A short presentation of the relation between the metabolic pathways of Alcohol metabolism and its role in the features of toxicity in humans.

1. Metabolism & Toxicity

4. Metabolism
Environmental
Genetic Variations

5. the rate of alcohol drinking
the presence of food in the stomach
the type of alcoholic beverage
(Beer/Rum/Whisky)
genetic factors (variations in the principal alcohol-
metabolizing enzymes)
Blood Alcohol Concentration (BAC)
Decides the effects of Alcohol on various tissues.
BAC
Depends
on

6. Stomach 20%
Small Intestine 80%
First pass metabolism
Elimination rate: 15mg/dl/hr

7. The alcohol elimination rate varies widely (i.e., three-fold)
among individuals.
Bennion and Li 1976; Kopun and Propping 1977
Influenced by factors:
chronic alcohol consumption
diet
age
Smoking .

8. Interactions with
metabolic pathways
Elimination of Alcohol
& Toxic Metabolites

10. Samir Zakhari, Alcohol Research & Health, 2009

11. Acetaldehyde
Protein
Adducts
DNA
Adducts
Neuro-
transmitter
Adducts
Salsolinol
1-N2, Propane deoxy guanosine

12. Acetate:
Acetyl CoA – Lipid & Cholesterol Biosynthesis
Increase blood flow to liver.

14. Increased NADH/NAD+ ratio
• Hypoxic state in the cell – Lactic Acidosis
• Highly reduced cytosolic environment.
• Hypoglycemia – Due to inhibition of Gluconeogenesis.
ADH & ALDH involved in Retinol & Retinoic Acid
Metabolism.
Fetal Alcohol Syndrome.

15. www.medicalbiochemistrypage.org
Liver damage,
Hepatocellular Carcinoma
Fetal Alcohol Syndrome
Microsomal Ethanol Oxidizing System (MEOS)

16. PORTER:
Drinking turns your nose red (Vasodilatation), it puts you to
sleep (CNS depression), and it makes you urinate (Inhibits
secretion of Vasopressin). Sir, it provokes and unprovokes. It
provokes the desire, but it takes away the performance. It
persuades you and discourages you.
Shakespeare, Macbeth, Act 2, Scene 2
MACDUFF:
What three things does
drink make a man do?

17. Acute Alcohol Intoxication:
80mg/dl: Slurred speech, incoordination, Unsteady gait.
80 -200mg/dl: Cognitive effects, Aggressiveness, Amnesia.
>200mg/dl: Nystagmus, Coma, Death.
Legal limits: 30mg/100mL.

19. Genetic Variations:
ADH1B2: Jews
ADH1B3: African Americans
Faster Metabolism.- Elevated Aldehyde levels- Reduced
Alcohol intake.
Indians: ADH1B1. No ADH1B3
ALDH2*2: Elevated Aldehyde Levels- Reduced
Alcohol Intake.

20. Methanol
Country Liquor (Arrack, Hooch, Bootleg)
Paint Thinner
Anti freeze in Automobiles
Laboratory chemical
Food contaminants

21. Methanol
Toxic Dose: 20mg/dl.
Lethal Dose : 300-1000mg/dl
Methanol
Optic Nerve
Injury

22. Ocular
Toxicity &
Death
Metabolic
Acidosis
CNS
Depression
Methanol Poisoning
Poison Information Monograph, WHO, 2007

23. Treatment of Methanol Poisoning
Maintenance of Airway, Breathing, Circulation.
I.V., Sodium Bicarbonate for acidosis.
Ethanol i.v., - a competitive inhibitor of Alcohol
Dehydrogenase.
4- Methyl Pyrazole – a competitive inhibitor of Alcohol
Dehydrogenase.
Folate to metabolize and eliminate Formic acid.
Hemodialysis.

24. Further Reading:
• Goodman & Gilman, The Pharmacological Basis of
Therapeutics, edn 12th.
• Overview: How is Alcohol metabolized by the body?-
Samir Zakhari, Alcohol Research and Health.

25. Thank you