens

Rowland

West

Jones

et al. 2011

Environ. Sci. Technol.

143

131

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The large volumes, acute toxicity, estrogenicity, and antiandrogenicity of process-affected waters accruing in tailings ponds from the operations of the Alberta oil sands industries pose a significant task for environmental reclamation. Synchronous fluorescence spectra (SFS) suggest that oil sands process-affected water (OSPW) may contain aromatic carboxylic acids, which are among the potentially environmentally important toxicants, but no such acids have yet been identified, limiting interpretations of the results of estrogenicity and other assays. Here we show that multidimensional comprehensive gas chromatography-mass spectrometry (GCxGC-MS) of methyl esters of acids in an OSPW sample produces mass spectra consistent with their assignment as C(19) and C(20) C-ring monoaromatic hydroxy steroid acids, D-ring opened hydroxy and nonhydroxy polyhydrophenanthroic acids with one aromatic and two alicyclic rings and A-ring opened steroidal keto acids. High resolution MS data support the assignment of several of the so-called 'O3' species. When fractions of distilled, esterified, OSPW acid-extractable organics were examined, the putative aromatics were mainly present in a high boiling fraction; when examined by argentation thin layer chromatography, some were present in a fraction with a retardation factor between that of the methyl esters of synthetic monoalicyclic and monoaromatic acids. Ultraviolet absorption spectra of these fractions indicated the presence of benzenoid moieties. SFS of model octahydro- and tetrahydrophenanthroic acids produced emissions at the characteristic excitation wavelengths observed in some OSPW extracts, consistent with the postulations from ultraviolet spectroscopy and mass spectrometry data. We suggest the acids originate from extensive biodegradation of C-ring monoaromatic steroid hydrocarbons and offer a means of differentiating residues at different biodegradation stages in tailings ponds. Structural similarities with estrone and estradiol imply that such compounds may account for some of the environmental estrogenic activity reported in OSPW acid-extractable organics and naphthenic acids.

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“…1. Overview of the pathways involved in sterol degradation in actinobacteria (adapted from Sih et al, 1968b;Fujimoto et al, 1982b;van der Geize et al, 2007). (a) Cholesterol-side-chain degradation is initiated by formation of a cholesterol C26-oic acid (1), involving CYP125 (Rosłoniec et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of ltp3 and ltp4, essential for C24-branched chain sterol-side-chain degradation in Rhodococcus rhodochrous DSM 43269

2012

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A previously identified sterol catabolic gene cluster is widely dispersed among actinobacteria, enabling them to degrade and grow on naturally occurring sterols. We investigated the physiological roles of various genes by targeted inactivation in mutant RG32 of Rhodococcus rhodochrous, which selectively degrades sterol side-chains. The ltp3 and ltp4 deletion mutants were each completely blocked in side-chain degradation of b-sitosterol and campesterol, but not of cholesterol. These results indicated a role for ltp3 and ltp4 in the removal of C24 branches specifically. Bioinformatic analysis of the encoded Ltp3 and Ltp4 proteins revealed relatively high similarity to thiolase enzymes, typically involved in b-oxidation, but the catalytic residues characteristic for thiolase enzymes are not conserved in their amino acid sequences. Removal of the C24-branched side-chain carbons of b-sitosterol was previously shown to proceed via aldolytic cleavage rather than by b-oxidation. Our results therefore suggest that ltp3 and ltp4 probably encode aldol-lyases rather than thiolases. This is the first report, to our knowledge, on the molecular characterization of genes with specific and essential roles in carbon-carbon bond cleavage of C24-branched chain sterols in Rhodococcus strains, most likely acting as aldollyases. The results are a clear contribution to our understanding of sterol degradation in actinobacteria.

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Mechanisms of steroid oxidation by microorganisms. XIII. C₂₂ acid intermediates in the degradation of the cholesterol side chain

Cited by 49 publications

References 21 publications

Pathogen roid rage: Cholesterol utilization byMycobacterium tuberculosis

Pathogen roid rage: Cholesterol utilization byMycobacterium tuberculosis

Steroidal Aromatic ‘Naphthenic Acids’ in Oil Sands Process-Affected Water: Structural Comparisons with Environmental Estrogens

Molecular characterization of ltp3 and ltp4, essential for C24-branched chain sterol-side-chain degradation in Rhodococcus rhodochrous DSM 43269

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Mechanisms of steroid oxidation by microorganisms. XIII. C22 acid intermediates in the degradation of the cholesterol side chain

Cited by 49 publications

References 21 publications

Pathogen roid rage: Cholesterol utilization byMycobacterium tuberculosis

Pathogen roid rage: Cholesterol utilization byMycobacterium tuberculosis

Steroidal Aromatic ‘Naphthenic Acids’ in Oil Sands Process-Affected Water: Structural Comparisons with Environmental Estrogens

Molecular characterization of ltp3 and ltp4, essential for C24-branched chain sterol-side-chain degradation in Rhodococcus rhodochrous DSM 43269

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Mechanisms of steroid oxidation by microorganisms. XIII. C₂₂ acid intermediates in the degradation of the cholesterol side chain