Close-up TV News - Prolotheray lecture

Reversing Hypertension

Heavy Metals and all diseases

Close-Up TV News - Dr. Calapai's approach

News 12 Interview: Parkinson’s Disease, Glutathione and Chelation Therapy

News 12 Interview: Platelet-rich plasma therapy

Prolotherapy Interview News 12

News 12 Interview: Diabetes and Weight Loss
Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer's and Parkinson's diseases. *

There are two functional Omega class glutathione transferase (GST) genes in humans. GSTO1 is polymorphic with several coding region alleles, including an A140D substitution, a potential deletion of E155 and an E208K substitution. GSTO2 is also polymorphic with an N142D substitution in the coding region. We investigated the effect of these variations on the enzyme's thioltransferase, dehydroascorbate reductase, monomethylarsonate reductase and dimethylarsonate reductase activities. Variant proteins were expressed in Escherichia coli and purified by Ni-agarose affinity chromatography. GSTO2-2 was insoluble and had to be dissolved and refolded from 8 M urea. The A140D and E208K substitutions in GSTO1-1 did not alter specific activity.

The deletion of E155 caused a two- to three-fold increase in the specific activity with each substrate. This deletion also caused a significant decrease in the enzyme's heat stability. The E155 deletion has been linked to abnormal arsenic excretion patterns; however, the available data do not clearly identify the cause of this abnormality. We found that GSTO2-2 has activity with the same substrates as GSTO1-1, and the dehydroascorbate reductase activity of GSTO2-2 is approximately 70-100-fold higher than that of GSTO1-1. The polymorphic N142D substitution had no effect on the specific activity of the enzyme with any substrate. The most notable feature of GSTO2-2 was its very high dehydroascorbate reductase activity, which suggests that GSTO2-2 may significantly protect against oxidative stress by recycling ascorbate. A defect in ascorbate metabolism may provide a common mechanism by which the Omega class GSTs influence the age-at-onset of Alzheimer's and Parkinson's diseases.

* Legal Disclaimer: Chelation and Hyperbaric Therapy, Stem Cell Therapy, and other treatments and modalities mentioned or referred to in this web site are medical techniques that may or may not be considered “mainstream”. As with any medical treatment, results will vary among individuals, and there is no implication or guarantee that you will heal or achieve the same outcome as patients herein.

As with any procedure, there could be pain or other substantial risks involved. These concerns should be discussed with your health care provider prior to any treatment so that you have proper informed consent and understand that there are no guarantees to healing.

THE INFORMATION IN THIS WEBSITE IS OFFERED FOR GENERAL EDUCATIONAL PURPOSES ONLY AND DOES NOT IMPLY OR GIVE MEDICAL ADVICE. No Doctor/Patient relationship shall be deemed to have arisen simply by reading the information contained on these pages, and you should consult with your personal physician/care giver regarding your medical treatment before undergoing any sort of treatment or therapy.

Published on 10-13-2008
Authors: Schmuck, Erica M. *; Board, Philip G.; Whitbread, Astrid K.; Tetlow, Natasha; Cavanaugh, Juleen A.; Blackburn, Anneke C.; Masoumi, Amir
Source: Pharmacogenetics & Genomics. 15(7),:493-501, July 2005.