Dear Roxie60,
I empathize with your situation (that you explained 2 posts above) and I hope things get better.
I don't know of anything that would help, because I'm just floundering around in this area myself.
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Can someone tell me/show me the risk allele for ACAT 1-02? I have seen both A and G being shown as the risk allele, they both cant be.
What source says that G is the risk allele?
What I have seen is:
majority's alleles: GG (CC)
minority's alleles and risk alleles: AA (TT)
Yasko:
"ACAT plays a role in cholesterol and other lipid balance in the body, helping to prevent the
accumulation of excess cholesterol in certain parts of the cells in the body. ACAT is also involved in energy generation in the body. It is involved in helping to allow protein, fats and carbohydrates from food to be converted into an energy form that can be used by your body. In addition, lack of ACAT may also cause a depletion of B12, which is needed for the “long route” around the methylation cycle". // Yasko says this is a First Priority mutation - read more in her autism book chapter 6 step 2 part 1 and workbook page 76.
"This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone."
ncbi.nlm.nih.gov/gene summary
varioius quotes from people here:
"ACAT is a gene mutation related to fat metabolism and energy conversion. // Yasko says to treat the SNPs in a certain order. SHMT/ACAT, CBS, MTHFR, MTR/MTRR, BHMT, MAO A, SUOX, NOS, VDR. // the ACAT & SHMT. My doctor wants to know those two the most since these trump the MTHFR's and even the CBS! I guess the ACAT is horrible for gut issues, mitochondrial problems, urinary irritation, & kidney & bladder stones, the latter being due, I think, to oxalates // I am finding 4 hydroxylation of estrogen problems correlates with ACAT, CYP1B1, and downstream, SOD2 mutations. I am also finding other cholesterol mutations correlate with ACAT. I knew a homozygous ACAT mutation was relatively rare, but I had no idea that it could affect estrogen metabolism. // For ACAT, Yasko has an "everything but the kitchen sink" formula called ACAT/BHMT. the supplementation for ACAT is pretty complex (like 8 or 9 supps) // rs3741049 - ACAT1-02 (Risk Allele: A) Plays a major role in ketone body metabolism. Defects cause a 3-ketothiolase deficiency. Yasko believes it will cause an increase in gut bugs (particularly clostridia) as well as elevated fatty acid metabolites. //"
"ACAT1-02 (acetyl coenzyme A acetyltransferase) plays a role lipid metabolism and energy generation. It can also deplete B12. As with CBS, Dr. Yasko views this as a first priority mutation. Going by Yasko's clinical experience, she says to address them first if you have elevated iron on a UEE, elevated iron on a UEE test, Short Chain Fatty Acid (SCFA) imbalances on a CSA test, suberic acid, beta hydroxyl methylglutaric acid, or other ketone and fatty acid metabolites imbalances on a MAP or OAT test; or if there are severe gut issues or muscle weakness (which can be related to aluminum retention)". She says people with ACAT or SHMT are more likely to experience gut dysbiosis. Because of disrupted flora, microbes may have an affinity for and retain toxic metals. Stabilizing the gut environment is very important."
GeneticGenie
"ACAT is involved in cholesterol and energy metabolism, helping to mediate the conversion of foodstuffs into biological energy. ACAT dysfunction may lead to B12 deficiency. Right now, I do not understand ACAT well and am not sure how important this is."
Heartfixer site
"Plays a major role in ketone body metabolism. Defects cause a 3-ketothiolase deficiency."
SNPedia
from a Yasko book (I don't know which) quoted by PhoenixRising member Star-Anise:
"People with the SHMT and/or ACAT mutations sometimes have a greater tendency to experience gut dysbiosis and imbalanced flora. Until the flora are balanced, there’s a risk that the undesirable microbes will retain toxic metals. So, for those with ACAT or SHMT as well as other mutations (such as the MTHFR A1298C) that confer a greater likelihood of retaining aluminum, it is essential, prior to addressing these other mutations, to first stabilize the general gut environment via SHMT and/or ACAT support, by using supplements in the MPA received with your test results.
ACAT, (Acetyl-Coenzyme A acetyltransferase) impacts critical pathways and hence functional areas of human biochemistry in several ways, including:
• Helping to form cholesterol
• Assuring lipid balance and fluidity in the cell membranes, which in turns impacts neurological function
• Contributing to energy production via the Krebs cycle and its impact on the mitochondria, which signal cellular activity and supply cellular energy
• Mediating the accumulation of oxalates, which, in excess, can contribute to kidney stones and other health problems
ACAT contributes to cholesterol synthesis and membrane lipid balance. Bile acids are first synthesized from cholesterol and next conjugated to taurine. High taurine levels (often seen with ACAT) may reflect a lack of bile acids for conjugation. Since bile salts have been shown to increase ACAT activity, they may help ACAT issues. In addition, policosanol may help with membrane lipid balance and fluidity, which impacts neurological function. The next portion of the pathway that may be impacted by ACAT is the level of acetyl CoA, which feeds into the top of the TCA cycle (also called the Krebs cycle) at 12:00. Benfotiamine, riboflavin, and pantothenic acid support the reactions between pyruvate and the TCA cycle. In addition, a low dose of alpha lipoic acid (ALA) has been shown to replace acetyl CoA in certain reactions. Either a sprinkle of the ALA supplement or the topical ALA lotion can be used. More is not always better when it comes to support with ALA, although in some cases high dose ALA has been reported to have wonderful effects. ALA use should be based on both genetics and biochemical lab data.
A block at the acetyl CoA point of the Krebs/TCA cycle can also lead to both an accumulation of oxalates and increased levels of methylmalonic acid (MMA). To keep the cycle moving, the oxalates at 11:00 must combine with acetyl CoA coming in at 12:00. Low-dose vitamin K and lactoferrin help with that activity.
If both SHMT+ and ACAT + are present, begin with SHMT support first, and once that is in place, layer in ACAT support. Since high methionine levels appear to accompany ACAT mutations, SAMe, bile salts, glutathione (GSH,) and CoQ10 all can help to support the conversion of methionine. Curcumin and quercetin help shift the transulfuration pathway toward GSH. Since too much GSH can feed back and inhibit an enzyme that shunts to glutathione, I like to support the overall pathway rather than merely adding GSH."
PhoenixRising member Valentijn does not think the AA mutation is something to worry about:
"There is 0 research about that SNP. The odds of it being relevant are pretty small (AA is common in some populations - up to 20%). You might as well roll a die or use your horoscope to decide if it's having any impact at all. "
My response to that was:
"I see two smallish samples where it's around 20% (both marked "Asian"), and two smallish ones where it's around 14% (one marked "Asian", and the other is Chinese people who are living in Denver, so basically also "Asian").
http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3741049.
Otherwise, the T/T / A/A is pretty unusual in other ethnicities/geographies."
http://forums.phoenixrising.me/index.php?threads/cbs-acat-bile-salts.24417
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