Vitamin B6 (P5P) Is An ACC Inhibitor And May Treat Obesity

haidut

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It seems vitamin B6 is especially important for the metabolism of long-chain fatty acids, which include the dreaded EPA, DHA, and arachidonic acids. The dosages of P5P that inhibited ACC-1 and ACC-2 in vitro are close to physiological and what is achievable by supplementation. Typical concentrations of P5P in rat liver are around 100 microM as the study below shows, and that is without supplementation. Supplementing rats with the human equivalent dose of 10mg P5P increased concentrations in liver to 300 microM, so it looks like a dose of 10mg-20mg daily may have an effect on obesity or at least inhibit fatty acid elongation and oxidation.

http://www.jbc.org/content/280/51/41835.long

"...Mammalian isoforms of acetyl-CoA carboxylase (ACC-1 and ACC-2) play important roles in synthesis, elongation, and oxidation of long-chain fatty acids, and the possible significance of ACC in the development of obesity has led to interest in the development of inhibitors. Here, we demonstrate that pyridoxal phosphate (PLP) is a linear and reversible inhibitor of ACC-1 and ACC-2. ACC from rat liver and white adipose tissue (largely ACC-1) exhibited an IC50 of ∼200 μm, whereas ACC-2 from heart or skeletal muscle exhibited an IC50 exceeding 500 μm."
 
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Wouldn't this be why it helps during "essential" fatty acid "deficiency"?
 
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Well... you need elongase to make Mead's acid...
 
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Yeah Mead acid causes the redness in EFA deficiency
 

paymanz

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i think for a healthy person who just wants to loss some weight its favorable to inhibit ACC,but otherwise ACC seems a god thing from what i read on wikipedia:
The function of ACC is to regulate the metabolism of fatty acids. When the enzyme is active, the product, malonyl-CoA, is produced which is a building block for new fatty acids and can inhibit the transfer of the fatty acyl group from acyl CoA to carnitine with carnitine acyltransferase, which inhibits the beta-oxidation of fatty acids in the mitochondria.

ACC inhibits beta oxidation and carnitine....

i think some good quality fat that is made with this pathway is not bad.

ACC ,myelin Biotin as a treatment for multiple sclerosis (MS)
 
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haidut

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i think for a healthy person who just wants to loss some weight its favorable to inhibit ACC,but otherwise ACC seems a god thing from what i read on wikipedia:


ACC inhibits beta oxidation and carnitine....

i think some good quality fat that is made with this pathway is not bad.

ACC ,myelin Biotin as a treatment for multiple sclerosis (MS)

Inhbition of malonyl-CoA decarboxylase is a hot topic in cancer treatment right now. Google it for more info. Not saying it should be inhibited indiscriminately but increased synthesis of fatty acids is not something you want to continue chronically.
 
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Wouldn't a carbohydrate-heavy diet induce it?
 

haidut

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Wouldn't a carbohydrate-heavy diet induce it?

I think it can do it only if there is overproduction of acetyl-CoA, which is common in cancer and diabetes. Another reason to ensure the electron transport complex is working well, which is where methylene blue comes into play.
 
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I think it can do it only if there is overproduction of citrate, which is common in cancer and diabetes. Another reason to ensure the electron transport complex is working well, which is where methylene blue comes into play.

I see. Interesting.
 

haidut

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SolidSteele

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If Malonyl CoA is the mechanism by which beta oxidation is inhibited would suppressing ACC allow you to utilise glucose and fatty acids at the same time without restriction?
 
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