Liver Alcohol Dehydrogenase: An Equal Opportunity Detoxifier of Organic Compounds, Toxins and Pollutants

1. Liver Alcohol Dehydrogenase: An Equal Opportunity Detoxifier of Organic Compounds, Toxins and Pollutants A metal cation lowers the pKa of water coordinately bound to the metal ion providing a source of OH-. Ethanol Acetaldehyde Acetic Acid

2. Water originally coordinately bound to • the metal ion has been replaced by the ethanol. The alcohol functional group has been deprotonated by the readily available OH-. • NAD+/NADH is not coordinately bound but resides in the catalytic pocket. • (Nicotinamide Adenine Dinucleotide, vitamin B3, is one of the most important coenzymes in the human brain and body. A coenzyme is the active, or working form of a vitamin.  NADH is the reduced (electron- energy rich) coenzyme form of vitamin B3, while NAD is the oxidized (burned) coenzyme form of B3) • NAD+ closes the pocket • NADH opens the catalytic pocket. • The catalytic pocket Zn2+ ions serves two purposes • to deprotonate the alcohol • to position the alcoholate near the enzyme cofactor for hydrid transfer “Principles of Bioinorganic Chemistry”, Lippard and Berg, University Science Books, Mill Valley, CA, 1994

3. ~ Properties of Ethanol & its toxicity ~ Ethanol is a monohydric primary alcohol. It boils at 78.5° C. It is miscible (i.e., mixes without separation) with water in all proportions and is separated from water only with difficulty; Ethanol forms a constant-boiling mixture, or azeotrope, with water that contains 95% Ethanol and 5% water and that boils at 78.15° C; since the boiling point of this binary azeotrope is below that of pure Ethanol, absolute Ethanol cannot be obtained by simple distillation. Clinical Effects of Ethanol: The effects of moderate alcohol consumption is well known to most people. Patients present with dis-coordination, and slurred speech. At high doses Ethanol is a general CNS depressant. Alcohol is broken down in the liver by alcohol dehydrogenase. Medically, Ethanol is a soporific, i.e., sleep-producing; although it is less toxic than the other alcohols, death usually occurs if the concentration of Ethanol in the bloodstream exceeds about 5%. Behavioural changes, impairment of vision, or unconsciousness occur at lower concentrations. With levels as low as 50-100 mg/dl children can present with coma, hypothermia, and hypoglycaemia. ~ Methanol & its toxicity ~ Methanol itself may cause inebriation but by itself is almost completely non-toxic. The problem you see is methanol is metabolized by liver alcohol dehydrogenase also; to formaldehyde then to formic acid. It is these two metabolites that cause toxicity, with formic acid being more responsible. It is the formic acid that causes the profound metabolic acidosis that is typical of Methanol poisoning. The overall mortality of Methanol poisoning is approximately 20% and among survivors the rate of permanent visual impairment is 20-25%. Fatal dose 100ml. Poisoning with Methanol may be accidental or intentional. There have been epidemics of Methanol toxicity in cases where illicit whiskey has been sold to large populations or when the less expensive Methanol was substituted for Ethanol in drinks. Ethanol is used to decrease the metabolism of Methanol. Alcohol dehydrogenase acts to break down both Ethanol and Methanol, and is the rate limiting step in the metabolism. The enzyme, alcohol dehydrogenase, has a greater affinity for Ethanol than it does for Methanol. Therefore, in the presence of Ethanol, the metabolism of Methanol to its toxic metabolites is greatly slowed. It is appropriate to begin an Ethanol drip while awaiting blood levels of Methanol. Ethanol drips are also indicated if the blood Methanol level returns and is 20 mg/dl or above. The target Ethanol level is 100-150 mg/dl since this is the level that will saturate alcohol dehydrogenase.

4. The degree of toxicity correlates with the amount of methanol ingested, but not with presenting methanol levels. Latency between ingestion and toxicity occurs because of the time required to convert methanol to toxic metabolites. The toxic effects become apparent when LADH has metabolized methanol to formaldehyde. Formaldehyde is highly toxic but is rapidly degraded by aldehyde dehydrogenase and other nonspecific enzymes to formic acid, which is responsible for the metabolic acidosis and anion gap. Further metabolism of formic acid to carbon dioxide is dependent on folate.

5. Aspartame Kills!

6. Holistic Medicince.com states: Abuse of the Scientific Method Seen in Monsanto Aspartame Research in Collusion with the FDA and the Multiple Sclerosis Society Subject: FW: Health information on ASPARTAME WORLD ENVIRONMENTAL CONFERENCE and the MULTIPLE SCLEROSIS FOUNDATION F.D.A. ISSUING FOR COLLUSION WITH MONSANTO Article written by Nancy Markle (1120197) I have spent several days lecturing at the WORLD ENVIRONMENTAL CONFERENCE on "ASPARTAME marketed as 'NutraSweet', 'Equal', and 'Spoonful"'. In the keynote address by the EPA, they announced that there was an epidemic of multiple sclerosis and systemic lupus, and they did not understand what toxin was causing this to be rampant across the United States. I explained that I was there to lecture on exactly that subject. When the temperature of Aspartame exceeds 86 degrees F, the wood alcohol in ASPARTAME coverts to formaldehyde and then to formic acid, which in turn causes metabolic acidosis. (Formic acid is the poison found in the sting of fire ants). The methanol toxicity mimics multiple sclerosis; thus people were being diagnosed with having multiple sclerosis in error. The multiple sclerosis is not a death sentence, where methanol toxicity is.

7. Toxicity Effects of Aspartame Use Selection of adverse effects from short-term and/or long-Term use seizures and convulsions dizziness tremors migraines and severe headaches (Trigger or Cause From Chronic Intake) memory loss (common toxicity effects) slurring of speech confusion numbness or tingling of extremities chronic fatigue depression insomnia irritability panic attacks (common aspartame toxicity reaction) marked personality changes phobias rapid heart beat, tachycardia (another frequent reaction) asthma chest pains hypertension (high blood pressure) nausea or vomitting diarrhea abdominal pain swallowing pain itching hives / urticaria other allergic reactions blood sugar control problems (e.g., hypoglycemia or hyperglycemia) menstrual cramps and other menstraul problems or changes impotency and sexual problems food cravings weight gain hair loss / baldness or thinning of hair burning urination & other urination problems excessive thirst or excessive hunger bloating, edema (fluid retention) infection susceptibility joint pain brain cancer (Pre-approval studies in animals) death Aspartame Disease Mimmicks Symptoms or Worsens the Following Diseases fibromyalgia arthritis multiple sclerosis (MS) parkinson's disease lupus diabetes and diabetic Complications epilepsy alzheimer's disease birth defects chronic fatigue syndrome multiple chemical sensitivities (MCS) lymphoma lyme disease attention deficit disorder (ADD and ADHD) panic disorder depression and other psychological disorders

8. Urban Legends and Folklore • From David Emery,Your Guide to Urban Legends and Folklore. • This is a hoax: http://urbanlegends.about.com/library/blasp.htm • The Laundry List http://urbanlegends.about.com/library/blasp2.htm • The “Mis”information http://urbanlegends.about.com/library/blasp3.htm • The methyl group is popped off in the small intestine by chymotrypsin, and then follows the pathway to methanol, formaldyhde, formic acid, and finally is converted from formate to carbon dioxide and water. Methyl groups are ubiquitous. Chymostrypsin can do the same thing to the results from the digestion of apples and oranges. This much is true. But does drinking soda pop artificially sweetened with Aspartame result in poisoning? • Is the data about Splenda or Soy Protein sweeping the Internet any more reliable?