Alcohol

How many calories in a gram of alcohol?

7kcal

How is alcohol absorbed and transported?

Alcohol is readily absorbed into blood throughout there entire GI tract and is transported unchanged in the circulation

Through what process is alcohol metabolized?

oxidative degradation

Where is alcohol primarily metabolized?

liver

What are the 3 ethanol oxidation systems used to metabolize alcohol and where are they found in the cell?

1. Alcohol dehydrogenase system found in cytosol

2. Microsomal Ethanol Oxidizing System (MEOS) in ER

3. Catalase system in peroxisomes

Describe the alcohol dehydrogenase (ADH) system

ADH is active in the cytosol. The alcohol dehydrogenase enzyme converts ethanol to acetaldehyde, converting NAD+ to NADH in the process.

This is the major pathway in alcohol metabolism

Describe the Microsomal Ethanol Oxidizing System (MEOS)

In the ER, the enzyme CYP2E1 converts ethanol to acetaldehyde. The enzyme also converts NADPH, H+, and O2 to NADP+ and 2H2O

The MEOS system is primarily used in heavy drinkers, when the ADH pathway is already saturated

Explain the catalase system

In the peroxisome, the enzyme catalase converts ethanol and H2O2 to acetaldehyde and H20.

This system plays a relatively minor part in alcohol metabolism and is more prominent in cells that don’t have ADH, like the brain

What is the final product of alcohol oxidation?

acetate

How is acetaldehyde converted to acetate?

Acetaldehyde is transported to the mitochondria, where the enzyme acetaldehyde dehydrogenase (ALDH2) converts acetaldehyde and NAD+ into acetate and NADH

What happens to acetate after alcohol oxidation?

the acetate will be converted to acetyl Co-A and then can be used to create energy in the TCA cycle or stored as fat in fatty acid synthesis

What is H2O2 and why is it dangerous?

H2O2, or hydrogen peroxide is an ROS, or reactive oxidative species, which cause oxidative stress in the body

Why can’t the body leave acetaldehyde in the cell?

Acetaldehyde is a toxin and if it is allowed to build up in the cell it can cause liver damage and inhibits protein function in the cell. Heavy drinkers often have acetaldehyde build up in their cells because their alcohol oxidation systems can’t keep up

How can excess alcohol consumption lead to FA synthesis?

excess acetyl-CoA increases FA synthesis, leading to elevated blood lipid and TG levels and higher risk of fatty liver disease and metabolic syndrome

How does a higher NADH/NAD+ ratio affect the rate of NAD+ and NADH requiring reactions?

The lower amount of NAD+ in the cell reduces the rate of reactions that requiring NAD+, such as gluconeogensis (glucose synthesis), the TCA cycle, and FA oxidation (fat breakdown)

Due to lack of NAD+, the cell will favor reactions that use NADH in order to produce NAD+, such as FA synthesis and lactic acid fermentation

What is lactic acidemia and how can excess alcohol consumption cause it?

Lactic acidemia is the build up of lactic acid in the cells, which can cause muscle pain and fatigue, nausea, and stomach pain.

Excess alcohol consumption requires a high amount of NAD+. However, in order to convert pyruvate to acetyl-CoA and enter the TCA cycle, NAD+ is required. When excess alcohol is consumed, the body can’t convert the pyruvate into Acetyl-Co-A because of the lack of NAD+. Since lactate dehydrogenase converts pyruvate and NADH to lactate and NAD+, the cell favors this pathway and overtime can cause lactic acidemia

What can repeated activation of the MEOS cause?

Since the system can also oxidize Vitamin A, fatty acids, steroids, aromatic hydrocarbons, and some drugs, repeated activation of the MEOS system can accelerate metabolism of these substances. Over time, this can lead to increased need for Vitamin A and can also lead to a tolerance to sedative drugs

Explain the relationship between alcohol and retinol dehydrogenase

Retinol dehydrogenase is the enzyme that converts retinol (the alcohol form of vitamin A) to the active form retinal (the aldehyde form of vitamin A). Since ethanol and retinol have very similar structures, alcohol, when present in excess amounts competitively inhibits retinol dehydrogenase and prevents retinol from binding. This can lead to Vitamin A deficiency (in addition to quicker metabolism of vitamin A from MEOS)

Asian flush syndrome

in some parts of Asia, people have slightly different ADH and ALDH1 enzymes, which causes reduced alcohol tolerance because the enzymes are less efficient

Nutritional Problems related to Alcoholism

poor overall dietary intake can lead to malnutrition

impaired digestion, absorption, and metabolism of some nutrients

increased risk of alcoholic fatty liver disease, cirrhosis, some cancers, CVD, and other metabolic disorders

Wernicke’s encephalopathy

a neurological disorder caused by chronic sever thiamin deficiency; can cause altered mental status, confusion, abnormal eye movement, and gait ataxia within 2 weeks of insufficient thiamine to the brain

Wernicke-Korsakoff syndrome

untreated WE that has caused permanent and irreversible brain damage, memory loss, amnesia, and psychosis

treatment of Wernicke’s Encephalopathy

treat underlying thiamine deficiency, often co-supplemented with folate and magnesium

2025 -2030 DGA recommendations on alcohol consumption

no specific daily limit, but recommends reduced overall alcohol consumption for better overall health

How much ethanol does the standard US drink contain, regardless of beverage type?

14g (0.6oz) of pure ethanol

What were past DGA recommendations for alcohol consumption?

< 1 drink/day for women

< 2 drinks/day for men

What daily intake of ETOH corresponds with a lower risk of CVD, lower BP, and higher HDL?

20g/ day