Term
Chronic Consumption of Ethanol
Steps (3) |
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Definition
Leads to liver cirrhosis
Ethanol causes a fatty liver
Fatty liver results in alcoholic hepatitis
Hepatitis leads to cirrhosis |
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Term
| Result of Cirrhotic liver (2) |
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Definition
Portal hypertension
Esophageal varices |
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Term
| Cirrhosis accounts for what percentage of deaths |
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Definition
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Term
| Toxic effect of ethanol on fetus |
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Definition
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Term
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Definition
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Term
| What vitamin does alcohol effect? (3) |
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Definition
Thiamine mainly
Folic Acid
B12 |
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Term
Over 80% of ethanol metabolism occurs here
Describe the pathway (2) |
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Definition
Liver
Constitutive and unregulated |
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Term
| 2 Steps of Ethanol Metabolism |
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Definition
Ethanol oxidized to acetaldehyde using NAD+ in cytosol
Acetaldehyde is oxidized to acetate in mitochondria using NAD+ |
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Term
Step 1 Ethanol Metabolism Enzyme
Number of genes? Which ones?
Special genetic feature
Location |
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Definition
Cytosolic Alcohol Dehydrogenase
3
ADH1, ADH2, ADH3
Polymorphic
Cytosol |
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Term
Km of ADH for ethanol
Result |
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Definition
Below levels of alcohol achieved with moderate drinking.
Easily saturated |
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Term
Step 2 Ethanol Metabolism enzyme
Main form?
Location
Other function |
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Definition
Aldehyde Dehyrogenase
ALDH2
Mitochondria
Release of NO from nitroglycerin |
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Term
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Definition
| Vasodilator used to relieve pain of angina |
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Term
| Acetate produced from ALDH (2) |
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Definition
Sent to other tissues like muscle for conversion to Acetyl CoA using ATP.
Acetyl CoA produced sent to TCA |
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Term
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Definition
| Inducible form of CYP2E1 in the ER |
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Term
CYP2E1 inducibility
Result |
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Definition
5-10 fold
Increases tolerance |
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Term
| In frequent drinkers, what percentage of ethanol metabolism is CYP2E1? |
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Definition
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Term
Does CYP2E1 have a high or low Km for Ethanol?
Result? |
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Definition
high: 11 mM
Active at higher ethanol concentrations |
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Term
| CYP2E1, Ethanol and Other Drugs (2) |
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Definition
1. Alcoholics may be more tolerant of certain drugs due to quick CYP2E1 metabolism
2. Competition with CYP2E1 results in decreased drug tolerance. |
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Term
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Definition
Induction
Enzyme has been turned on by something else so drug is metabolized quicker |
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Term
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Definition
| Enzyme is being competed by something else and the drug so that the drug lasts longer in the body. |
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Term
| ATP production from ADH conversion of ethanol to acetaldehyde |
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Definition
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Term
| ATP production from CYP2E1 conversion of ethanol to acetaldehyde |
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Definition
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Term
| Two main acute effects of alcohol |
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Definition
1. High NADH in cytoplasm inhibits gluconeogenesis from lactate or glycerol
2. High NADH in mitochondria inhibits rate limiting steps of TCA and shifts malate/oxaloacetate rxn to malate. |
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Term
| High Malate/Oxaloacetate ratio (2) |
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Definition
Decreased gluconeogenesis from oxaloacetate
Increased ketogenesis in liver due to decreased OAA. |
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Term
| 7 Chronic effects of alcohol |
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Definition
1. Ethanol oxidation replaces fat as main fuel in liver
2. Easier for other conditions to lead to fatty liver.
3. Toxic acetaldehyde
4. Hepato-encephalopathy
5. Vitamin absorption such as thymine
6. AST > ALT
7. Macrocytosis |
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Term
| FA's destination in chronic ethanol liver |
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Definition
| Stored as TAG's or VLDL resulting in fatty liver |
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Term
| Chronic alcohol liver conditions that can add to fatty liver (2) |
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Definition
1. Lack of protein or AA's (can't make VLDL)
2. Lack of choline (Can't make VLDL) |
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Term
| 3 Examples of increased Triglyceride synthesis |
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Definition
Starvation
Diabetes mellitus
Alcoholism |
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Term
| How starvation increases TG synthesis |
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Definition
| Increased FA's from adipose |
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Term
| 3 examples of decreased formation of VLDL |
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Definition
Protein deficiency
Essential FA deficiency
Toxic liver damage |
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Term
| How diabetes mellitus increases TG synthesis |
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Definition
| Increased FA's from adipose |
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Term
| How alcoholism leads to increased TG synthesis |
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Definition
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Term
| How protein deficiency decreases VLDL |
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Definition
| Decrease synthesis of VLDL apolipoprotein |
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Term
| How essential FA deficiency leads to decreased VLDL |
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Definition
| Decreased phospholipid synthesis |
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Term
| How toxic liver damage leads to decreased VLDL |
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Definition
| VLDL formation is impaired greater than TG synthesis |
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Term
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Definition
Toxic
Reacts with free amino groups |
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Term
| Liver Cirrohosis Abnormalities and impaired function(3) |
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Definition
Fasting Hypoglycemia - Glycogenolysis and Gluconeogenesis
Prolonged clotting - synthesis of CF's
Jaundice - Bilirubin metabolism |
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Term
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Definition
| Decreased liver function results in decreased detoxification of xenobiotics and drugs leading to toxification of brian. |
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Term
| AST:ALT ratio in alcoholism |
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Definition
| AST/ALT ratio is 2:1 or more |
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Term
| Result of increased NADH from alcohol? (4) |
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Definition
Increases lactate
Ketogenesis
Fatty liver
Inhibits gluconeogenesis |
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Term
| Why large anion gap in acute alcoholic (2) |
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Definition
Ketone bodies due to low OAA
Maybe lactate |
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Term
| pH of acute alcoholic attack |
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Definition
| Low due to ketone bodies and lactate |
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