ethanol metabolism

Question 1

What is the major route of ethanol metabolism in the body?

Answer 1

Ethanol is metabolized primarily in the liver.

Question 2

Reaction catalyzed by alcohol dehydrogenase

Answer 2

occurs in the cytosol, ethanol is oxidized to aldehyde/acetaldehyde. some. uses NAD+ as the oxidizing agent. zinc is a cofactor /

Question 3

what is the oxidizing agent in the alcohol dehydrogenase

Answer 3

NAD+

Question 4

what cofactor is required in the alcohol dehydrogenase reaction and what is the charge/ does it change?

Answer 4

zinc, +2. no, does not change charge.

Question 5

describe the acetaldehyde dehydrogenase reaction.

Answer 5

occurs in the mitochondrial matrix. oxidized to carboxylic acid form. NAD+ is the oxidizing agent. produces a lot of NADH.

Question 6

what is the product of the acetaldehyde dehydrogenase version? how is it used?

Answer 6

acetate, and its exported and used by muscle cells who attach coenzyme A to make it useful

Question 7

Describe the acetyl coA synthetase reaction and where it is located.

Answer 7

muscle cells have it, attach coenzyme A. requires ATP. mitochondrial matrix.

Question 8

where does acetyl coA go next after acetyl coA synthetase reaction?

Answer 8

it is oxidized further via the electron transport chain. makes ATP. skeletal muscle and heart muscle have this enzyme.

Question 9

describe the Microsomal ethanol oxidizing system (MEOS)

Answer 9

occurs in endoplasmic reticulum. oxidizing agent is oxygen (o2) and reducing agent is NADPH.

Question 10

what cytochrome p450 enzyme is associated with MEOS

Answer 10

CYP2E1

Question 11

what percent of alcohol oxidation occurs with MEOS vs. alcohol dehydrogenase

Answer 11

10–20% MEOS and 80-90% alcohol dehydrogenase

Question 12

What are the acute effects of ethanol metabolism on the body?

Answer 12

Ethanol metabolism results in an increased NADH/NAD+ ratio in liver cells, leading to hyperlipidemia, hepatic steatosis, ketoacidosis, lactic acidosis, hyperuricemia, and hypoglycemia.

Question 13

Describe hyperlipidemia from acute alcohol intake.

Answer 13

Beta oxidation is inhibited by NADH in mitochondrial matrix..Liver in a mode to produce fatty acids and fats rather than use them as fuel. Package those into vLDL into the blood/hyperlipidemia. Problem with packaging vLDL (fatty liver/fats stay in liver).

Fatty acyl transferase / fatty acyl groups to glycerol backbones, inducible/ etoh on regular increases these.

Question 14

dehydration

Answer 14

body’s attempt to get rid of lactate, urate, ketone bodies - lose water. Ethanol makes it more difficult for posterior pituitary to relate ADH.

Question 15

ketoacidosis

Answer 15

cause lowering of pH in blood stream. Why so many ketones? NADH. Lots of NADH, forces malate dehydrogenase reaction in direction that uses NADH. oxaloacetates difficult to find. Acetyl coA increase, ketogenesis. Acidosis: lactate - lactate dehydrogenase from pyruvate (likely to be reduced).

Question 16

uric acid/alcohol intake

Answer 16

lactate and urate compete for same process out of body. Tubular secretion. Things put into urine. Lactage/uric excreted same. When more lactate, makes it harder for body to get rid of urate, can increase crystals in joint.

Question 17

hypoglycemia

Answer 17

ajor precursor: lactate… not becoming lactate (NADH), impaired. Alanine becomes pyruvate just fine, but to continue using alanine, doesn’t go further because pyruvate gets reduced to lactate and doesn’t be made into glucose. Glycerol (glycerol 3 phosphate just fine, but next step for gluconeogensis doesn’t happen). Gluconeogensis isn’t working well because of NADH, all the precursors aren’t going gluconeogenesis direction.

Question 18

describe the role of acetaldehyde in development of ethanol induced hepatitis

Answer 18

Acetaldehyde binds to nitrogens, glutathione, amino acids, proteins, microtubules, and impaired how well those work.

To protect cell, cell needs reduced glutathione. When acetaldehyde binds, makes a Schiff based adduct in glutathione. Doesn’t work as well with alcohol.

Cycle of toxicity. Liver makes all the important blood proteins (clotting factors, albumin) now having trouble because have acetaldehyde attached Schiff base duct… makes secretion of proteins difficult, not made or exported like normal.

Impair secretion of vLDLs - build up of fat inside liver cells/ fatty liver.

Question 19

describe which liver enzymes are elevated and why

Answer 19

Membrane has been damaged via lipid per oxidation - water enters (osmotically) cell swells, damage membrane allows release of liver enzymes - indication of liver damage. ALT/AST in blood stream.

Question 20

describe effects of cirrhosis on liver.

Answer 20

Fatty liver —> fibrosis and beyond

Hepatocyte damaged from acetaldehyde (all the Schiff base/cycle of toxicity/MEOS)

Debris from damaged liver cells, activates resident macrophages Kupffer cells. Now activated Kupffer cell (Transforming growth factor beta OR respiratory burst ROS/NO) —> stellate cells - perisinusoidal /Ito cells (body stores vitamin A) —> stimulated stellate cell —> begin making collagen/fibrosis

Question 21

effects of cirrhosis with albumin

Answer 21

edema (ascites) occurs in abdominal cavity, worsened by portal hypertension

Question 22

glycogenoloysis and gluconeogenesis

Answer 22

fasting hypoglycemia

Question 23

synthesis of clotting factors

Answer 23

risk of serious bleeding

Question 24

conjugation and excretion of bilirubin

Answer 24

jaundice icteric sclerae

Question 25

urea cycle

Answer 25

hyperammonia, hepatic encephalopathy

Question 26

portal hypertension

Answer 26

blood flow through sinusoids impaired, anastomoses form between veins of portal circulation and systemic circulation, when they mix, the BP in the hepatic portal goes way up. Causes varicose vein’s in places of portal circulation. Lower esophagus. Superficial, thin walled, dilated by high bP inside. Bleeding happen here, no clotting factors, bleed to death.