scholarly journals Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway

2008 ◽  
Vol 417 (1) ◽  
pp. 43-58 ◽  
Author(s):  
Robert D. Finn ◽  
Colin J. Henderson ◽  
Claire L. Scott ◽  
C. Roland Wolf

The liver is responsible for key metabolic functions, including control of normal homoeostasis in response to diet and xenobiotic metabolism/detoxification. We have shown previously that inactivation of the hepatic cytochrome P450 system through conditional deletion of POR (P450 oxidoreductase) induces hepatic steatosis, liver growth and P450 expression. We have exploited a new conditional model of POR deletion to investigate the mechanism underlying these changes. We demonstrate that P450 induction, liver growth and hepatic triacylglycerol (triglyceride) homoeostasis are intimately linked and provide evidence that the observed phenotypes result from hepatic accumulation of unsaturated fatty acids, which mediate these phenotypes by activation of the nuclear receptor CAR (constitutive androstane receptor) and, to a lesser degree, PXR (pregnane X receptor). To our knowledge this is the first direct evidence that P450s play a major role in controlling unsaturated fatty acid homoeostasis via CAR. The regulation of P450s involved in xenobiotic metabolism by this mechanism has potentially significant implications for individual responses to drugs and environmental chemicals.

2019 ◽  
Vol 57 (6) ◽  
pp. 665 ◽  
Author(s):  
Yen Thi Hoang ◽  
Quynh Thi Thu Tran ◽  
Ha Hoang Chu ◽  
Tuyen Thi Do ◽  
Thanh Tat Dang ◽  
...  

Purple nonsulfur bacteria are a group that has so much biotechnological applications, particularly in producing of functional food rich with unsaturated fatty acids. A purple nonsulfur bacterium (named HPB.6) was chosen based on its strong growth, high lipid and synthesis of unsaturated fatty acid (omega 6,7,9). Studying on basic biological characteristics showed that the cells of HPB.6 were observed as ovoid-rod shape, none motility, Gram negative staining. The diameter of single bacterium was about 0.8-1.0 µm. The cells divide by binary fission and had bacteriochlorophyll a (Bchl a). This bacterium grew well on medium with carbon and nitrogen sources such as acetate, succinate, pyruvate, butyrate, glutamate, arginine, leucine, tyrosine, alanine, methionine, threonine, glutamine, yeast extract and NH4Cl. This selected strain grew well on medium with salt concentrations from 1.5 - 6.0% (optimum 3%), pH from 5.0 to 8.0 (optimum at pH 6.5) and could withstand Na2S at 4.0 - 5.2 mM. Based on morphological, physiological properties and 16S rRNA analysis received demonstrated that HPB.6 strain belongs to the species Rhodovulum sulfidophilum.


1977 ◽  
Vol 23 (9) ◽  
pp. 1145-1150 ◽  
Author(s):  
Robert A. Altenbern

Cells of Staphylococcus aureus, strain S-6, can grow in the presence of 100 μg of cerulenin/ml if the basal medium is supplemented with certain saturated or unsaturated fatty acids. The production of enterotoxin B (SEB) is markedly influenced by both the ratio of saturated to unsaturated fatty acid and by the melting point of the unsaturated fatty acid supplement. The results presented suggest that a certain degree of membrane fluidity promotes maximum SEB production and that greater or lesser degrees of membrane fluidity prohibit substantial SEB formation but fail to affect final growth density.


2009 ◽  
Vol 192 (1) ◽  
pp. 280-285 ◽  
Author(s):  
Chitra Subramanian ◽  
Charles O. Rock ◽  
Yong-Mei Zhang

ABSTRACT The fabA and fabB genes are responsible for anaerobic unsaturated fatty acid formation in Pseudomonas aeruginosa. Expression of the fabAB operon was repressed by exogenous unsaturated fatty acids, and DNA sequences upstream of the translational start site were used to affinity purify DesT. The single protein interaction with the fabAB promoter detected in wild-type cell extracts was absent in the desT deletion strain, as was the repression of fabAB expression by unsaturated fatty acids. Thus, DesT senses the overall composition of the acyl-coenzyme A pool to coordinate the expression of the operons for the anaerobic (fabAB) and aerobic (desCB) pathways for unsaturated fatty acid synthesis.


2021 ◽  
Vol 81 (4) ◽  
pp. 1106-1114
Author(s):  
İ. Emre

Abstract Medicinal plants have a significant role in preventing and curing several diseases, and Tanacetum L. is one of these plants. The aim of the present study is to determine the fatty acid, lipid-soluble vitamin, sterol, phenolic content, and antioxidant capacity of Tanacetum densum subsp. laxum and Tanacetum densum subsp. amani, to compare the effect of altitude on the biochemical content and to compare systematically by using fatty acids and phenolics. This study showed that palmitic acid (C16:0) and stearic acid (C18:0) are major sources of saturated fatty acid and oleic acid (C18:1 n9), and linoleic acid (18:2 n6c) and a-linolenic acid (C18:3 n3) are the principal unsaturated fatty acids in the two endemic Tanacetum densum taxa. Also, this study found that the unsaturated fatty acid content (60.11±1.61%) of Tanacetum densum subsp. laxum was higher than the unsaturated fatty acid content (44.13±1.28%) of Tanacetum densum subsp. amani. And also, the ω6/ω3 ratio of Tanacetum densum subsp. laxum (1.74) and Tanacetum densum subsp. amani (1.60) was found to be similar. However, this study determined that the lipid soluble vitamin and sterol content of two endemic Tanacetum taxa are low except for stigmasterol. Present study showed that catechin is principal phenolic in the Tanacetum densum taxa. This study also found that Tanacetum densum subsp. laxum and Tanacetum densum subsp. amani had the highest levels of catechin, vanillic acid, and caffeic acid content though the phenolic amounts, particularly catechin and quercetin, were dissimilar in the T. densum taxa. This study suggested that ecological conditions such as altitude may affect the biochemical content of two endemic Tanacetum densum taxa. Furthermore, the current study determined that two endemic Tanacetum L. taxa had potent radical scavenging capacities and found a correlation between total phenolics and antioxidant activity.


1977 ◽  
Vol 166 (3) ◽  
pp. 565-570 ◽  
Author(s):  
J. M. Haslam ◽  
Norman F. Fellows

1. The fatty acid composition of the ole-1 and ole-1 petite mutants of Saccharomyces cerevisiae was manipulated by growing the organism in the presence of defined supplements of Tween 80 or by allowing cells that had first been grown in the presence of Tween 80 to deplete their unsaturated fatty acids by sequent growth in the absence of Tween 80. 2. The transition temperature of Arrhenius plots of mitochondrial ATPase (adenosine triphosphatase) increases as the unsaturated fatty acid content is lowered. 3. Cells require larger amounts of unsaturated fatty acids to grow on ethanol at lower temperatures. 4. Cells that stop growing owing to unsaturated fatty acid depletion at low temperatures are induced to grow further by raising the temperature and this results in a further depletion of unsaturated acids. This is due to a higher rate, but not a greater efficiency, of mitochondrial ATP synthesis. 5. Arrhenius plots of the passive permeability of mitochondria to protons between 4 and 37°C are linear. The rate and the Arrhenius activation energy of proton entry increase greatly as the unsaturated fatty acid content is lowered. 6. Unsaturated fatty acid depletion has the same effects on the proton permeability of ole-1 petite mitochondria, indicating that the mitochondrially synthesized subunits of the ATPase are not involved in the enhanced rates of proton entry. 7. The adenylate energy charge of depleted ole-1 cells is greatly decreased by growth on ethanol medium. 8. The adenylate energy charge of isolated mitochondria is also lowered by unsaturated fatty acid depletion. 9. The results confirm that unsaturated fatty acid depletion uncouples oxidative phosphorylation in yeast both in vivo and in vitro, and is a consequence of changes in the lipid part of the membrane.


2020 ◽  
Vol 13 (12) ◽  
pp. 456
Author(s):  
Tasuku Nawaji ◽  
Natsumi Yamashita ◽  
Haruka Umeda ◽  
Shuangyi Zhang ◽  
Naohiro Mizoguchi ◽  
...  

Zebrafish are used widely in biomedical, toxicological, and developmental research, but information on their xenobiotic metabolism is limited. Here, we characterized the expression of 14 xenobiotic cytochrome P450 (CYP) subtypes in whole embryos and larvae of zebrafish (4 to 144 h post-fertilization (hpf)) and the metabolic activities of several representative human CYP substrates. The 14 CYPs showed various changes in expression patterns during development. Many CYP transcripts abruptly increased at about 96 hpf, when the hepatic outgrowth progresses; however, the expression of some cyp1s (1b1, 1c1, 1c2, 1d1) and cyp2r1 peaked at 48 or 72 hpf, before full liver development. Whole-mount in situ hybridization revealed cyp2y3, 2r1, and 3a65 transcripts in larvae at 55 hpf after exposure to rifampicin, phenobarbital, or 2,3,7,8-tetrachlorodibenzo-p-dioxin from 30 hpf onward. Marked conversions of diclofenac to 4′-hydroxydiclofenac and 5-hydroxydiclofenac, and of caffeine to 1,7-dimethylxanthine, were detected as early as 24 or 50 hpf. The rate of metabolism to 4’-hydroxydiclofenac was more marked at 48 and 72 hpf than at 120 hpf, after the liver had become almost fully developed. These findings reveal the expression of various CYPs involved in chemical metabolism in developing zebrafish, even before full liver development.


2005 ◽  
Vol 67 (6) ◽  
pp. 1954-1965 ◽  
Author(s):  
Oliver Burk ◽  
Katja A. Arnold ◽  
Andreas K. Nussler ◽  
Elke Schaeffeler ◽  
Ekaterina Efimova ◽  
...  

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