Hydrophobicity and self‐association (micellization) of bile salts with a lactone or lactam group in a steroid skeleton

2020 ◽  
Author(s):  
Mihalj Poša ◽  
Vesna Tepavčević ◽  
Ljubica Grbović ◽  
Mira Mikulić ◽  
Ksenija Pavlović
Keyword(s):  
Bile Salts ◽  
Self Association ◽  
Steroid Skeleton

scholarly journals Investigations on the Degradation of the Bile Salt Cholate via the 9,10-Seco-Pathway Reveals the Formation of a Novel Recalcitrant Steroid Compound by a Side Reaction in Sphingobium sp. Strain Chol11

2021 ◽  
Vol 9 (10) ◽  
pp. 2146
Author(s):  
Franziska Maria Feller ◽  
Sebastian Eilebrecht ◽  
Ruslan Nedielkov ◽  
Onur Yücel ◽  
Julia Alvincz ◽  
...  
Keyword(s):  
Bile Salts ◽  
Agricultural Soils ◽  
Pseudomonas Stutzeri ◽  
Side Reaction ◽  
Transcriptome Profiling ◽  
Ring Closure ◽  
Soil Slurry ◽  
Unknown Compound ◽  
Hormone Responses ◽  
Steroid Skeleton

Bile salts such as cholate are steroid compounds from the digestive tracts of vertebrates, which enter the environment upon excretion, e.g., in manure. Environmental bacteria degrade bile salts aerobically via two pathway variants involving intermediates with Δ1,4- or Δ4,6-3-keto-structures of the steroid skeleton. Recent studies indicated that degradation of bile salts via Δ4,6-3-keto intermediates in Sphingobium sp. strain Chol11 proceeds via 9,10-seco cleavage of the steroid skeleton. For further elucidation, the presumptive product of this cleavage, 3,12β-dihydroxy-9,10-seco-androsta-1,3,5(10),6-tetraene-9,17-dione (DHSATD), was provided to strain Chol11 in a co-culture approach with Pseudomonas stutzeri Chol1 and as purified substrate. Strain Chol11 converted DHSATD to the so far unknown compound 4-methyl-3-deoxy-1,9,12-trihydroxyestra-1,3,5(10)7-tetraene-6,17-dione (MDTETD), presumably in a side reaction involving an unusual ring closure. MDTETD was neither degraded by strains Chol1 and Chol11 nor in enrichment cultures. Functional transcriptome profiling of zebrafish embryos after exposure to MDTETD identified a significant overrepresentation of genes linked to hormone responses. In both pathway variants, steroid degradation intermediates transiently accumulate in supernatants of laboratory cultures. Soil slurry experiments indicated that bacteria using both pathway variants were active and also released their respective intermediates into the environment. This instance could enable the formation of recalcitrant steroid metabolites by interspecies cross-feeding in agricultural soils.

scholarly journals Self-association of unconjugated bilirubin-IX α in aqueous solution at pH 10.0 and physical-chemical interactions with bile salt monomers and micelles

1979 ◽  
Vol 179 (3) ◽  
pp. 675-689 ◽  
Author(s):  
M C Carey ◽  
A P Koretsky
Keyword(s):  
Aqueous Solution ◽  
Absorption Spectrum ◽  
Bile Salt ◽  
Bile Salts ◽  
Sodium Dodecyl ◽  
Chemical Properties ◽  
Critical Micellar Concentration ◽  
Solvent Mixtures ◽  
Physical Chemical ◽  
Self Association

Spectrophotometric measurements of bilirubin-IX alpha in water and in aqueous/organic solvent mixtures at pH 10.0 as a function of bilirubin-IX alpha concentration (approx. 0.6–400 microM) are consistent with the formation of dimers (KD - 1.5 microM) in dilute (less than 10 microM) aqueous solution and further self-aggregation to multimers at higher concentrations. Added urea (to 10M) and increases in temperature (to 62 degrees C) obliterate the dimer-multimer transition at 10 microM, but added NaCl (to 0.30 M) promotes strong aggregation of dimers over a narrow concentration range, suggesting a ‘micellization’ phenomenon. Concentrations of dioxan or ethanol greater than 60% (v/v) in water were required to obtain the absorption spectrum of bilirubin-IX alpha monomers, suggesting that both hydrophobic and electrostatic (pi-orbital) interactions are involved in stabilizing the dimeric state in water. Micellar concentrations of sodium dodecyl sulphate induced spectrophotometric shifts in the dimer absorption spectrum of bilirubin-IX alpha consistent with progressive partitioning of bilirubin-IX alpha monomers into a relatively non-polar region of the micelles and allowed a deduction of the apparent critical micellar concentration that closely approximated the literature values. The pattern of bilirubin IX alpha association with bile salts is complex, since the absorption spectrum shifts hypsochromically below and bathochromically above the critical micellar concentration of the bile salts. Consistent with these observations, bilirubin IX alpha appears to bind to the polar face of bile salt monomers and to the polar perimeter of small bile salt micelles. At higher bile salt concentrations some-bilirubin-IX alpha monomers partition into the hydrophobic interior of the bile salt micelles. Our results suggest that under physiological conditions the natural conjugates of bilirubin-IX alpha may exhibit similar physical chemical properties in bile, in that dimers, highly aggregated multimers and bile salt-associated monomers may co-exist.

scholarly journals Proteome, bioinformatic and functional analyses reveal a distinct and conserved metabolic pathway for bile salt degradation in the Sphingomonadaceae

2021 ◽  
Author(s):  
Franziska Maria Feller ◽  
Lars Wöhlbrand ◽  
Johannes Holert ◽  
Vanessa Schnaars ◽  
Lea Elsner ◽  
...  
Keyword(s):  
Bile Salt ◽  
Gene Cluster ◽  
Metabolic Pathway ◽  
Bile Salts ◽  
Model Organisms ◽  
Side Chain ◽  
Putative Gene ◽  
Degrading Bacteria ◽  
Functional Analyses ◽  
Steroid Skeleton

Bile salts are amphiphilic steroids with a C5 carboxylic side chain with digestive functions in vertebrates. Upon excretion, they are degraded by environmental bacteria. Degradation of the bile-salt steroid skeleton resembles the well-studied pathway for other steroids like testosterone, while specific differences occur during side-chain degradation and the initiating transformations of the steroid skeleton. Of the latter, two variants via either Δ1,4- or Δ4,6-3-ketostructures of the steroid skeleton exist for 7-hydroxy bile salts. While the Δ1,4- variant is well-known from many model organisms, the Δ4,6-variant involving a 7-hydroxysteroid dehydratase as key enzyme has not been systematically studied. Here, combined proteomic, bioinformatic and functional analyses of the Δ4,6-variant in Sphingobium sp. strain Chol11 were performed. They revealed a degradation of the steroid rings similar to the Δ1,4-variant except for the elimination of the 7-OH as key difference. In contrast, differential production of the respective proteins revealed a putative gene cluster for side-chain degradation encoding a CoA-ligase, an acyl-CoA dehydrogenase, a Rieske monooxygenase, and an amidase, but lacking most canonical genes known from other steroid-degrading bacteria. Bioinformatic analyses predicted the Δ4,6-variant to be widespread among the Sphingomonadaceae, which was verified for three type strains which also have the predicted side-chain degradation cluster. A second amidase in the side-chain degradation gene cluster of strain Chol11 was shown to cleave conjugated bile salts while having low similarity to known bile-salt hydrolases. This study signifies members of the Sphingomonadaceae remarkably well-adapted to the utilization of bile salts via a partially distinct metabolic pathway.

scholarly journals Proteome, bioinformatic and functional analyses reveal a distinct and conserved metabolic pathway for bile salt degradation in the Sphingomonadaceae

2021 ◽  
Author(s):  
Franziska M. Feller ◽  
Lars Wöhlbrand ◽  
Johannes Holert ◽  
Vanessa Schnaars ◽  
Lea Elsner ◽  
...  
Keyword(s):  
Bile Salt ◽  
Gene Cluster ◽  
Metabolic Pathway ◽  
Bile Salts ◽  
Side Chain ◽  
Putative Gene ◽  
Degrading Bacteria ◽  
Environmental Bacteria ◽  
Functional Analyses ◽  
Steroid Skeleton

Bile salts are amphiphilic steroids chain with digestive functions in vertebrates. Upon excretion, bile salts are degraded by environmental bacteria. Degradation of the bile-salt steroid skeleton resembles the well-studied pathway for other steroids like testosterone, while specific differences occur during side-chain degradation and the initiating transformations of the steroid skeleton. Of the latter, two variants via either Δ 1,4 - or Δ 4,6 -3-ketostructures of the steroid skeleton exist for 7-hydroxy bile salts. While the Δ 1,4 - variant is well-known from many model organisms, the Δ 4,6 -variant involving a 7-hydroxysteroid dehydratase as key enzyme has not been systematically studied. Here, combined proteomic, bioinformatic and functional analyses of the Δ 4,6 -variant in Sphingobium sp. strain Chol11 were performed. They revealed a degradation of the steroid rings similar to the Δ 1,4 -variant except for the elimination of the 7-OH as a key difference. In contrast, differential production of the respective proteins revealed a putative gene cluster degradation of the C 5 carboxylic side chain encoding a CoA-ligase, an acyl-CoA dehydrogenase, a Rieske monooxygenase, and an amidase, but lacking most canonical genes known from other steroid-degrading bacteria. Bioinformatic analyses predicted the Δ 4,6 -variant to be widespread among the Sphingomonadaceae , which was verified for three type strains which also have the predicted side-chain degradation cluster. A second amidase in the side-chain degradation gene cluster of strain Chol11 was shown to cleave conjugated bile salts while having low similarity to known bile-salt hydrolases. This study signifies members of the Sphingomonadaceae remarkably well-adapted to the utilization of bile salts via a partially distinct metabolic pathway. Importance This study highlights the biochemical diversity of bacterial degradation of steroid compounds, in particular bile salts. Furthermore, it substantiates and advances knowledge of a variant pathway for degradation of steroids by sphingomonads, a group of environmental bacteria that are well-known for their broad metabolic capabilities. Biodegradation of bile salts is a critical process due to the high input of these compounds from manure into agricultural soils and wastewater treatment plants. In addition, these results may also be relevant for the biotechnological production of bile salts or other steroid compounds with pharmaceutical functions.

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