Transcript Slide 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
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the metal ion has been replaced by the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
~ 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 constantboiling 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.
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.
Aspartame Kills!
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.
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
lymphoma
epilepsy
lyme disease
alzheimer's disease
attention deficit disorder (ADD and ADHD)
birth defects
panic disorder
chronic fatigue syndrome
depression and other psychological disorders
multiple chemical sensitivities (MCS)
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?