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Biochem Exam 6

Metabolism of Ethanol

Metabolism of alcohol inthe liver produces Acetate
Ethanol + NAD --> Acetaldehyde + NADH Alcohol dehydrogenase (ADH)
Acetaldehyde + NAD --> Acetate + NADH Acetaldehyde dehydrogenase (ALDH)
Ethanol metabolism occurs mainly in the Liver
Ethanol metabolism oxidizes ethanol to Acetate
Ethanol metabolism reduces NAD+ to NADH
What is the intermediate occuring in ethanol metabolism Acetaldehyde
Two process for convertin gethanol to acetaldehyde exist Alcohol dehydrogenase (ADH) or the MEOS system
With the MEOS system what is not produced NADH
In the case of moderate ethanol consumption, what catalyzes the conversion of ethanol --> acetaldehyde Alcohol dehydrogenase (ADH)
With higher/chronic levels of ethanol consumption, what catabolizes an increasing percentage of the ethanol --> acetaldehyde Microsomal Ethanol Oxidizing System (MEOS)
Where does teh MEOS system occur On the endoplasmic reticulum
What enyzmes is used in the MEOS system Cytochrom P450 enzyme CYP2E1
What is the cytochrome P450 enzyme which oxidizes ethanol to acetaldehyed in the MEOS process CYP2E1
What besides ethonal is oxidized in the MEOS system NADPH
What is used as the ultimate oxidzing agent by cytochrome P450 enzymes Molecular O2
Does CYP2E1 have a higher or lower Km for ethanol than does hepatic ADH Higher
What does ethanol do to other P450 systems Inibits them
The acetate produced from ethanol is activated to Acetyl CoA
Acetyl CoA from Acetate from Ethanol can be used for TCA cycle, Fatty acid synthesis, Cholesterol biosynthesis, Ketone body synthesis
The NADH from ethanol metabolism may be reoxidized via hepatic Oxidative Phosphorylation or Dehydrogenase Reactions
Acetate from ethanol metabolism can be exported from teh liver to extrahepatic cells where it is Activated to acetyl CoA and catabolized via the TCA cycle in these cells
What are three big users of acetate Skeletal muscle, Heart, and Kidney
The ability to metabolize ethanol varies widely from person to person due to the occurrence of Polymorphism inthe enzymes of ethanol metabolism
How many isoenzymes of alcohol dehydrogenase are specific for ethanol Three of five
What isoenzymes of ADH are most specific for ethanol and occur in the liver ADH 1 and ADH 2
Which as the higher Km ADH 1 or ADH 2 ADH 2
Which ADH isoenzyme occurs in the upper GI tract ADH 4
How many isoenzymes of acetaldehyde dehydtrogenas are there Two, ALDH 1 and ALDH 22
Where do the isoenzymes of ALDH occur Liver
Which ALDH isoenzyme is mitochondrial ALDH 2
Which ALDH isoenyzme is cystosolic ALDH 1
What is the major ALDH isoenzyme ALDH 2
Which ALDH isoenzymes has the higher Km ALDH 1
The commone genetic variant of this ALDH isoenzyme has relatively low activity that causes toxic levels of acetaldehyde to accumulate leading to nausea, vomiting, and avoidance of ethanol (homozygotes) ALDH 2
Increased ethanol ingestin results in the induction of the genes for ADH and ALDH
The genes for CYP2E1 are induced in response to Increased ethanol levels
Degradation of CYP2E1 is inhibited by High ethanol levels
NADH levels from high/chronic ethanol ingesting and catabolism may exceed the liver's ability to reoxidize NADH via Oxidative phosphorylation
ADH and ALDH are not regulated b y NADH/NAD or ATP/ADP-AMP levels
The amount of ethanol catabolizm occuring depends on the amount of Ethanol present
Excessive high hepatic NADH levels... TCA Cycle activity Decreases
Isocitrate dehydrogenase is ... by NADH Allosterically inhibited
Excessive high hepatic NADH levels... Beta oxidation Decreases
Excessive high hepatic NADH levels... Glycolysis Decreases
Excessive high hepatic NADH levels... Glycerol-3-phosphate production Increases
Excessive high hepatic NADH levels...Lactate production from pyruvate Increses
Excessive high hepatic NADH levels...Malate prduction from oxaloacetate Increases
A fatty liver may develop because of increased triglyceride synthesis due to Increased glycerol-3-phosphate syntehsis and decreased beta oxidation
Liver damage due to excess acetaldehyde leades to decreased Protein synthesis, Lipoprotein synthesis, Liporotein export
Ketoacidosis may occur with highchronic ethanol ingesting because of Decreased TCA cycle, Excess Acetyl CoA, Increased ketone body production, Decrease ketone body utilization
There is decreased ketone body utilization in high/chronic ethanol ingesting because The heart and kidney prefer to catabolize acetate over ketone bodies
Lactic acidosis may occur with high/chronic ethanol ingestion because High NADH levels increase lactate prduction from pyruvate
At high levels of lactate the liver imports and uses ... amounts of lactate Decreased
Lactate competes with uric acid for excretion by the kidney resulting in Gout
Hypoglycemia in a fast may occur with high/chronic ethanol ingestion because ... hepatic lactate uptake occurs Decreased
A decrease in lactate uptake by the liver cause pyruvate from transamination of alanine to be converted to ... instead of ... Lactate, Glucose
Dihydroxyacetone phosphate is converted to Glycerol=3-phosphate
Hyperglycemia may occur with hihg-chonric ethanol ingetion in a Fed state
Acetaldehyde binds to Amino acids
Acetaldehyde causes ... protein syntehsis Decreased
Lipoprotien syntehsis is decreased due to lack of necessary Apoproteins
Acetaldehyde binds to glutathione decreasing its Antioxidant activity
Increased CYP2E1 activity in the MEOS system ... free radical formation Increases
To correct for hepatic damage the liver attempts wound healing and connetive tissue syntehsis is Increased
What connective tissue is especially used in hepatic repair Collagen
Created by: mhaynes