Liver function

Question 1

why is cholesterol important

Answer 1

synthesis of cell membranes and contributes to fluidity
lipid rafts- patches of fluidity
precursor for synthesis of several molecules eg vit D

Question 2

cholesterol synthesis

Answer 2

80% production in the liver
from Acetyl CoA
Multi step pathway

Question 3

cholesterol synthesis step 2/3

Answer 3

squalene synthesised from isopentenyl pyrophosphate
cyclization of squalene to form lanosterol
lanosterol goes through several steps to form cholesterol

Question 4

statins

Answer 4

inhibit HMG CoA-reductase in cholesterol synthesis pathway

Question 5

how is cholesterol transported in the body and why

Answer 5

lipophilic so does not dissolve well in water.
Packaged with phospholipids and apolipoproteins to form a series of different lipoproteins (have a lipid core and hydrophlic outer surface with phospholipids, free cholesterol and apolipoproteins.
include LDLs and HDLs

Question 6

How to treat atherosclerosis

Answer 6

Inhibit cholesterol synthesis, because high LDL levels associated with atherosclerosis

Question 7

HDL vs LDL

Answer 7

Ldl risk factor of CVD and athersclerosis, HDL protective

Question 8

Bile salt production recap

Answer 8

Primary bile salts formed in the liver, go into GI tract, where modified by gut bacteria to form secondary bile salts
dehydroxylation

Question 9

bile contains

Answer 9

bile salts
lecithin
HCO3-
cholesterol
bile pigments
trace metals

Question 10

Bile production

Answer 10

Hepatocytes secrete hepatic bile into canaliculi

Question 11

hepatic bile

Answer 11

bile salts, bile pigments, cholesterol and lecithin

Question 12

what do epithelial cells that line the bile ducts secrete

Answer 12

a bicarbonate rich fluid that increases the volume of the bile

Question 13

what are precursors of bile salts

Answer 13

bile acids synthesized from cholesterol

Question 14

Primary bile acids

Answer 14

cholic acid and chenodeoxycholic acid

synthesised in the hepatocytes

Question 15

secondary bile acids

Answer 15

deoxycholic and lithocholic- are formed inthe intestine by the dehydroxylating action of bacteria flora

Question 16

conjugation

Answer 16

in the liver, primary or secondary bile acids are conjugated to amino acids to generate water soluble bile salts

Question 17

bile salts have

Answer 17

hydrophobic and hydrophilic regions that aggregate to form micelles at a critical concentration
Important for the emulsification of fats

Question 18

where are the majority of bile salts reabsorbed

Answer 18

by a sodium dependent pathway in the ileum (last segment of the small intestine)

Question 19

how do bile salts get recycled back to the liver from the intestine

Answer 19

portal vein

Question 20

how does uptake of bile salts from portal blood into hepatocytes occur

Answer 20

active transport

Question 21

enterohepatic circulation

Answer 21

recycling from the GI tract to the liver

Question 22

sphincter of oddi

Answer 22

ring of smooth muscle where common bile enters small intestine

Question 23

Cholecystokinin (CCK)

Answer 23

peptide hormone
produced by small intestine
stimulus for release- AAs, fatty acids in the intestine

Question 24

What does increased CCK lead to

Answer 24

gallbadder contraction, increased bile flow into common bile duct
relax sphincter of oddi, incr bile flow into duodenum

Question 25

what happens when the sphincter of oddi is closed

Answer 25

bile diverted to gall bladder

Question 26

what does the gall bladder do with bile stored for digestion

Answer 26

concentrates it by removal of salts and water

Question 27

bile pigments

Answer 27

breakdown product of heme portion of haemoglobin from erythrocytes broken down in the liver and spleen major pigment is bilirubin found in bile and secreted into duodenum pigments responsible for characteristic bile colour

Question 28

what else does the liver secrete

Answer 28

plasma proteins

Question 29

albumin

Answer 29

plasma protein, transport lipids and steroid hormones

Question 30

Globulins

Answer 30

approx 40% total plasma proteins | a-globulins and B-globulins also transport lipids and steroid hormones

Question 31

clotting factors

Answer 31

most produced by the liver

Question 32

IGF- insulin like growth factors

Answer 32

Important mediator of growth hormone action Liver synthesises IGF 1 and 2 in response to growth hormone structurally similar to pro-insulin

Question 33

IGF-1

Answer 33

levels low in infancy, peak in puberty during growth and declines in adult

Question 34

IGF 2

Answer 34

more important in fetal and neonatal growth

Question 35

Phase 1 reactions drug metabolism

Answer 35

Cytochrome p450 enzymes important Population variation in these is important in terms of therapeutics Naturally occurring dietary substances can inhibit or induce p450 enzymes with impact on drug metabolism

Question 36

clopidogrel

Answer 36

anti-thrombotic agent that inhibits platelet activation | pro drug that requires oxidation

Question 37

what is a pro drug

Answer 37

a biologically inactive compound which can be metabolized in the body to produce a drug.

Question 38

metabolism of clopidogrel

Answer 38

2 step, using hepatic P450 enzymes to generate the active thiol metabolite that reacts with platelets Binds selectively and irreversibly to P2Y12 receptor on platelet membranes

Question 39

What happens to majority of clopidogrel

Answer 39

inactivated by blood esterases so only 15 % metabolised by hepatic P450 enzymes

Question 40

What are mutations in P450 enzymes associated with

Answer 40

reduced response to clopidogrel treatment

Question 41

Phase 2 reactions

Answer 41

conjugation step that leads to pharmacologically inactive or less soluble lipid product that is eliminated in urine or bile

Question 42

groups often associated with conjugation

Answer 42

glucuronyl, sulphate, methyl, acetyl etc

Question 43

what is paracetamol

Answer 43

non-narcotic analgesic-antipyretic agent

Question 44

paracetamol peak plasma conc

Answer 44

30-60 mins

Question 45

paracetamol inactivated in liver by

Answer 45

conjugation to glucuronide or sulphate

Question 46

Toxic dose causes

Answer 46

hepatotoxicity and renal toxicity

Question 47

what happens with paracetamol toxic dose

Answer 47

normal conjugation pathways saturated and drug metabolised by mixed function oxidases to form N-acetyl-p-benzoquinone imine (NAPBQI)- toxic to cells

Question 48

kupffer cells function

Answer 48

phagocytize pathogens from entering blood circulation | first line of defence against particulates and immunoreactive material from GI tract via portal circulation

Question 49

cholesterol synthesis 1st step

Answer 49

Acetyl CoA is joined to acetoacyl CoA to form HMG CoA. This product is converted to melvalonate by HMG-CoA reductase. Mevalonate is phosphorylated by three kinases sequentially utilizing three ATPs and is then decarboxylated to form isopentenyl diphosphate.

Question 50

cholic forms

Answer 50

deoxycholic

Question 51

chenodeoxycholic forms

Answer 51

lithocholic

Question 52

phase 1 reaction processes

Answer 52

``` Oxidation Hydroxylation Dealkylation Deamination hydrolysis ``` involve the creation of a functional group or the modification of an existing one by oxidation, reduction, or hydrolysis.