1. ALCOHOL METABOLISM
Break Down and Removal

2. Alcohol consumption and Health
Alcohol is the most favourite mood-altering drug
Effects are both pleasant and unpleasant
alcohol is a toxic drug that produces pathological changes (cirrhosis) in liver tissue and can cause death.

3. readily absorbed from the gastrointestinal tract
cannot be stored and therefore, the body must oxidize it to get rid of it.
Alcohol can only be oxidized in the liver, where enzymes are found to initiate the process.

4. Small Amounts Unmetabolized (10%)
Most of the alcohol consumed is metabolized in the liver, but the small quantity that remains unmetabolized permits alcohol concentration to be measured in breath and urine.
Sweat
Urine
Breath

5. 1st Pass Metabolism Occurs in the Stomach
Gender Differences Exist: Men have a higher level of ADH than women
Early metabolism translates to lower BAC levels

6. 2nd Pass Metabolism Occurs in the Liver
1st liver enzyme--Alcohol Dehydrogenase (ADH)--- --> Acetaldehyde
2nd liver enzyme--Acetaldehyde Dehydrogenase-- --> Acetic Acid
Acetic Acid oxidized by body organs----> CO2 + H2O

7. Cellular metabolism of alcohol
2019/1/18
Cellular metabolism of alcohol
EtOH
Cytosol
ADH
NAD+
NADH
Acetaldehyde
Mitochondrion
ALDH
NAD+
NADH
Acetate
EtOH: ethanol
ADH: alcohol dehydrogenase; genetic polymorphisms lower response to EtOH
NAD+/NADH: nicotinamide adenine dinucleotide
CAT: catalase
MEOS: microsomal ethanol-oxidizing system
P450: cytochrome P450
NADP+/NADPH: nicotinamide adenine dinucleotide phosphate
AlDH: aldehyde dehydrogenase; ~50% ethnic Chinese lack gene
Thiamine is consumed during hepatic metabolism of EtOH, hypothalamus responds to thiamine deficiency by ordering increase in hepatic ADH activity that gives enhanced EtOH degradation.

8. Metabolism of alcohol
A number of metabolic effects from alcohol are directly linked to the production of an excess of acetaldehyde.

9. Toxicity of acetaldehyde
acetaldehyde exerts its toxic effects by inhibiting the mitochondria reactions and functions.
a vicious circle: a high acetaldehyde level impairs mitochondria function, metabolism of acetaldehyde to acetic acid decreases, more acetaldehyde accumulates, and causes further liver damage:
hepatitis and cirrhosis.

10. Factors affecting Absorption & Metabolism
Food. The rate at which alcohol is absorbed depends on how quickly the stomach empties its contents into the intestine. Explain why fatty foods delay alcohol absorption.
Gender. Women have higher BAC's after consuming the same amount of alcohol as men. Explain.

11. Factors affecting Absorption & Metabolism
Food. The rate at which alcohol is absorbed depends on how quickly the stomach empties its contents into the intestine. Explain why fatty foods delay alcohol absorption.
Gender. Women have higher BAC's after consuming the same amount of alcohol as men. Explain.
The higher the dietary fat content, the more time food stay in stomach and the slower the process of absorption will take place.
This is attributed to women's smaller amount of body water, thus a higher BAC for the same amount of alcohol absorbed in women than in man. . An additional factor may be that women have lower activity of the alcohol metabolizing enzyme ADH in stomach.

12. Blood Alcohol Concentration
The ratio of alcohol in blood to the total volume of blood as a percentage
THE PERSUMPTIVE LEVEL OF INTOXICATION = 0.10%

13. BAC--Blood alcohol concentration
Blood alcohol concentration (BAC) after the rapid consumption of different amounts of alcohol by eight adult fasting male subjects
The statutory limit of alcohol concentration in driver is 80 mg of alcohol in 100 ml of blood in the UK.

14. Blood Alcohol Conc. and Effects
BAC
# Drinks Consumed
Effects
Hours needed to metabolize alcohol
.05
1-2
relaxation; decreased inhibition and judgment; decreased reaction time and alertness
2-3
3-4
marked decrease in fine motor skills, reaction time, and judgment; may be clumsy; exaggerated behaviors
4-6
5-7
vision and perception affected; can be verbally argumentative, emotionally irrational; further impairments in reaction time and judgment
6-10
8-10
staggering; slurred speech; blurred vision; sensory and motor skills greatly affected; nausea/vomiting
10-24
more than 0.30
more than 10
stuporous; may be conscious but unaware of surroundings; decreased respiration; anesthesia at levels above 0.35; approximately 50% will die at levels above 0.40
more than 24

15. Eyes: �    impaired visual acuity, distorted vision Throat (1): �    irritates and damages esophagus �    induces vomiting,  may eventually cause cancer Heart (4): �    weakens the heart,
�    increases blood pressure, increased risk of heart attack
Lungs: �    high amounts may cause breathing to stop, then death Stomach (2): �    irritation of stomach lining, peptic ulcers, inflammation, bleeding lesions and cancer Intestines: (3) �    irritates lining, resulting in nausea, vomiting, diarrhea,. �    inhibits nutrients and vitamins processing
Liver (5): �    causes fat accumulation around liver �    leads to its inflammation and destruction of cells (hepatitis) �    results in lesions and scarring, along with cirrhosis
Reproductive: �    decreases testosterone �    increases sexual desire, but decreases sexual performance

16. Alcohol’s effects on the body
Malnutrition
High energy content but…
Low nutritive value: ethanol does not have any minerals, vitamins, carbohydrates, fats or protein associated with it.
Alcohol causes inflammation of the stomach, pancreas, and intestines which impairs the digestion of food and absorption into blood.

17. Hepatic Complications of Alcohol
Fatty Liver
Alcoholic Hepatitis
Cirrhosis
Cancer

18. A polymorphism
Some people have an alteration in the ALDH gene, called a polymorphism, that makes it slow to convert acetaldehyde into acetic acid. What is your recommendation to those who have this deficiency?

19. A polymorphism
Some people have an alteration in the ALDH gene, called a polymorphism, that makes it slow to convert acetaldehyde into acetic acid. What is your recommendation to those who have this deficiency?
They will have slower elimination of alcohol, and accumulation of acetaldehyde in the blood causes more severe toxic effects –hangover, in body. For someone who have this deficiency, they should avoid alcohol.

20. One Gene Variant Leads to Higher Brain Acetaldehyde
Alcohol Acetaldehyde Acetate
ALDH 2-1
Alcohol ACETALDEHYDE Acetate
ALDH 2-2
~ 50% of Asians (Japanese, Chinese, Korean) have the ALDH2-2 version of ALDH, a slow- working version.
Would you expect higher or lower rate of alcoholism of Asians compare to Caucasians?

21. One Gene Variant Leads to Higher Brain Acetaldehyde
Alcohol Acetaldehyde Acetate
ALDH 2-1
Alcohol ACETALDEHYDE Acetate
ALDH 2-2
~ 50% of Asians (Japanese, Chinese, Korean) have the ALDH2-2 version of ALDH, a slow- working version.
Asians have much lower rates of alcoholism.

22. DISULFIRAM (Antabuse®)
Inhibits aldehyde dehydrogenase activity
Leads to increased acetaldehyde after drinking alcohol.
Suggest one practical use of (Antabuse®)

23. DISULFIRAM (Antabuse®)
Inhibits aldehyde dehydrogenase activity
Leads to increased acetaldehyde after drinking alcohol.
Suggest one practical use of (Antabuse®)
Antabuse can help some quit drinking.

24. Psycho-Social Complications
Drink driving convictions
Domestic violence
Impaired work/loss of job
Accidents
Marriage breakdown
Depression