Amino acid–bile acid based molecules: extremely narrow surfactant nanotubes formed by a phenylalanine-substituted cholic acid

2012 ◽  
Vol 48 (98) ◽  
pp. 12011 ◽  
Author(s):  
Leana Travaglini ◽  
Andrea D'Annibale ◽  
Karin Schillén ◽  
Ulf Olsson ◽  
Simona Sennato ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Cholic Acid

scholarly journals The requirement for the amino acid co-germinant duringC. difficilespore germination is influenced by mutations inyabGandcspA

2018 ◽  
Author(s):  
Ritu Shrestha ◽  
Joseph A. Sorg
Keyword(s):  
Amino Acids ◽  
Bile Acid ◽  
Amino Acid ◽  
Clostridium Difficile ◽  
Cholic Acid ◽  
Spore Germination ◽  
Ems Mutagenesis ◽  
Bile Acid Receptor ◽  
Transmission Of Disease ◽  
Cholic Acid Derivatives

AbstractClostridium difficilespore germination is critical for the transmission of disease.C. difficilespores germinate in response to cholic acid derivatives, such as taurocholate (TA), and amino acids, such as glycine or alanine. Although the bile acid germinant receptor is known, the amino acid germinant receptor has remained elusive. Here, we used EMS mutagenesis to generate mutants with altered requirements for the amino acid co-germinant, similar to the strategy used previously to identify the bile acid receptor, CspC. Surprisingly, we identified strains that do not require amino acids as co-germinants, and the mutant spores germinated in response to TA alone. Upon sequencing these mutants, we identified different mutations inyabG.InC. difficile, yabGexpression is required for the processing of CspBA to CspB and CspA and preproSleC to proSleC during spore formation. A definedyabGmutant exacerbated the EMS mutant phenotype. Moreover, we found that various mutations incspAcaused spores to germinate in the presence of TA alone without the requirement of an amino acid. Thus, our study provides evidence that apart from regulating the CspC levels in the spore, CspA is important for recognition of amino acids as co-germinants duringC. difficilespore germination and that two pseudoproteases (CspC and CspA) function as theC. difficilegerminant receptors.

scholarly journals Clostridium scindensATCC 35704: Integration of Nutritional Requirements, the Complete Genome Sequence, and Global Transcriptional Responses to Bile Acids

2019 ◽  
Vol 85 (7) ◽  
Author(s):  
Saravanan Devendran ◽  
Rachana Shrestha ◽  
João M. P. Alves ◽  
Patricia G. Wolf ◽  
Lindsey Ly ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Acid Metabolism ◽  
Deoxycholic Acid ◽  
Nutritional Requirements ◽  
Bile Acid Metabolism ◽  
Content Type ◽  
Secondary Bile Acids

ABSTRACTIn the human gut,Clostridium scindensATCC 35704 is a predominant bacterium and one of the major bile acid 7α-dehydroxylating anaerobes. While this organism is well-studied relative to bile acid metabolism, little is known about the basic nutrition and physiology ofC. scindensATCC 35704. To determine the amino acid and vitamin requirements ofC. scindens, the leave-one-out (one amino acid group or vitamin) technique was used to eliminate the nonessential amino acids and vitamins. With this approach, the amino acid tryptophan and three vitamins (riboflavin, pantothenate, and pyridoxal) were found to be required for the growth ofC. scindens. In the newly developed defined medium,C. scindensfermented glucose mainly to ethanol, acetate, formate, and H2.The genome ofC. scindensATCC 35704 was completed through PacBio sequencing. Pathway analysis of the genome sequence coupled with transcriptome sequencing (RNA-Seq) under defined culture conditions revealed consistency with the growth requirements and end products of glucose metabolism. Induction with bile acids revealed complex and differential responses to cholic acid and deoxycholic acid, including the expression of potentially novel bile acid-inducible genes involved in cholic acid metabolism. Responses to toxic deoxycholic acid included expression of genes predicted to be involved in DNA repair, oxidative stress, cell wall maintenance/metabolism, chaperone synthesis, and downregulation of one-third of the genome. These analyses provide valuable insight into the overall biology ofC. scindenswhich may be important in treatment of disease associated with increased colonic secondary bile acids.IMPORTANCEC. scindensis one of a few identified gut bacterial species capable of converting host cholic acid into disease-associated secondary bile acids such as deoxycholic acid. The current work represents an important advance in understanding the nutritional requirements and response to bile acids of the medically important human gut bacterium,C. scindensATCC 35704. A defined medium has been developed which will further the understanding of bile acid metabolism in the context of growth substrates, cofactors, and other metabolites in the vertebrate gut. Analysis of the complete genome supports the nutritional requirements reported here. Genome-wide transcriptomic analysis of gene expression in the presence of cholic acid and deoxycholic acid provides a unique insight into the complex response ofC. scindensATCC 35704 to primary and secondary bile acids. Also revealed are genes with the potential to function in bile acid transport and metabolism.

Dietary raffinose ameliorates hepatic lipid accumulation induced by cholic acid via modulation of enterohepatic bile acid circulation in rats

2021 ◽  
pp. 1-26
Author(s):  
Kenta Maegawa ◽  
Haruka Koyama ◽  
Satoru Fukiya ◽  
Atsushi Yokota ◽  
Koichiro Ueda ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Bile Acid ◽  
Cholic Acid ◽  
Lipid Accumulation ◽  
Enterohepatic Circulation ◽  
Control Diet ◽  
Hepatic Triglyceride ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract Enterohepatic circulation of 12α-hydroxylated (12αOH) bile acid (BA) is enhanced depending on the energy intake in high-fat diet-fed rats. Such BA metabolism can be reproduced using a diet supplemented with cholic acid (CA), which also induces simple steatosis, without inflammation and fibrosis, accompanied by some other symptoms that are frequently observed in the condition of non-alcoholic fatty liver in rats. We investigated whether supplementation of the diet with raffinose (Raf) improves hepatic lipid accumulation induced by the CA-fed condition in rats. After acclimation to the AIN-93-based control diet, male Wistar rats were fed diets supplemented with a combination of Raf (30 g/kg diet) and/or CA (0.5 g/kg diet) for 4 weeks. Dietary Raf normalised hepatic triglyceride levels (two-way ANOVA P<0.001 for CA, P=0.02 for Raf, and P=0.004 for interaction) in the CA-supplemented diet-fed rats. Dietary Raf supplementation reduced hepatic 12αOH BA concentration (two-way ANOVA P<0.001 for CA, P=0.003 for Raf, and P=0.03 for interaction). The concentration of 12αOH BA was reduced in the aortic and portal plasma. Raf supplementation increased acetic acid concentration in the caecal contents (two-way ANOVA P=0.001 as a main effect). Multiple regression analysis revealed that concentrations of aortic 12αOH BA and caecal acetic acid could serve as predictors of hepatic triglyceride concentration (R2=0.55, P<0.001). However, Raf did not decrease the secondary 12αOH BA concentration in the caecal contents as well as the transaminase activity in the CA diet-fed rats. These results imply that dietary Raf normalises hepatic lipid accumulation via suppression of enterohepatic 12αOH BA circulation.

Overexpression of sterol 12α-hydroxylase (CYP8b1): Effect on rates of cholic acid (CA) synthesis and alteration in bile acid pool composition

2001 ◽  
Vol 120 (5) ◽  
pp. A1
Author(s):  
William M. Pandak ◽  
Phillip B. Hylemon ◽  
Patricia Bohdan ◽  
Ingemar Bjorkhem ◽  
Gosta Eggertsen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Bile Acid Pool ◽  
Acid Pool

Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid

1997 ◽  
Vol 113 (5) ◽  
pp. 1599-1608 ◽  
Author(s):  
RT Stravitz ◽  
AJ Sanyal ◽  
WM Pandak ◽  
ZR Vlahcevic ◽  
JW Beets ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Messenger Rna ◽  
Rat Ileum ◽  
Sodium Dependent ◽  
Bile Acid Transporter ◽  
Acid Transporter

scholarly journals Molecular cloning of two human liver 3 α-hydroxysteroid/dihydrodiol dehydrogenase isoenzymes that are identical with chlordecone reductase and bile-acid binder

1994 ◽  
Vol 299 (2) ◽  
pp. 545-552 ◽  
Author(s):  
Y Deyashiki ◽  
A Ogasawara ◽  
T Nakayama ◽  
M Nakanishi ◽  
Y Miyabe ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Human Liver ◽  
Polyclonal Antibodies ◽  
Amino Acid Sequences ◽  
Cdna Clones ◽  
Amino Acid Residues ◽  
Human Bile ◽  
Coding Regions ◽  
Computer Based

Human liver contains two dihydrodiol dehydrogenases, DD2 and DD4, associated with 3 alpha-hydroxysteroid dehydrogenase activity. We have raised polyclonal antibodies that cross-reacted with the two enzymes and isolated two 1.2 kb cDNA clones (C9 and C11) for the two enzymes from a human liver cDNA library using the antibodies. The clones of C9 and C11 contained coding sequences corresponding to 306 and 321 amino acid residues respectively, but lacked 5′-coding regions around the initiation codon. Sequence analyses of several peptides obtained by enzymic and chemical cleavages of the two purified enzymes verified that the C9 and C11 clones encoded DD2 and DD4 respectively, and further indicated that the sequence of DD2 had at least additional 16 residues upward from the N-terminal sequence deduced from the cDNA. There was 82% amino acid sequence identity between the two enzymes, indicating that the enzymes are genetic isoenzymes. A computer-based comparison of the cDNAs of the isoenzymes with the DNA sequence database revealed that the nucleotide and amino acid sequences of DD2 and DD4 are virtually identical with those of human bile-acid binder and human chlordecone reductase cDNAs respectively.

scholarly journals Cholic acid for primary bile acid synthesis defects: a life-saving therapy allowing a favorable outcome in adulthood

2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Emmanuel Gonzales ◽  
Lorenza Matarazzo ◽  
Stéphanie Franchi-Abella ◽  
Alain Dabadie ◽  
Joseph Cohen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Favorable Outcome ◽  
Life Saving ◽  
Primary Bile Acid

scholarly journals Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Grazia Bossi ◽  
Giuseppe Giordano ◽  
Gaetana Anna Rispoli ◽  
Giuseppe Maggiore ◽  
Mauro Naturale ◽  
...  
Keyword(s):  
Bile Acid ◽  
Replacement Therapy ◽  
Cholic Acid ◽  
Novel Mutation ◽  
Failure To Thrive ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Ionization Mass ◽  
Fast Atom Bombardment Ionization ◽  
Atypical Clinical Presentation

We report definitive diagnosis and effective treatment with oral cholic acid in one Italian male child affected by 3β- hydroxy-Δ5-C27-steroid dehydrogenase (3β- HSD) deficiency. He presented with failure to thrive, hepatomegaly and multiple cystic images in kidneys; no biochemical evidence of cholestasis. Large amounts of bile acid metabolites was detected in urine by fast atom bombardment ionization mass spectrometry (FAB-MS). <em>HSDH3B7</em> gene analysis identified one mutation in intron 4, at nucleotide 432, G&gt;A substitution that has never been reported before.The replacement therapy with oral cholic acid started early after the diagnosis and is still ongoing. Three years later hepatomegaly is no longer evident, liver function is normal and the child is growing regularly. In our experience, clinical features of 3β-HSD deficiency can be very poor and even cholestasis can lack at diagnosis. Early replacement therapy with cholic acid is safe and leads to clinical and biochemical control of the disease.

scholarly journals Structural Basis for Human Norovirus Capsid Binding to Bile Acids

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Turgay Kilic ◽  
Anna Koromyslova ◽  
Grant S. Hansman
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Bile Acids ◽  
Natural Infection ◽  
Structural Basis ◽  
Amino Acid Side Chain ◽  
Blood Group Antigens ◽  
Human Norovirus ◽  
Bile Acid Binding ◽  
P Domain

ABSTRACT A recently developed human norovirus cell culture system revealed that the presence of bile enhanced or was an essential requirement for the growth of certain genotypes. Before this discovery, histo-blood group antigens (HBGAs) were the only well-studied cofactor known for human noroviruses, and there was evidence that several genotypes poorly bound HBGAs. Therefore, the purpose of this study was to investigate how human norovirus capsids interact with bile acids. We found that bile acids had low-micromolar affinities for GII.1, GII.10, and GII.19 capsids but did not bind GI.1, GII.3, GII.4, or GII.17. We showed that bile acid bound at a partially conserved pocket on the norovirus capsid-protruding (P) domain using X-ray crystallography. Amino acid sequence alignment and structural analysis delivered an explanation of selective bile acid binding. Intriguingly, we discovered that binding of the bile acid was the critical step to stabilize several P domain loops that optimally placed an essential amino acid side chain (Asp375) to bind HBGAs in an otherwise HBGA nonbinder (GII.1). Furthermore, bile acid enhanced HBGA binding for a known HBGA binder (GII.10). Altogether, these new data suggest that bile acid functions as a loop-stabilizing regulator and enhancer of HBGA binding for certain norovirus genotypes. IMPORTANCE Given that human norovirus virions likely interact with bile acid during a natural infection, our evidence that an HBGA nonbinder (GII.1) can be converted to an HBGA binder after bile acid binding is of major significance. Our data provide direct evidence that, like HBGAs, bile acid interaction on the capsid is an important cofactor for certain genotypes. However, more unanswered questions seem to arise from these new discoveries. For example, is there an association between the bile acid requirement and the prevalence of certain genotypes? That is, the GII.1 and GII.10 (bile acid binders) genotypes rarely caused outbreaks, whereas the GII.4 and GII.17 genotypes (bile acid nonbinders) were responsible for large epidemics. Therefore, it seems plausible that certain genotypes require bile acids, whereas others have modified their bile acid requirements on the capsid.

Bile Acid Coenzyme A: Amino Acid N‐Acyltransferase in the Amino Acid Conjugation of Bile Acids

2005 ◽  
pp. 374-394 ◽  
Author(s):  
Erin M. Shonsey ◽  
Mindan Sfakianos ◽  
Michelle Johnson ◽  
Dongning He ◽  
Charles N. Falany ◽  
...  
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Bile Acids ◽  
Coenzyme A
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