study notes in progress
(items particularly applicable to me are in orange)
NOTE ON TESTS:
- Many of these functions are measured in the GSDL Detoxification Profile. See my results from that test on 28 November 2001.
- In addition, the Genovations DetoxiGenomic Profile identifies polymorphisms (SNPs) in genes responsible for some of these functions. I had this test performed 22 June 2006; see my results from the DetoxiGenomic Profile.
Liver Phase I: functionalization (oxidation, reduction or hydrolysis reactions, increasing solubility of the substrate)
P450 Enzymes use oxygen to process many endogenous and exogenous subtances, adding a reactive group, such as hydroxyl radical, to the molecule being processed in order to enable Phase II to deal with it.
Pathological detoxifiers / Liver backlog
- Phase I produces more than Phase II can handle.
- highly sensitive to fumes eg paints, perfumes
- react adversely to various pharmaceutical drugs
- may react to drinking caffeine
- So should I try to inhibit Phase I?
- "May find it useful to include grapefruit juice in their diet" says Kimber
- grapefruit juice inhibits CYP3A4 for up to 72 hours (Julian Whitaker says all CYP3As, October 2002 Health & Healing, p.4)
- for other inhibitors see P450 Perturbation
- MiDobs on the AMALGAM list says "Someone who (still/now) has normal Phase I but poor Phase II sulfation, as a result of mercury poisoning, can take glucosamine sulfate while dealing with the mercury." [That's an interesting possibility, how can I check it?](see directions for access)
- from MiDobs@INTERNETWIS.COM
- message-ID: <199902281552.SM00141@default>
- Sun, 28 Feb 1999 14:50:18 -0800
- In "Looking at the Patient," (no longer on the Web) Han van den Braak mentioned that mineral deficiency commonly underlies "liver backlog" where Phase I is more active than Phase II.
Liver Phase II Conjugation (biotransformation of a lipophilic compound, by combining it with another substance, to a water-soluble compound able to be excreted)
Processes (Cofactors must be replenished through dietary sources)
- glucuronic acid
- commonly induced by multi-functional inducers
- can be supplemented with Calcium D-Glucarate
- is slower than sulfation
Acylation (peptide conjugation)
The amino acids glycine, taurine, glutamine, arginine, and ornithine combine with toxins to neutralize and eliminate them.
- Most common: glycine (the one Great Smokies tests)
- the most important route of detoxification for
- endogenous acids.
- many xenobiotic carboxylic acids
- "However, the first reaction of glycine conjugation in some cases is reported to involve a class of active intermediates implicated in toxicity."
- (from Reaction Mechanism of Amino Acid Conjugation and Determination of the Structure. Fumiyo KASUYA ( Faculty of Pharm aceutical Sciences, Kobe-gakuin University ( 518, Arise, Ikawadani, Nishi-ku, Kobe 651-2180, Japan) in J. Mass Spectrom. Soc. Jpn., 49(3), 89-95, 2001. English abstract )
- Rate-limiting enzyme: the medium chain acyl-CoA synthetase catalyzing the initial reaction of glycine conjugation. In addition, the stability of acyl-CoAs may be a determining factor.
- The amino acid conjugation system can become damaged by hepatitis, alcoholic liver disorders, carcinomas, chronic arthritis, hypothyroidism, toxemia of pregnancy, and excessive chemical exposures.
Glutathione conjugation (mercapturic acid synthesis)
- commonly induced by multi-functional inducers
- cofactors: Vitamin E, selenium
- "The cooperation of Vitamin E and selenium produces the vital antioxidant peptide enzyme selenium-glutathione-peroxidase. Appears to help stimulate the production of antibodies, and may stimulate synthesis of protein." Autism Center's Supplement Reference
- I feel sick for a couple hours after taking Vitamin E and selenium; does this mean I have trouble making glutathione or using it? It's better since I stopped taking cranberry juice extract, but not gone. It's also better if I get out of my office. If I take vitamin E without selenium, it doesn't happen; also I can take selenium for a few days before it starts.
- Necessary for regulating bone density [anabolism?]
- detoxifies (breaks down) estrogens
Multi-Functional Induction: substances inducing multiple Phase II processes
(Mono-functional induction is listed with the process it induces)
- rosemary (provokes a reaction)
- soy (provokes a reaction)
- brussels sprouts (can't eat much)
- Garlic oil (provokes a reaction)
- acetaminophen (provokes a reaction) See Acetaminophen Poisoning.
Methylation - takes place in every cell in the body
- Sulfation and glucuronidation go on here too. Some xenoestrogens inhibit these processes.
- Useful enzymes at tip of villi
- "Phase III" anti-porter activity: an energy-dependent efflux pump, which pumps xenobiotics out of a cell, thereby decreasing the intracellular concentration of xenobiotics. See reference 15 at Liska
- Counterproductive process: enterohepatic recirculation. Beta-glucoronidase bacteria remove conjugation moiety glocuronosyl side chain converting estrogens back to their original form and allowing them to reenter circulation.
General Detox Info:
- Herbs (These are mostly specific for the liver)
- Silymarin - has been helping me
- Artichoke (related to Silymarin) stimultes bile
- Dandelion (I believe I reacted to this when I tried it in '97.)
- NAC (N-Acetylcysteine) "not everybody tolerates NAC well." Steven Shackel
- "Scientists at the University of Minnesota have found that the two primary chemical components in lupulin [from hops] humulone and lupulune stimulate the production of liver enzymes that metabolize toxins." Bobbi A. McRaie, "Hops: Food, Shade, Flavoring and a Pillow for Your Head." The Herb Companion, April/May 1992, p. 62. (I have found similar statements around the Web but no documentation as yet.)
copyright © 2000 by Catherine Holmes Clark. Last updated 1 November 2005