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Catechol-O-methyltransferase (COMT; EC 2.1.1.6) is one of several enzymes that degrade catecholamines (such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structure.[6] In humans, catechol-O-methyltransferase protein is encoded by the COMT gene.[7] Two isoforms of COMT are produced: the soluble short form (S-COMT) and the membrane bound long form (MB-COMT). As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines.[8] COMT was first discovered by the biochemist Julius Axelrod in 1957.[9]

https://en.wikipedia.org/wiki/Catechol-O-methyltransferase#cite_note-6

Reference 6 from above:

Unit Code 83301:
Catechol-O-Methyltransferase Genotype

Useful For
Early identification of patients who may show cognitive improvement with treatment for schizophrenia. This isassociated with the *2/*2 genotype.

Investigation of inhibitor dosing for decreasing L-DOPA metabolism.

Research use for assessing estrogen metabolism.

Clinical Information
Catechol-O-methyltransferase (COMT) is involved in phase II (conjugative) metabolism of catecholamines and catechol drugs,such as dopamine, as well as the catechol-estrogens. COMT transfers a donor methyl-group from S-adenosylmethionine to acceptor hydroxy groups on catechol structures (aromatic ring structures with vicinal hydroxy-groups).(1) Bioactive catecholamine metabolites are metabolized by COMT in conjunction with monoamine oxidase (MAO):

-Norepinephrine is methylated by COMT forming normetanephrine.

-Epinephrine is methylated by COMT forming metanephrine.

-Dopamine is converted to homovanillic acid through the combined action of MAO and COMT.



Parkinsonism patients receiving levodopa (L-DOPA) therapy are frequently also prescribed a COMT inhibitor to minimize metabolism of L-DOPA by COMT, thereby prolonging L-DOPA action.



COMT is also involved in the inactivation of estrogens. Estradiol can be hydroxylated forming the catechol estrogens 2-hydroxyestradiol and 4-hydroxyestradiol.(2) These hydroxylated estradiols are methylated by COMT, forming the corresponding methoxyestradiols. Several studies have
indicated the increased risk of breast cancer due to low activityCOMT.(3)

The gene encoding COMT is transcribed from alternative promoters to produce 2 forms of the enzyme, a soluble short form of the enzyme and a membrane-bound long form. Functional polymorphisms have been identified in the gene encoding COMT that lead to high- and low-activity forms of the enzyme.(4) These functional polymorphisms are designated by the position of the amino acid change in both the short and long form of the enzyme. A single nucleotide polymorphism in exon 4 of the gene produces an amino acid change from valine to methionine (Val108/158Met). This
polymorphism, COMT*2, reduces the maximum activity of the variant enzyme by 25% and also results in significantly less immunoreactive COMT protein, resulting in a 3- to 4-fold decrease in activity compared to wild type *1. A second functional polymorphism has been identified in exon 4 that results in a threonine substitution for alanine (Ala52/102Thr).

This polymorphism, COMT*3, reduces the maximum activity of the variant enzyme by 40% compared to the wild-type enzyme. The COMT*2 polymorphism has been linked to prefrontal cortex cognitive response to antipsychotic medications.

Schizophrenia patients homozygous for the *2 polymorphism displayed improved cognition following drug treatment. Patients homozygous for *1 did not have improved cognition following treatment.(6)

http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/83301

This seems to explain why quninolone based antiobotics are dangerous to a patients with certain variants:

The patient's history lead us to think that the patient was experiencing widespread chronic inflammation. Therefore, we ordered testing to help identify any underlying sources of chronic inflammation. A heavy metal toxicity urine challenge was ordered, along with the following laboratory studies: thyroid panel including thyroid peroxidase and thyroglobulin antibodies to rule out autoimmune hypothyroidism, salivary female hormone panel to evaluate estrogen metabolism, urine porphyrins, urine indican to assess intestinal dysbiosis, complete blood count, Chem 18, and anti-nuclear antibodies (ANA), titer (another autoimmunity screen). In our clinical experience, patients with fibromyalgia often display autoimmune tendencies. Therefore, these labs were ordered to try to identify the xenobiotic, xenoestrogen, or food sensitivities responsible for these autoimmune tendencies. These lab assessments provided the following results: elevated progesterone, low testosterone, elevated coproporhyrin III, elevated total porphyrins, speckled ANA screen (suggestive of autoimmune connective tissue disorder), multiple elevated immunoglobulin G (IgG) titers to dairy-based foods and gluten-based foods, and iron deficient anemia. With these findings, a follow-up genetic detoxification profile was ordered to evaluate the patient's detoxification pathways. This test revealed a genetic polymorphism in the cytochrome P-450 pathway, as well as genetic variations in the catechol-o-methyl transferase enzyme, the Nacetyl transferase enzyme, and the glutathione-s-transferase enzyme necessary for glutathione conjugation and phase II detoxification. These genetic variations may predispose the patient to accumulation of potentially harmful environmental toxins that might otherwise remain subclinical.9 Therefore, the patient was also tested for polychlorinated biphenyls and other volatile solvents. We found the patient to have elevated levels of ethylbenzene, xylene, and the pesticide dichlorodiphenyldichloroethylene. Although these levels could indicate environmental accumulation, impaired detoxification pathways may make this accumulation more of a contributing factor.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981197/


CONCLUSION - PHARMA AND DOCTORS ARE GIVING A LOT OF FOLKS S#IT THAT THEY SHOULDN'T BE GETTING. THIS IS CAUSING A HEALTHCARE CRISIS AND PHARMA AND PRESCRIPTION PROTOCOLS MUST BE TOTALLY RE-ENGINEERED.