Digestive System Physiology
Phase I either directly neutralizes a toxin, or modifies the toxic chemical to form activated intermediates which are then neutralized by one of more of the several phase II enzyme systems. Another source of ocean pollution by sewage-related waste is the disposal of biosolids, a semisolid byproduct of the sewage treatment process, often called sludge. Recent research shows that the cytochrome P enzyme systems are also found in other parts of the body, especially the brain cells. Also, the chloride-bicarbonate exchanger biological transport protein relies on the chloride ion to increase the blood's capacity of carbon dioxide, in the form of the bicarbonate ion. This will result in high levels of damaging free radicals being produced. Lipotropic nutrients choline, methionine, betaine, folic acid, vitamin B12 Sulfation:
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Otherwise, the unhealthy bacteria cells can proliferate and make us sick, leading to bad digestion, disease and even poor mood health. One of those that is essential for our health, including digestion, is magnesium. Magnesium is found in all plant-based foods lucky us! Organic will ensure your foods have the most mineral content and will keep your body free from harmful chemicals and pesticides that could possibly alter your digestive tract. Plant-based sources of magnesium are abundant and are better sources than animal foods that your body can easily use.
Here are some of the most award-worthy: See more magnesium-rich foods here. This important mineral is also necessary for healthy nervous system function that affects digestion. The effect this has on your gut is huge. Calcium and magnesium compete for absorption in the body, so consider eating foods rich in both minerals. Two great examples are greens and seeds. Calcium is found rich in many plant-based foods.
Some of the highest sources are: Amaranth and teff are also two super-seeds pseudograins that offer incredible sources of calcium. Fortified almond milks are also a great source and if you eat soy, tofu and soy milk are also good sources. See more sources of plant-based calcium here. Vitamin D, known as the sunshine vitamin , is one of the most beneficial nutrients for your gut.
Calcium is also better absorbed with adequate Vitamin D intake during the digestive process, making Vitamin D even more important. A Vitamin D deficiency can lead to weak bones or osteoporosis, colon problems, depression, and general digestive issues because of the way this vitamin affects so much our our nervous system, digestive system, and bone health.
Getting enough in a plant-based diet is difficult without supplementation or fortified options. Mushrooms are the only true source of high adequate vitamin D intake outside of products made with Vitamin D2 often derived from plant-based yeasts. Everyone will need different amounts of this vitamin, so consider supplementation to get the most benefits. For now, start eating more mushrooms; just be sure to buy organic since mushroom is a fungi and pesticide-laden options could harm your health more than help.
Vitamin B12 is a hot topic when it comes to nutrient needs on a plant-based diet and any diet, really. Derived from bacteria from the soil, this nutrient and other B vitamins, all affect digestion due to their effects on metabolism, absorption of nutrients, and mainly due to their effect on the central nervous system. All B vitamins help optimize brain and central nervous system health, which improves your mood, lowers anxiety, and can even help you focus better and improve your energy.
Vitamin B6 and Vitamin 12 are two of the best nutrients for this matter, but all B vitamins are equally important. Lucky for us, Vitamin B rich foods are found abundantly in plant-based foods.
Here are some of the best: Nutritional yeast, spirulina and fortified non-dairy milks or soy products are some of the only food sources of Vitamin B12, however. Good picture of Phase II conjugation reactions: Phase II detoxification typically involves conjugation in which various enzymes in the liver attach small chemicals to the toxin.
This conjugation reaction either neutralizes the toxin or makes the toxin more easily excreted through the urine or bile. Phase II enzymes act on some toxins directly, while others must first be activated by the phase I enzymes. There are essentially six phase II detoxification pathways: In order to work, these enzyme systems need nutrients both for their activation and to provide the small molecules they add to the toxins.
In addition, they utilize metabolic energy to function and to synthesize some of the small conjugating molecules. Thus, mitochondrial dysfunction, such as found in chronic fatigue syndrome, a magnesium deficiency or physical inactivity, can cause phase II detoxification to slow down, allowing the build-up of toxic intermediates.
Glutathione, vitamin B6 Amino acid conjugation: Cysteine, methionine, molybdenum Acetylation: Brassica family foods cabbage, broccoli, Brussels sprouts ; limonene-containing foods citrus peel, dill weed oil, caraway oil Amino acid conjugation: Lipotropic nutrients choline, methionine, betaine, folic acid, vitamin B12 Sulfation: Cysteine, methionine, taurine Acetylation: Fish oils, cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods.
Inhibition of phase II detoxification is not desired, especially in those with Gilbert's Syndrome, as these enzymes are already inhibited. 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.
Vitamin B2, B5, or C deficiency Glucuronidation: Glucuronidation is a major phase II detoxification pathway in which the sugar moiety of UDP-glucuronic acid is covalently linked to a xenobiotic or endobiotic, facilitating its removal from the body in the urine or bile. The directed excretion of glucuronides from the lumen of the endoplasmic reticulum ER to the plasma membrane and the exterior of the cell is an important regulated process.
Impaired excretion leads to liver damage. Specific transporters for excretion of glucuronides have been implicated in lever cell function in ER and bile canaliculus. Polycyclic aromatic hydrocarbons, steroid hormones, some nitrosamines, heterocyclic amines, some fungal toxins, and aromatic amines.
It also removes "used" hormones, such as estrogen and T4 thyroid hormone that are produced naturally by the body. 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. Glucuronidation appears to work well, except for those with Gilbert's syndrome--a relatively common syndrome characterized by a chronically elevated serum bilirubin level 1.
The condition is usually without serious symptoms, although some patients do complain about loss of appetite, malaise, and fatigue typical symptoms of impaired liver function. The main way this condition is recognized is by a slight yellowish tinge to the skin and white of the eye due to inadequate metabolism of bilirubin, a breakdown product of hemoglobin. The activity of UDPGT is increased by foods rich in the monoterpene limonene citris peel, dill weed oil, and caraway oil.
Methionine, administered as SAM, has been shown to be quite beneficial in treating Gilbert's syndrome. Glucuronidation is a major inactivating pathway for a huge variety of exogenous and endogenous molecules, including drugs, polluants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids and bile acids. These enzymes are primarily found in the endoplasmic reticulum of many tissues, with the liver being, quantitatively, the most significant site of glucuronidation.
In addition to a wide tissue distribution of UGTs, different isozymes can be preferentially expressed in specific tissues. Furthermore, polymorphic expression of certain UGTs has also been observed 2. Of these three families UGT1 and UGT2 have been shown to catalyze the glucuronidation of a wide variety of xenobiotic substrates, with UGT1 being more active in the glucuronidation of amines 3,4.
Aryl- and alkylamines, sulfonamides, heterocyclic amines and hydroxylated compounds have all been reported to undergo glucuronidation in many animal species and humans. The primary function of UGTs is to eliminate substrates from the body via urine and feces by catalyzing the formation of hydrophilic glucuronide conjugates 5.
UGT detoxifies many xenobiotics. The UGT1 family specializes in processing amines, arylamines and alkylamines, sulfonamides, heterocyclic amines and hydroxylated compounds. UDP-glucuronosyltransferases UGTs belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds including bilirubin, hormones, various drugs as well as environmental carcinogens.
Glucuronidation predominantly serves as a pathway for elimination of the different glucuronidated compounds. Seventeen human UGT transcripts have been identified thus far, and the UGT proteins are differentially expressed in a wide-range of human tissues. Most of the UGTs are expressed in the liver as well as other extrahepatic tissues; however, some are exclusively extrahepatic Table 1. The tissue specific regulation of UGTs ensures a unique complement of UGT proteins to various tissues, and defines the capacity of each tissue's ability to eliminate or inactivate various exogenous and endogenous substrates.
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: 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 mg of vitamin C may be sufficient to elevate and maintain good tissue glutathione levels.
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. Over the past 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. AIDS, cancer patients going through chemotherapy, or drug overdose , it may be an unwise practice in healthy individuals. Glutathione-S-transferase detoxifies many water-soluble environmental toxins, including many solvents, herbicides, fungicides, lipid peroxides, and heavy metals e. The various forms of GST work together to eliminate toxins.
Decreased glutathione conjugation capacity may incrase toxic burden and increase oxidative stress. Glutathione-S-tranferase affords protection against oxidative stress especially by reducing hydrogen peroxide and by regenerating oxidized vitamins C and E.
GST also detoxifies electrophilic compounds including solvents, herbicides, fungicides, polycyclic aromatic hydrocarbons and heavy metals Mercury, Lead, and Cadmium. Decreased glutathion conjugation capacity may increase toxic burden and increase oxidative stress resulting in a greater risk for various cancers and fatigue syndromes, especially if exposed to toxic compounds.
Regardless of genotype, increasing the body's production of glutathione will reduce oxidative stress and afford greater protection against a wide array of toxins.
Numerous supplements can help raise glutathione levels including liberal consumption of colorful vegetables and fruits, vitamin C, n-acetylcysteine and milk thistle. Liberally consume bassica vegetables broccoli, cauliflower, kale, cabbage, bok choi, etc. Vitamin E supplementation may also be helpful.
COnsult your healthcare provider to find the supplement regimen that best fits your overall health needs. If you smoke, stop.
Avoid exposure to herbicides, fungicides, insect sprays and industrial solvents. 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. Even in apparently normal adults, a wide variation exists in the activity of the glycine conjugation pathway. This is due no 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, vitamin B12, and folic acid.
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.
Catechol-O-methyl transferase is the enzyme primarily responsible for breaking down the neurotransmitters dopamine, epinephrine, and norepinephrine. Risk may be increased for some neuropsychiatric disorders, imparied estrogen metabolism, increased sensitivity to pain, and late-onset alcoholism.
Avoid excessive alcohol consumption; seek help if alcohol consumption is a health issue. Minimize sustained mental and environmental stress stress hormones require COMT for their degradation, thus can decrease the methylation of estrogen compounds. Ensure adequate intake of B vitamins, magnesium, and protein.
Epinephrine is the same as adrenaline, and norepinephrine is the same as noradrenaline. 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. 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.
Neurotransmitters, steroid hormones, certain drugs such as Acetaminophen also known as paracetamol ,and many xenobiotic and phenolic compounds.
And the polymorphism - the first one - that affects disposal of ephinephrine adrenaline , norepiniephrine noradrenaline , and dopamine. That struck true with me. When I get mad I have a hard time calming down. My own personal research and experience with dopamine reveals that it deals with the attention-switching threshold.
I often find myself obsessing in certain projects or games, and hard to shift out. If my liver cant dispose of those chemicals, that would explain that as well. Good lord that's a match. 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. N-acetyl Transferase detoxifies many environmental toxins, including tobacco smoke and exhaust fumes. Polymorphisms can result in slower than normal or faster than normal addition of an acetyl group to these toxins. Slow acetylators have a build up of toxins in the system and rapid acetylators add acetyl groups so rapidly that they make mistakes in the process.
Both slow and rapid acetylators are at increased risk for toxic overload if they are exposed to environmental toxins. If the toxin exposure is reduced, the risk is reduced. N-acetyltransferase 1 is found in extra-hepatic tissues, while NAT2 is found predominantly in the liver and the gut. Both are used in the Phase II acetylation of numerous environmental toxins, including heterocyclic aromatic amines.
Slow acetyleators do not clear toxins well and the resulting increased total toxic burden can increase the risk of lung, colon, breast, bladder, and head and neck cancers, though results have not been consistent in all studies. Urinary bladder cancer appears to have the most consistent association with low acetyleation.
Your risk of lung cancer is substantially higher than someone with normal NAT activity. Even occasional smoking or exposure to second hand smoke is harmful.
Liberal consumption of most vegetables and fruits but especially cruciferous vegetables broccoli, Brussels sprouts, cauliflower, watercress, and cabbage , garlic, onions, soy, grapes and berries will increase Phase II efficienty, including acetylation. Salicylates and benzoate are detoxified primarily through glycination.
Benzoate is present in many food substances and is widely used as a food preservative. Many other substances are detoxified as well via the glycine conjugation pathway. Patients suffering from xenobiotic overloads and environmental toxicity may not have sufficient amounts of glycine to cope with the amount of toxins they are carrying. Another potential problem occurs because the toxins transformed into activated intermediates by phase I are substantially more reactive.
Unless quickly removed from the body by phase II detoxification mechanisms, they can cause widespread problems, especially carcinogenesis. Therefore, the rate at which phase I produces activated intermediates must be balanced by the rate at which phase II finishes their processing.
People with a very active phase I detoxification system coupled with slow or inactive phase II enzymes are termed pathological detoxifiers. These people suffer unusually severe toxic reactions to environmental poisons. An imbalance between phase I and phase II can also occur when a person is exposed to large amounts of toxins or exposed to toxins for a long period of time.
In these situations, the critical nutrients needed for phase II detoxification are depleted, which allows the highly toxic activated intermediates to build up.