Med Biochem

Question 0

Metabolism of chol to bile salts

Answer 0

• 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

Question 1

Functions of the liver

Answer 1

• carb metabolism
• protein and aa metabolism (albumin, urea)
• lipid synthesis (lipoproteins)
• bile acid metabolism
• detoxification and excretion (BR, hormones, xenobiotics)

Question 2

Bile contents

Answer 2

• water
• electrolytes
• bile salts
• phospholipids
• cholesterol
• conjugated BR

Question 3

What are mixed micelles made of?

Answer 3

• bile salts and phospholipids

Question 4

Role of mixed micelles in bile

Answer 4

• 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

Question 5

Role of mixed micelles in intestines

Answer 5

• emulsify dietary fats

- aid digestion and absorption of dietary fats

Question 6

Bile acid enterohepatic circulation

Answer 6

• 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

Question 7

Definition of xenobiotics

Answer 7

• compounds foreign to the organism

Question 8

Purpose of xenobiotics metabolism

Answer 8

Transform toxic, non-polar compounds into less toxic, polar metabolites that can be readily excreted by kidneys and in faeces

Question 9

Process of xenobiotics metabolism

Answer 9

• 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

Question 10

Paracetamol metabolism

Answer 10

• 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

Question 11

Explain drug induction

Answer 11

• increased sysnthesis of drug-metabolizing enzymes in response to other drugs
• rapid inactivation

Question 12

Explain drug inhibition

Answer 12

• inhibition of some drug-metabolizing enzymes by other drugs
• reduced inactivation

Question 13

Explain allelic variation in drug metabolism

Answer 13

• extensive metabolizers largely excrete drug metabolite

- poor metabolizers largely excrete parent drug (susceptible to drug toxicity)

Question 14

Structural classification of hormones

Answer 14

• modified aa (epinephrine)
• peptide (insulin)
• steroid (androgens)

Question 15

Functions of cholesterol in the body

Answer 15

• steroid hormone synthesis
• fat emulsification (as bile salts)
• plasma membr fluidity

Question 16

Why do aa and peptide hormones bind cell surface receptors

Answer 16

Too large and polar to cross cell membr

Question 17

Characteristics of hormone action

Answer 17

• tissue specificity
• multi step cascade amplification
• intracellular secondary messengers
• coordinate counter regulation of opposing pathways
• augmentation or opposition by other hormones

Question 18

Mechanism of testosterone action

Answer 18

• 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

Question 19

Why peptide hormones need cell membr receptors

Answer 19

• 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

Question 20

Action of finasteride

Answer 20

• 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

Question 21

Exogenous lipid pathway

Answer 21

Chylomicrons transport ingested fats to adipose/liver

Question 22

Endogenous TG pathway

Answer 22

From liver to peripheries

Question 23

Reverse cholesterol transport

Answer 23

HDL transports chol from peripheral tissues to liver to be excreted as bile

Question 24

LDL receptor pathway

Answer 24

• LDL binds LDL receptors on plasma membr
• receptor-bound LDL gets internalized into vesicles
• LDL receptors released and recycled
• vesicles fuse with lysosomes and chol released
• chol down regulates LDL receptor expression and chol sysnthesis

Question 25

Response to over accumulation of chol in cells

Answer 25

• transcription of LDL receptors inhibited
• HMGCoa Reductase is inhibited (chol sysnthesis inhibited)
• ACAT activated (converts to chol esterase)

Question 26

Action of statins

Answer 26

• inhibit HMGCoa reductase
• block chol synthesis
• increase LDL receptors so more cellular uptake of chol
• decrease plasma LDL

Question 27

Explain gout

Answer 27

• excessive levels of uric acid in plasma
• Uric acid is poorly sol at physiological pH
• precipitates out of sol as crystals and into synovial joints
• interferes with smooth articulation

Question 28

Action of allopurinol

Answer 28

• suicide inhibitor of xanthine oxidase
• resembles structure of xanthine oxidase and permanently binds and inactivates this enzyme
• prevents prod of Uric acid