Re: Methionine rant by johng ..... Rife Forum: Bio Resonance
Date: 3/14/2010 5:31:04 PM ( 10 years ago ago)
so it would seem that this fix should enable the body to excrete more metals, especially if methionine and perhaps selenium are supplemented.
I also realized that I was confusing the pathways, that methylation is one of six phase II pathways. The sulphur pathway is a seperate process for seperate toxins. for those like me who need a reminder of the big picure, here is a decent summary:
Phase II Detoxification
This is called the conjugation pathway, whereby the liver cells add another substance (eg. cysteine, glycine or a sulphur molecule) to a toxic chemical or drug, to render it less harmful. This makes the toxin or drug water-soluble, so it can then be excreted from the body via watery fluids such as bile or urine. Individual xenobiotics and metabolites usually follow one or two distinct pathways. There are essentially six phase II detoxification pathways:
· Glutathione conjugation
· Amino acid conjugation
The conjugation molecules are acted upon by specific enzymes to catalyse the reaction step. Through conjugation, the liver is able to turn drugs, hormones and various toxins into excretable substances. For efficient phase two detoxification, the liver cells require sulphur-containing amino acids such as taurine and cysteine. The nutrients glycine, glutamine, choline and inositol are also required for efficient phase two detoxification.
A primary phase II detoxification route is conjugation with glutathione (a tripeptide composed of three amino acids--cysteine, glutamic acid, and glycine). Glutathione conjugation produces water-soluble mercaptates which are excreted via the kidneys. The elimination of fat-soluble compounds, especially heavy metals like mercury and lead, is dependent upon adequate levels of glutathione, which in turn is dependent upon adequate levels of methionine and cysteine. When increased levels of toxic compounds are present, more methionine is utilized for cysteine and glutathione synthesis. Methionine and cysteine have a protective effect on glutathione and prevent depletion during toxic overload. This, in turn, protects the liver from the damaging effects of toxic compounds and promotes their elimination.
Glutathione is also an important antioxidant. This combination of detoxification and free radical protection, results in glutathione being one of the most important anticarcinogens and antioxidants in our cells, which means that a deficiency is cause of serious liver dysfunction and damage. Exposure to high levels of toxins depletes glutathione faster than it can be produced or absorbed from the diet. This results in increased susceptibility to toxin-induced diseases, such as cancer, especially if phase I detoxification system is highly active. Disease states due to glutathione deficiency are not uncommon.
A deficiency can be induced either by diseases that increase the need for glutathione, deficiencies of the nutrients needed for synthesis, or diseases that inhibit its formation. Smoking increases the rate of utilization of glutathione, both in the detoxification of nicotine and in the neutralization of free radicals produced by the toxins in the smoke. Glutathione is available through two routes: diet and synthesis. Dietary glutathione (found in fresh fruits and vegetables, cooked fish, and meat) is absorbed well by the intestines and does not appear to be affected by the digestive processes. Dietary glutathione in foods appears to be efficiently absorbed into the blood. However, the same may not be true for glutathione supplements.
In healthy individuals, a daily dosage of 500 mg of vitamin C may be sufficient to elevate and maintain good tissue glutathione levels. In one double-blind study, the average red blood cell glutathione concentration rose nearly 50% with 500 mg/day of vitamin C. Increasing the dosage to 2,000 mg only raised red blood cell (RBC) glutathione levels by another 5%. Vitamin C raises glutathione by increasing its rate of synthesis. In addition, to vitamin C, other compounds which can help increase glutathione synthesis include N-acetylcysteine (NAC), glycine, and methionine. In an effort to increase antioxidant status in individuals with impaired glutathione synthesis, a variety of antioxidants have been used. Of these agents, only Mega H-, vitamin C and NAC have been able to offer some possible benefit.
Over the past 5-10 years, the use of NAC and glutathione products as antioxidants has become increasingly popular among nutritionally oriented physicians and the public. While supplementing the diet with high doses of NAC may be beneficial in cases of extreme oxidative stress (e.g. AIDS, cancer patients going through chemotherapy, or drug overdose), it may be an unwise practice in healthy individuals.
Amino acid conjugation
Several amino acids (glyucine, taurine, glutamine, arginine, and ornithine) are used to combine with and neutralize toxins. Of these, glycine is the most commonly utilized in phase II amino acid detoxification. Patients suffering from hepatitis, alcoholic liver disorders, carcinomas, chronic arthritis, hypothyroidism, toxemia of pregnancy, and excessive chemical exposure are commonly found to have a poorly functioning amino acid conjugation system. For example, using the benzoate clearance test (a measure of the rate at which the body detoxifies benzoate by conjugating it with glycine to form hippuric acid, which is excreted by the kidneys), the rate of clearance in those with liver disease is 50% of that in healthy adults.
Even in normal adults, a wide variation exists in the activity of the glycine conjugation pathway. This is due not only to genetic variation, but also to the availability of glycine in the liver. Glycine, and the other amino acids used for conjugation, become deficient on a low-protein diet and when chronic exposure to toxins results in depletion.
Methylation involves conjugating methyl groups to toxins. Most of the methyl groups used for detoxification come from S-adenosylmethionine (SAM). SAM is synthesized from the amino acid methionine, a process which requires the nutrients choline, the active form of B12 --methyl cobalamin, and the active form of folic acid --5-methyltetrahydrofolate. SAM is able to inactivate estrogens (through methylation), supporting the use of methionine in conditions of estrogen excess, such as PMS. Its effects in preventing estrogen-induced cholestasis (stagnation of bile in the gall bladder) have been demonstrated in pregnant women and those on oral contraceptives. In addition to its role in promoting estrogen excretion, methionine has been shown to increase the membrane fluidity that is typically decreased by estrogens, thereby restoring several factors that promote bile flow. Methionine also promotes the flow of lipids to and from the liver in humans. Methionine is a major source of numerous sulfur-containing compounds, including the amino acids cysteine and taurine.
Sulfation is the conjugation of toxins with sulfur-containing compounds. The sulfation system is important for detoxifying several drugs, food additives , and, especially, toxins from intestinal bacteria and the environment. In addition to environmental toxins, sulfation is also used to detoxify some normal body chemicals and is the main pathway for the elimination of steroid and thyroid hormones. Since sulfation is also the primary route for the elimination of neurotransmitters, dysfunction in this system may contribute to the development of some nervous system disorders.
Many factors influence the activity of sulfate conjugation. For example, a diet low in methionine and cysteine has been shown to reduce sulfation. Sulfation is also reduced by excessive levels of molybdenum or vitamin B6 (over about 100 mg/day). In some cases, sulfation can be increased by supplemental sulfate, extra amounts of sulfur-containing foods in the diet, and the amino acids taurine and glutathione.
Conjugation of toxins with acetyl-CoA is the primary method by which the body eliminates sulfa drugs. This system appears to be especially sensitive to genetic variation, with those having a poor acetylation system being far more susceptible to sulfa drugs and other Antibiotics . While not much is known about how to directly improve the activity of this system, it is known that acetylation is dependent on thiamine, pantothenic acid, and vitamin C.
Glucuronidation, the combining of glucuronic acid with toxins, in Phase II can be reversed by Beta glucuronidase enzymes produced by pathological bacteria and cause toxins to be reabsorbed increasing toxicity. Many of the commonly prescribed drugs are detoxified through this pathway. It also helps to detoxify aspirin, menthol, vanillin (synthetic vanilla), food additives such as benzoates , and some hormones. Calcium d-glucurate, a natural ingredient found in certain vegetables and fruits can inhibit beta glucuronidase activity resulting in increased elimination of toxins.
Nutrients needed by phase II detoxification enzymes
Glutathione conjugation: Glutathione Precursors (Cysteine, Glycine, Glutamic Acid, and co-factors), Essential Fatty Acids (Black Currant Seed Oil, Flax Seed Oil, EPA), Parathyroid Tissue
Amino acid conjugation: Glycine
Methylation: Methionine, Co-factors (Magnesium, Folic Acid, B-12, Methyl Donors)
Sulfation: Molybdenum, Cysteine and precursor (Methionine), Co-factors (B-12, Folic Acid, Methyl Donors, Magnesium, B-6/P-5-P), MSM
Acetylation: Acetyl-CoA, Molybdenum, Iron, Niacinamide, B-2
Glucuronidation: Glucuronic acid, Magnesium
Glycination: Arginase Enzyme, Glycine, Gly Co-factors (Folic Acid, Manganese, B-2, B-6/P-5-P)
Inducers of phase II detoxification enzymes
Glutathione conjugation: Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil)
Amino acid conjugation: Glycine
Methylation: Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12)
Sulfation: Cysteine, methionine, taurine
Acetylation: None found
Glucuronidation: Fish oils, cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods
Inhibitors of phase II detoxification enzymes
Glutathione conjugation: Selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency
Amino acid conjugation: Low protein diet
Methylation: Folic acid or vitamin B12 deficiency
Sulfation: Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), molybdenum deficiency
Acetylation: Vitamin B2, B5, or C deficiency
Glucuronidation: Aspirin, probenecid
Sulfoxidation is the process by which the sulfur-containing molecules in drugs and foods are metabolized. It is also the process by which the body eliminates the sulfite food additives used to preserve many foods and drugs. Various sulfites are widely used in potato salad (as a preservative), salad bars (to keep the vegetables looking fresh), dried fruits ( sulfites keep dried apricots orange), and some drugs. Normally, the enzyme sulfite oxidase metabolizes sulfites to safer sulfates, which are then excreted in the urine. Those with a poorly functioning sulfoxidation system, however, have an increased ratio of sulfite to sulfate in their urine. The strong odor in the urine after eating asparagus is an interesting phenomenon because, while it is unheard of in China, 100% of the French have been estimated to experience such an odor (about 50% of adults in the U.S. notice this effect). This example is an excellent example of genetic variability in liver detoxification function. Those with a poorly functioning sulfoxidation detoxification pathway are more sensitive to sulfur-containing drugs and foods containing sulfur or sulfite additives. This is especially important for asthmatics, which can react to these additives with life-threatening attacks. Molybdenum helps asthmatics with an elevated ratio of sulfites to sulfates in their urine because sulfite oxidase is dependent upon this trace mineral.
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