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LIVER DETOXIFICATION

The liver plays a key role in most metabolic processes, especially detoxification. The liver neutralizes a wide range of toxic chemicals, both those produced internally and those coming from the environment. The liver plays several roles in detoxification: it filters the blood to remove large toxins, synthesizes and secretes bile full of cholesterol and other fat-soluble toxins, and enzymatically disassembles unwanted chemicals. This enzymatic process usually occurs in two steps referred to as phase I and phase II . Phase I either directly neutralizes a toxin, or modifies If the phase II detoxification systems are not the toxic chemical to form activated working adequately, these intermediates can intermediates which are then neutralized by cause substantial damage, including the one of more of the several phase II enzyme initiation of carcinogenic processes. People systems. with a very active phase I detoxification Proper functioning of the liver's detoxification system coupled with slow or inactive phase systems is especially important for the II enzymes are termed pathological prevention of cancer. The level of exposure to detoxifiers . environmental carcinogens varies widely, as Phase I detoxification of most chemical does the efficiency of the detoxification toxins involves a group of enzymes which, enzymes, particularly phase II. High levels of collectively, have been named cytochrome exposure to carcinogens coupled with slow P450 . Some 50-100 enzymes make up the detoxification enzymes significantly increases cytochrome P450 system . Each enzyme susceptibility to cancer. works best in detoxifying certain types of Phase I Detoxification chemicals, but with considerable overlap in activity among the enzymes. The liver's third role in detoxification involves The activity of the various cytochrome a two-step enzymatic process for the P450 enzymes varies significantly from one neutralization of unwanted chemical individual to another, based on genetics, the compounds. These not only include drugs, individual's level of exposure to chemical pesticides, and toxins from the gut, but also toxins, and his or her nutritional status. normal body chemicals such as hormones and Since the activity of cytochrome P450 inflammatory chemicals (e.g. histamine ) varies so much, so does an individual's risk which become toxic if allowed to build up. for various diseases. This helps to explain Phase I enzymes directly neutralize some why some people can smoke with only chemicals, but most are converted to modest damage to their lungs, while others intermediate forms that are then processed by develop lung cancer after only a few phase II enzymes. These intermediate forms decades of smoking. are much more chemically active and therefore more toxic.

Patients with underactive phase I This conjugation reaction either neutralizes detoxification will experience caffeine the toxin or makes the toxin more easily intolerance, intolerance to perfumes and other excreted through the urine or bile. Phase II environmental chemicals, and an increased enzymes act on some toxins directly, while risk for liver disease, while those with an others must first be activated by the phase I overactive system will be relatively unaffected enzymes. There are essentially six phase II by caffeine drinks. One way of objectively detoxification pathways: determining the activity of phase I is to · Glutathione conjugation measure how efficiently a person detoxifies · Amino acid conjugation caffeine. Caffeine is an example of a chemical · Methylation directly neutralized by phase I. Making a toxin · Sulfation water-soluble allows its excretion by the · Acetylation kidneys . · Glucuronidation Transforming a toxin to a more chemically reactive form makes it more easily Acetaminophen and salicylic acid are a way metabolized by the phase II enzymes. of objectively determining the activity of phase II. A significant side-effect of phase I In order to work, these enzyme systems detoxification is the production of free need nutrients both for their activation and radicals as the toxins are transformed-- for to provide the small molecules they add to each molecule of toxin metabolized by phase the toxins. In addition, they utilize I, one molecule of free radical is generated. metabolic energy to function and to Without adequate free radical defenses, every synthesize some of the small conjugating time the liver neutralizes a toxin exposure, it is molecules. Thus, mitochondrial damaged by the free radicals produced. dysfunction, such as found in chronic fatigue syndrome, a magnesium deficiency The most important antioxidant for or physical inactivity, can cause phase II neutralizing the free radicals produced in detoxification to slow down, allowing the phase I is glutathione . In the process of build-up of toxic intermediates. neutralizing free radicals, however, glutathione (GSH) is oxidized to glutathione REQUIRED SAMPLE: disulfide (GSSG). Glutathione is required for Phase I: one of the key phase II detoxification Saliva after 2h consumption of caffeine * processes. When high levels of toxin exposure produce so many free radicals from phase I Phase II: detoxification that the glutathione is depleted, Urine collection during 10 h (night) after the phase II processes dependent upon consumption of 650 mg acetaminophen, glutathione stop. and 500 mg of salicylic acid. *

Phase II Detoxification *Request sampling procedure for more Phase II detoxification typically involves details. conjugation in which various enzymes in the TRANSPORT CONDITIONS: liver attach small chemicals to the toxin. Send chilled and keep frozen.