Lecture 6: Metabolism Flashcards
Blood flow out of the liver
-through hepatic veins into the inferior vena cava
Bile flow out of the liver
-out the bile duct
Oxygen-rich blood flow INTO the liver
through hepatic artery
nutrient rich blood coming from bowel INTO liver
-via portal vein
Bile composition
-water
-bile salts
-bilirubin
-fats
Bile Fuction
-surfactants
-helps fat digestion
-bilirubin elimination
-drug elimination
Bilary excretion into intestine
-gall bladder to cystic duct to duodenum
Hepatic blood flow
1.5 L/min
Liver tissue
-sinusoid w central vein
-portal triad
portal triad
-branch of bile duct
-branch of portal vein
-branch of artery
Blood flow in liver tissue
-from portal triad to center vein
bile flow in liver tissue
-flows out
Kupfer cells
-macrophage cells in liver
-part of reticuloendothelial system
Liver sinusoidal endothelial cells
-make up 15-20% of liver cells
-contain many open pores (fenestrae)
Sinusoidal capillary
-has holes
-allows direct exchange between blood and hepactocytes
Hepatocyte
-synthesis of plasma proteins (albumin, coagulation factors)
-regulation of nutrient balance
-synthesis of bile acids
-detox bilirubin
-detox xenobiotics
-oxireductase-CYP complex in ER
Principles of drug metabolism
- convert lipophilic to hydrophillic
- can be categorized by one of 4 chemical reactions
- Is catalyzed by limited munber of enzymes w broad substrate specificity
- Certain drug-metabolizing enzymes’ expression can be upregulated, leading to inc metabolism of drugs
- Drug metabolism can be inhibited by drugs
- gut microbiota mediate some drug metabolism
Conversion of lipophilic to hydrophilic
-phase 1: functionalization
-phase 2: conjugation
=excretion into bile or urine
Phase 1: functionalization
-adds functional group
Phase 2: conjugation
-attaches hydrophillic group to functional group
- chemical reactions of drug metabolism
- oxidation
- conjugation
- Hydrolysis
- Reduction
Oxidation
-add -OH
-usually followed by conjugation
Hydrolysis
-cleave
Reducation
=O to -O
