anne_likes_red
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Could and upset liver be a clue to Me/cfs?
- Thread starter Boba
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CSMLSM
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Just want to point out that TUDCA is a bile acid/salt, however I understand your point of improving the composition of bile.
Epsecially in the case of cholestasis which can be caused by thickening of the bile due to lack of bile acids in relation to cholesterol which is why the bile thickens and flow reduced within the ducts.
Bile acids/salts are like dish soap breaking up fats and emulsifying the fat in with the water. usually fat/oil/lipids do not mix with watery liquids.
datadragon
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The cytochrome P450 enzyme Cholesterol 7-hydroxylase (CYP7A1) plays a key role in maintaining lipid and bile salt homeostasis as it is the rate-limiting enzyme converting cholesterol to bile acids. The CYP7A1 level was dramatically reduced which is the rate limiting enzyme in bile acid synthesis. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep4.1129
It appears that CYP7A1 mRNA expression is greatly repressed (lowered) by Retinoic Acid (Vitamin A active metabolite) in both human hepatocytes and HepG2 cells A Genetic deficiency of CYP7A1 in humans leads to hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia. If its deficient instead due to a high retinoic acid level then you are inhibiting that enzyme that converts cholesterol to bile acids which may be yet another reason why fats, cholesterol, or triglycerides goes up from that https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903807/
The gene encoding alcohol dehydrogenase-1 (Adh1) greatly facilitates degradative metabolism of excess Vitamin A retinol into retinoic acid which may help protect against toxic effects of high dietary vitamin A intake or supplementation. (which requires Zinc.) https://portlandpress.com/biochemj/...lular-retinol-binding?redirectedFrom=fulltext
Since there are no known enzymes that can reduce retinoic acid to retinal, excessive or unneeded retinoic acid is not recycled back to retinol/retinyl ester and must be catabolized and eliminated from the body. This catabolism is catalyzed by one of several cytochrome P450 (CYP) enzymes which require magnesium. Any factor that lowers magnesium or cytochrome P450 enzymes can lead to excessive retinoic acid. https://www.jlr.org/article/S0022-2275(20)42124-8/fulltext
Over 600 enzyme systems require Magnesium as a cofactor to function optimally, including the cytochrome P450 enzymes (CYP450 https://www.liebertpub.com/doi/abs/10.1089/pai.1994.8.7
The innate immune response may involve the release of pro inflammatory cytokines, such as IL-6, which have the ability to suppress xenobiotic-metabolizing CYP450 enzymes https://www.xenotech.com/access-adm...-toll-like-receptor-9-agonist-in-hepatocytes/ Expression of CYP450 enzymes is downregulated in the hepatic tissue during the host response to inflammation or infection https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.2008.302
So bile production is impaired with liver disease, inflammation and infection, low mag and zinc to regulate the retinoic acid levels. Metals have been mentioned to also inhibit cytochrome P450 enzymes.
White, pale or gray stools may indicate a lack of bile. Taurine is a meat sourced amino acid not found in plant foods which is critical for the production of bile which might be low especially in vegan/vegetarian diets. Taurine (and sulfur) deficiency means bile production is impaired.
-David
It appears that CYP7A1 mRNA expression is greatly repressed (lowered) by Retinoic Acid (Vitamin A active metabolite) in both human hepatocytes and HepG2 cells A Genetic deficiency of CYP7A1 in humans leads to hyperlipidemia, including hypercholesterolemia and hypertriglyceridemia. If its deficient instead due to a high retinoic acid level then you are inhibiting that enzyme that converts cholesterol to bile acids which may be yet another reason why fats, cholesterol, or triglycerides goes up from that https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903807/
The gene encoding alcohol dehydrogenase-1 (Adh1) greatly facilitates degradative metabolism of excess Vitamin A retinol into retinoic acid which may help protect against toxic effects of high dietary vitamin A intake or supplementation. (which requires Zinc.) https://portlandpress.com/biochemj/...lular-retinol-binding?redirectedFrom=fulltext
Since there are no known enzymes that can reduce retinoic acid to retinal, excessive or unneeded retinoic acid is not recycled back to retinol/retinyl ester and must be catabolized and eliminated from the body. This catabolism is catalyzed by one of several cytochrome P450 (CYP) enzymes which require magnesium. Any factor that lowers magnesium or cytochrome P450 enzymes can lead to excessive retinoic acid. https://www.jlr.org/article/S0022-2275(20)42124-8/fulltext
Over 600 enzyme systems require Magnesium as a cofactor to function optimally, including the cytochrome P450 enzymes (CYP450 https://www.liebertpub.com/doi/abs/10.1089/pai.1994.8.7
The innate immune response may involve the release of pro inflammatory cytokines, such as IL-6, which have the ability to suppress xenobiotic-metabolizing CYP450 enzymes https://www.xenotech.com/access-adm...-toll-like-receptor-9-agonist-in-hepatocytes/ Expression of CYP450 enzymes is downregulated in the hepatic tissue during the host response to inflammation or infection https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.2008.302
So bile production is impaired with liver disease, inflammation and infection, low mag and zinc to regulate the retinoic acid levels. Metals have been mentioned to also inhibit cytochrome P450 enzymes.
White, pale or gray stools may indicate a lack of bile. Taurine is a meat sourced amino acid not found in plant foods which is critical for the production of bile which might be low especially in vegan/vegetarian diets. Taurine (and sulfur) deficiency means bile production is impaired.
-David
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