scholarly journals Microbiological degradation of bile acids. Ring a cleavage and 7α,12α-dehydroxylation of cholic acid by Arthrobacter simplex

1969 ◽  
Vol 115 (2) ◽  
pp. 249-256 ◽  
Author(s):  
Shohei Hayakawa ◽  
Yoshiko Kanematsu ◽  
Takashi Fujiwara
Keyword(s):  
Bile Acids ◽  
Cholic Acid ◽  
Valeric Acid ◽  
Hydroxyl Groups ◽  
Partial Synthesis ◽  
Arthrobacter Simplex ◽  
Degradative Pathway ◽  
Acid Degradation

The metabolism of cholic acid by Arthrobacter simplex was investigated. This organism effected both ring a cleavage and elimination of the hydroxyl groups at C-7 and C-12 and gave a new metabolite, (4R)-4-[4α-(2-carboxyethyl)-3aα-hexahydro-7aβ-methyl-5-oxoindan-1β-yl]valeric acid, which was isolated and identified through its partial synthesis. A degradative pathway of cholic acid into this metabolite is tentatively proposed, and the possibility that the proposed pathway could be extended to the cholic acid degradation by other microorganisms besides A. simplex is discussed. The possibility that the observed reactions in vitro could occur during the metabolism of bile acids in vivo is considered.

scholarly journals Microbiological degradation of bile acids. The preparation of some hypothetical metabolites involved in cholic acid degradation

1976 ◽  
Vol 154 (3) ◽  
pp. 577-587 ◽  
Author(s):  
S Hayakawa ◽  
Y Kanematsu ◽  
T Fujiwara ◽  
H Kako
Keyword(s):  
Fatty Acid ◽  
Carboxylic Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Valeric Acid ◽  
Side Chain ◽  
Partial Synthesis ◽  
Arthrobacter Simplex ◽  
Acid Degradation ◽  
Oxidation Mechanisms

1. To identify the intermediates involved in the degradation of cholic acid, the further degradation of (4R)-4-[4a-(2-carboxyethyl)-3aa-hexahydro-7ab-methyl-5-oxoindan-1β-yl]valeric acid (IVa) by Arthrobacter simplex was attempted. The organism could not utilize this acid but some hypothetical intermediate metabolities of compound (IVa) were prepared for later use as reference compounds. 2. The nor homologue (IIIa) and the dinor homologue (IIIb) of compound (IVa) were prepared by exposure of 3-oxo-24-nor-5β-cholan-23-oic acid (I) and (20S)-3b-hydroxy-5-pregnene-20-carboxylic acid (II) to A. simplex respectively. These compounds correspond to the respective metabolites produced by the shortening of the valeric acid side chain of compound (IVa) in a manner analogous to the conventional fatty acid a- and b-oxidation mechanisms. Their structures were confirmed by partial synthesis. 3. The following authentic samples of reduction products of the oxodicarboxylic acids (IIIa), (IIIb) and (IVa) were also synthesized as hypothetical metabolities: (4R)-4-[3aa-hexahydro-5a-hydroxy-4a-(3-hydroxypropyl)-7ab-methylindan-1b-yl]valeric acid (Vb) and its nor homologue (VIIa) and dinor homologue (IXa);(4R)-4-[3Aaa-hexahydro-5a-hydroxy-4a-(3-hydroxypropyl)-7ab-methylindan-1b-yl]-pentan-1-ol (Vc); and their respective 5β epimers (Ve), (VIIc), (IXc) and (Vf). 4. In connexion with the non-utilization of compound (IVa) by A. simplex, the possibility that not all the metabolites formed from cholic acid by a certain micro-organism can be utilized by the same organism is considered.

scholarly journals Microbiological degradation of bile acids. Nitrogenous hexahydroindane derivatives formed from cholic acid by Streptomyces rubescens

1976 ◽  
Vol 160 (3) ◽  
pp. 745-755 ◽  
Author(s):  
S Hayakawa ◽  
S Hashimoto ◽  
T Onaka
Keyword(s):  
Cholic Acid ◽  
Bond Formation ◽  
Valeric Acid ◽  
Amide Bond ◽  
Side Chain ◽  
Mechanism Of Formation ◽  
Partial Synthesis ◽  
Degradative Pathway ◽  
Amide Bond Formation ◽  
New Compounds

The metabolism of cholic acid (I) by Streptomyces rubescens was investigated. This organism effected ring A cleavage, side-chain shortening and amide bond formation and gave the following metabolites: (4R)-4-[4α-(2-carboxyethyl)-3aα-hexahydro-7aβ-methyl-5-oxoindan-1 β-yl]valeric acid (IIa) and its mono-amide (valeramide) (IIb); and 2,3,4,6, 6aβ,7,8,9,9aα,9bβ-decahydro-6aβ-methyl-1H-cyclopenta[f]quinoline-3,7-dione(IIIe)and its homologues with the β-oriented side chains, valeric acid, valeramide, butanone and propionic acid, in the place of the oxo group at C-7, i.e.compounds (IIIa), (IIIb), (IIIc) and (IIId) respectively. All the nitrogenous metabolites were new compounds, and their structures were established by partial synthesis except for the metabolite (IIIc). The mechanism of formation of these metabolites is considered. A degradative pathway of cholic acid (I) into the metabolites is also tentatively proposed.

Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake

2003 ◽  
Vol 285 (5) ◽  
pp. G829-G839 ◽  
Author(s):  
Soichiro Hata ◽  
Pijun Wang ◽  
Nicole Eftychiou ◽  
Meenakshisundaram Ananthanarayanan ◽  
Ashok Batta ◽  
...  
Keyword(s):  
Bile Acids ◽  
Competitive Inhibition ◽  
Organic Anion ◽  
Inducible Promoter ◽  
Hydroxyl Groups ◽  
Organic Anion Transporting Polypeptide ◽  
Hela Cell Lines ◽  
Dependent Transport

Transport of a series of3H-radiolabeled C23, C24, and C27bile acid derivatives was compared and contrasted in HeLa cell lines stably transfected with rat Na+/taurocholate cotransporting polypeptide (ntcp) or organic anion transporting polypeptide 1 (oatp1) in which expression was under regulation of a zinc-inducible promoter. Similar uptake patterns were observed for both ntcp and oatp1, except that unconjugated hyodeoxycholate was a substrate of oatp1 but not ntcp. Conjugated bile acids were transported better than nonconjugated bile acids, and the configuration of the hydroxyl groups (α or β) had little influence on uptake. Although cholic and 23 norcholic acids were transported by ntcp and oatp1, other unconjugated bile acids (chenodeoxycholic, ursodeoxycholic) were not. In contrast to ntcp, oatp1-mediated uptake of the trihydroxy bile acids taurocholate and glycocholate was four- to eightfold below that of the corresponding dihydroxy conjugates. Ntcp mediated high affinity, sodium-dependent transport of [35S]sulfobromophthalein with a Kmsimilar to that of oatp1-mediated transport of [35S]sulfobromophthalein ( Km= 3.7 vs. 3.3 μM, respectively). In addition, for both transporters, uptake of sulfobromophthalein and taurocholic acid showed mutual competitive inhibition. These results indicate that the substrate specificity of ntcp is considerably broader than previously suspected and caution the extrapolation of transport data obtained in vitro to physiological function in vivo.

scholarly journals Osseointegrating and phase-oriented micro-arc-oxidized titanium dioxide bone implants

2021 ◽  
Vol 19 ◽  
pp. 228080002110068
Author(s):  
Hsien-Te Chen ◽  
Hsin-I Lin ◽  
Chi-Jen Chung ◽  
Chih-Hsin Tang ◽  
Ju-Liang He
Keyword(s):  
Titanium Dioxide ◽  
High Surface ◽  
Cell Activity ◽  
Active Surface ◽  
Rutile Phase ◽  
Hydroxyl Groups ◽  
Bone Implant ◽  
Implant System

Here, we present a bone implant system of phase-oriented titanium dioxide (TiO2) fabricated by the micro-arc oxidation method (MAO) on β-Ti to facilitate improved osseointegration. This (101) rutile-phase-dominant MAO TiO2 (R-TiO2) is biocompatible due to its high surface roughness, bone-mimetic structure, and preferential crystalline orientation. Furthermore, (101) R-TiO2 possesses active and abundant hydroxyl groups that play a significant role in enhancing hydroxyapatite formation and cell adhesion and promote cell activity leading to osseointegration. The implants had been elicited their favorable cellular behavior in vitro in the previous publications; in addition, they exhibit excellent shear strength and promote bone–implant contact, osteogenesis, and tissue formation in vivo. Hence, it can be concluded that this MAO R-TiO2 bone implant system provides a favorable active surface for efficient osseointegration and is suitable for clinical applications.

scholarly journals Microbiological degradation of bile acids. The preparation of hexahydroindane derivatives as substrates for studying cholic acid degradation

1977 ◽  
Vol 164 (3) ◽  
pp. 709-714 ◽  
Author(s):  
S Hayakawa ◽  
T Takata ◽  
T Fujiwara ◽  
S Hashimoto
Keyword(s):  
Carboxylic Acid ◽  
Cholic Acid ◽  
Propionic Acid ◽  
Good Yield ◽  
Degradation Products ◽  
Chemical Oxidation ◽  
Compound Iiib ◽  
Partial Synthesis ◽  
Arthrobacter Simplex ◽  
Simple Method

Relatively large amounts of 3-(3aalpha-hexahydro-7abeta-methyl-1,5-dioxoindan-4alpha-yl)propionic acid (IIb), which is believed to be one of the intermediates involved in the degradation of cholic acid (I), were needed to identify is further degradation products. A simple method for the preparation of this compound was then investigated. Arthrobacter simplex could degrade-3-oxoandrost-4-ene-17beta-carboxylic acid (IIIa) to 3-(1beta-carboxy-3aalpha-hexahydro-7abeta-methyl-5-oxoindan-4alpha-yl)propionic acid (IVa) in good yield, the structure of which was established by partial synthesis. It was therefore expected that, if a similar degradation by this organism occurred with 17alpha-hydroxy-3-oxoandrost-4-ene-17beta-carboxylic acid (IIIb), which is easily obtained by chemical oxidation of commercially availabe 17alpha-hydroxydeoxycorticosterone, the resulting product, 3-(1beta-carboxy-3aalpha-hexahydro-1alpha-hydroxy-7abeta-methyl-5-oxoindan-4alpha-yl)propionic acid (IVb), could be readily converted chemically into the required dioxocarboxylic acid, (IIb). Exposure of compound (IIIb) to A. simplex produced, as expected, compound (IVb) which was then oxidized with NaBiO3 to give a reasonable yield of compound (IIb).

Comparative hepatotoxicity of cholic acid, deoxycholic acid and lithocholic acid in the rat: in vivo and in vitro studies

1992 ◽  
Vol 61 (2-3) ◽  
pp. 291-304 ◽  
Author(s):  
N.M. Delzenne ◽  
P.Buc Calderon ◽  
H.S. Taper ◽  
M.B. Roberfroid
Keyword(s):  
Cholic Acid ◽  
Deoxycholic Acid ◽  
Lithocholic Acid ◽  
In Vitro Studies

scholarly journals Anticoagulant Properties of a Green Algal Rhamnan-type Sulfated Polysaccharide and Its Low-molecular-weight Fragments Prepared by Mild Acid Degradation

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 445 ◽  
Author(s):  
Xue Liu ◽  
Peng Du ◽  
Xiao Liu ◽  
Sujian Cao ◽  
Ling Qin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Anticoagulant Activity ◽  
Sulfated Polysaccharide ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Acid Degradation ◽  
Molecular Weights ◽  
Green Algal

The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of MSP and MSP-F1–MSP-F6 were 335 kDa, 240 kDa, 90 kDa, 40 kDa, 24 kDa, 12 kDa, and 6.8 kDa, respectively. The polysaccharides were sulfated rhamnans that consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ units with partial sulfation at C-2 of →3)-α-l-Rhap-(1→ and C-3 of →2)-α-l-Rhap-(1→. Anticoagulant properties in vitro of MSP and MSP-F1–MSP-F6 were evaluated by studying the activated partial thromboplastin time, thrombin time, and prothrombin time. Anticoagulant activities in vivo of MSP and MSP-F4 were further evaluated; their fibrin(ogen)olytic activities in vivo and thrombolytic properties in vitro were also assessed by D-dimer, fibrin degradation products, plasminogen activator inhibitior-1, and clot lytic rate assays. The results showed that MSP and MSP-F1–MSP-F4 with molecular weights of 24–240 kDa had strong anticoagulant activities. A decrease in the molecular weight of MSP-Fs was accompanied by a decrease in the anticoagulant activity, and higher anticoagulant activity requires a molecular weight of over 12 kDa. MSP and MSP-F4 possessed strong anticoagulant activities in vivo, as well as high fibrin(ogen)olytic and thrombolytic activities. MSP and MSP-F4 have potential as drug or helpful food supplements for human health.

scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

Polyphenols in Food: Cancer Prevention and Apoptosis Induction

2018 ◽  
Vol 25 (36) ◽  
pp. 4740-4757 ◽  
Author(s):  
Ashita Sharma ◽  
Mandeep Kaur ◽  
Jatinder Kaur Katnoria ◽  
Avinash Kaur Nagpal
Keyword(s):  
Cancer Prevention ◽  
Defense Mechanism ◽  
Antioxidant Property ◽  
The Body ◽  
Water Soluble ◽  
Stress Factors ◽  
In Vivo Studies ◽  
Hydroxyl Groups

Polyphenols are a group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed.

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