Med Biochem Flashcards
(29 cards)
Metabolism of chol to bile salts
- chol is hydrophobic
- adds 1 polar hydroxyl group and 1 carboxyl group on 1 face
- opposite face still hydrophobic
- hydrophilicity increased by conjugation of amino acid glycine or taurine to carboxyl group
- = amphipathic mol
- can form micelles which solubilise chol or emulsify fats
Functions of the liver
- carb metabolism
- protein and aa metabolism (albumin, urea)
- lipid synthesis (lipoproteins)
- bile acid metabolism
- detoxification and excretion (BR, hormones, xenobiotics)
Bile contents
- water
- electrolytes
- bile salts
- phospholipids
- cholesterol
- conjugated BR
What are mixed micelles made of?
- bile salts and phospholipids
Role of mixed micelles in bile
- solubilise chol
- prevent cholesterol precipitation in the gall bladder to form stones
- decrease in bile salts and phospholipids or increase in chol can lead to precipitation
Role of mixed micelles in intestines
- emulsify dietary fats
- aid digestion and absorption of dietary fats
Bile acid enterohepatic circulation
- in liver, chol made into bile salts
- conjugated
- travel to intestine via common bile duct
- deconjugated (5% lost in faeces)
- 95% reabsorbed to liver via portal vein
Definition of xenobiotics
- compounds foreign to the organism
Purpose of xenobiotics metabolism
Transform toxic, non-polar compounds into less toxic, polar metabolites that can be readily excreted by kidneys and in faeces
Process of xenobiotics metabolism
- in phase 1, maj reaction is oxidation
- introduced polar groups to non-polar mol
- in phase 2, metabolite is conjugated to water-sol co-substrate
- increases water solubility in blood and facilitates excretion
Paracetamol metabolism
- normal dose is glucoronidated and excreted as gluceronide
- some sulphated and excreted as sulphate
- only 5% oxidized by cytp450
- generates a reactive electrophilic metabolite which can bind cellular nucleophiles
- electrophile is detoxified by GSH conjugation
- higher dose increases the fraction oxidized by cytp450
- leads to increased need for detoxification by GSH conjugation
- depletion of GSH increases amount of reactive paracetamol metabolites
- cellular toxicity
Explain drug induction
- increased sysnthesis of drug-metabolizing enzymes in response to other drugs
- rapid inactivation
Explain drug inhibition
- inhibition of some drug-metabolizing enzymes by other drugs
- reduced inactivation
Explain allelic variation in drug metabolism
- extensive metabolizers largely excrete drug metabolite
- poor metabolizers largely excrete parent drug (susceptible to drug toxicity)
Structural classification of hormones
- modified aa (epinephrine)
- peptide (insulin)
- steroid (androgens)
Functions of cholesterol in the body
- steroid hormone synthesis
- fat emulsification (as bile salts)
- plasma membr fluidity
Why do aa and peptide hormones bind cell surface receptors
Too large and polar to cross cell membr
Characteristics of hormone action
- tissue specificity
- multi step cascade amplification
- intracellular secondary messengers
- coordinate counter regulation of opposing pathways
- augmentation or opposition by other hormones
Mechanism of testosterone action
- reduced to DHT by 5a-reductase
- HSP dissoc from AR
- AR binds DHT
- dimerised and phosphorylates
- AR binds specific DNA (hormone response element)
- causes target gene activation
Why peptide hormones need cell membr receptors
- amino acids are hydrophilic and polar
- can’t enter cells because plasma membr has hydrophobic lipid bilayer
- must bind cell surface receptors which transmit signal to target
Action of finasteride
- in BHP, increased DHT levels from test in prostate
- DHT binds AR
- leads to activation and transfer to nucleus of target cell
- Activated AR binds promoter regions leading to transcription of genes assoc with proliferation
- increased no of cells exerts press on urethra
- finasteride blocks enzyme that converts test to DHT
- therefore, decreases AR activation, cell prolif
Exogenous lipid pathway
Chylomicrons transport ingested fats to adipose/liver
Endogenous TG pathway
From liver to peripheries
Reverse cholesterol transport
HDL transports chol from peripheral tissues to liver to be excreted as bile
