Metabolism: Liver Metabolism Flashcards
What is cytochrome p450?
superfamily of enzymes used in drug metabolism
- oxidizes drugs and organic metabolites
What is the requirement for drug excretion via the kidney?
drug must be hydrophilic
In general, describe the metabolism of a drug by cytochrome p450.
- NADPH => NADP via NADPH-cytochrome-p450-reductase
- electron added to drug-cytochrome complex
- drug is now reduced
- add O2, H
- drug is now oxidized
- drug and cytochrome separate
- oxidized drug includes OH/COOH (hydrophilic components)
Under what conditions do drug metabolism enzymes have decreased activity?
- newborns
- elderly
- undernutrition
Under what conditions do drug metabolism enzymes have increased activity?
- smoke induces polyclyclic aromatic hydrocarbons
What is the purpose of phase 2 drug metabolism reactions?
conjugate oxidized drug products to make them more hydrophilic
- ex: glucuronate, glycine, taurine, sulfate
What is the purpose of plasma proteins?
- plasma oncotic pressure maintenance
- conjugation of bilirubin
- FA transport
How is vitamin A transported to the liver?
- exists as retinol esters in chylomicrons
- LPLs breakdown chylomicrons to chylomicron remnants
- delivered to liver
How does the liver maintain vitamin A homeostasis?
- breaks down stored retinyl esters to retinol
- association with retinol-binding-protein (RBP)
- released into circulation
How much vitamin A is stored?
80% stored in liver
How is vitamin D transported?
- chylomicrons
- vitamin D3 (nonesterified calcitriol)
Where are vitamin D stores found?
adipose
skeletal muscle
What is the liver’s role in vitamin D metabolism?
- activates D3 via hydroxylation => 25-hydroxycholecalciferol
- synthesizes vitamin-D binding protein (DBP) which binds to D3
Where is vitamin K found in the body?
- stored in skeletal muscle
- required in liver for prothrombin synthesis
List the steps to make the stored form of iron.
- dietary iron binds to transferrin protein transporter
- transferrin-Fe binds to transferrin receptor on liver and is endocytosed
- heme oxygenase breaks down to release free iron into the free iron pool
- iron stimulates synthesis of ferritin (stored form)
What is the free iron pool in the liver used for?
- synthesis of apotransferrin protein
- synthesis of transferrin
- ferritin
What are the sources of the iron pool?
- heme degradation
- dietary Fe
What is the liver’s role in copper metabolism?
- storage
- excretion in bile
List the hormones that liver metabolism is involved with.
- D3
- thryoid
- IGF
Describe the liver’s role in D3 activation.
takes D3 and hydroxylates it
Describe the liver’s role in thyroid hormone activation.
converts T4 to T3
Describe the liver’s role in IGF hormone activation.
- synthesis of Insulin-like Growth Factor
- stimulated by somatotropin
