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1 GI and liver > liver: lipoproteins, fatty acid oxidation, detoxification, bile > Flashcards

liver: lipoproteins, fatty acid oxidation, detoxification, bile Flashcards

1
Q

what is the structure of a lipoprotein?

A

outside - protein layer

inside - fat (protected)

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2
Q

what determines the density of a lipoprotein?

A

the protein to lipid ratio

ie. HIGH density = HIGH ratio (lots of protein, less fat)

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3
Q

HDL’s

- good or bad?

A

good

high protein:lipid

ie. not many lipids

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4
Q

HDL’s

- function

A

essentially empty inside as no fats

so removes excess cholesterol from blood and tissue

deliver to liver (excreted as bile)

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5
Q

HDLs

- where are they synthesised?

A

in liver

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6
Q

LDLs

- good or bad?

A

bad

low protein:lipid

ie. lots of fat inside (TCAs)

deposits can cause build up of cholesterol eg. in arterial walls

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7
Q

LDL’s

- function

A

deliver their cholesterol to different cells in body via endocytosis

cholesterol is used to synthesis cell membrane components and steroid hormones

bad if too much

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8
Q

VLDLs

- good or bad

A

very low protein:lipid

aka.chylomicrons

highest amount or TAGs

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9
Q

where are lipoproteins synthesised?

A

HDLs - liver
LDLs - plasma
VLDs - liver

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10
Q

VDLS

- function

A

carries TGs from glucose in liver to adipocytes

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11
Q

IDLs

- what are they?

A

intermediate

covert to LDLs

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12
Q

what is the purpose of fatty acid catabolism?

A

provides long-lasting energy for when body is in FASTED state

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13
Q

describe the levels of insulin and glucagon when body is in FASTED state?

A

high glucagon

low insulin

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14
Q

what is the main type of fatty acid beta oxidation?

A

mitochondrial

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15
Q

what is the functional group of a fatty acid?

A

C double bond O

carboxyl

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16
Q

what is the functional group of a glycerol molecule?

A

-OH

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17
Q

what is phase 1 of fatty acid catabolism?

A

free fatty acids transported from adipocyte to target cell

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18
Q

what is phase 2 of fatty acid catabolism?

A

fatty acid enters the mitochondria

- via the carinine mechanism

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19
Q

what are the 3 regulators of the carinine mechanism,?

A

CPT: carinine palmitosyl transferase

the carinine concentration

malonyl-coA : inhibits CPT

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20
Q

what is phase 3 of fatty acid catabolism?

A

beta oxidation

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21
Q

during beta oxidation of FAs, what enzyme links to the FA to activate it?

what is the product?

A

Coenzyme A

replaces -OH

makes an acetyl CoA subunit

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22
Q

why do beta oxidation reactions repeat?

A

each oxidation reaction shortens the R chain on the acetyl coA subunit by 2 C atoms

the shorter the chain, the easier it is to condense it into a ketone body, and then it can be fed into the TCA cycle and provide energy

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23
Q

what are xenobiotics?

A

foreign substances (eg. drugs, alcohol) that are not metabolised by body (because no nutritional value) and so need to be excreted

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24
Q

why is it difficult to excrete xenobiotics?

A

they are often lipophilic, non-polar, insoluble, non-ionised

not very suitable to be excreted in urine or bile

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25
Q

the liver, during detoxification, modifies xenobiotics to make them more suitable for excretion. how does it make them ‘more soluble’ ?

A

makes metabolites that are soluble and hydrophilic

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26
Q

what is phase 1 of detoxification of xenobiotics?

A

biotransformation reactions

  • reactions that dd a functional group to create a small increase in hydrophilicity
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27
Q

give 3 types of biotransformation reaction

A

oxidation

reduction

hydrolysis

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28
Q

which is the most common biotransformation reaction ?

what enzyme catalyses it?

A

oxidation: add -OH

uses the microsomal enzyme CYP 450

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29
Q

what are microsomal enzymes?

A

microsome = small particle consisting of a piece of endoplasmic reticulum to which ribosomes are attached

microsomal enzymes are found within these

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30
Q

what factors can induce/inhibit a biotransformation reaction ?

A

drugs, food, age, bacterial, alcohol

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31
Q

give 2 differences between microsomal and non-microsomal enzymes?

A

microsomal

  • specific (mainly used in phase I biotransformation reactions)
  • within Endoplasmic reticulum

non-micromsal

  • non specific but mainly II
  • within mitochondria/cytoplasm
32
Q

what are CYPs?

A

= cytochrome P450 enzymes

used for biotransformation reactions

generate a free radical

are microsomal

33
Q

give 2 factors that induce CYPs?

A

smoking and grapefruit

34
Q

what is phase 2 of detoxification of xenobiotics?

A

conjugation

-bind the xenobiotic to a very hydrophilic molecule (covalently)

35
Q

explain the most common conjugation reaction

A

glucuronidation

  • conjugates to glucuronic acid molecule
  • makes the xenobiotic much more hydrophilic
36
Q

what enzyme catalyses glucuronidation? is it microsomal or non-microsomal?

A

microsomal enzyme
- only microsomal for conjugation reactions (all the rest are NON)

glucuronosyltransferase (UGT)

37
Q

give an example of a non-microsomal enzyme?

A

non-microsomal are involved in all conjugation reactions except glucuronidation

eg. alcohol dehydrogenase

38
Q

alcohol detoxification:

- what does alcohol dehydrogenase convert alcohol to? (1)

A

acetaldehyde

39
Q

alcohol detoxification:
- what does acetaldehyde dehydrogenase convert acetaldehyde to? (2)

what is the product used for?

A

acetate

  • intermediate for krebs (why alcohol can be an energy source)
  • converted into CO2 and H2O
40
Q

what can happen during alcohol detoxification if too much alcohol is consumed to quickly?

A

the 2nd metabolism reaction is overwhelmed

build up of toxic acetaldehyde intermediate

liver damage

41
Q

what can go wrong during paracetamol detoxification ?

A
  • overwhelmed

- build up of harmful NAPQI intermediate

42
Q

what is bile made up of?

A

2/3 bile salts

1/3 phospholipids

+ bilirubin, electrolytes, xenobiotics etc.

43
Q

what are bile salts made of?

A

conjugated bile acids

w/ glycine or taurine

44
Q

what is bilirubin?

A

yellow pigment made from breakdown

45
Q

ARE BILE ACIDS HYDROPHOBIC OR hydrophilic?

A

both

amphipathic

46
Q

bile acid function

A

induces bile flow

cholesterol hoemostasis

protein absorbtio

digests dietary fats

removes xenobiotics

induces secretion of biliary lipids

prevents calcium gallstones and oxalate renal stones

47
Q

what is in the portal triad?

A

hepatic portal venuole

hepatic arteriole

common bile duct

48
Q

what is the first step of bile acid formation ?

A

cholesterol in hepatocytes

converted to 2 primary bile acids that are water soluble

49
Q

when do the primary bile acids become the secondary bile acids?

A

in the small intestine due to presence of bacteria

50
Q

what is enterohepatic circulation?

A

movement of bile acid from liver into small intestine and back to liver

51
Q

how do the bile salts get transported into the duodenum? (8)

A
  1. canaliculus
  2. ductules
  3. R&L hepatic ducts
  4. common hepatic duct
  5. common bile duct (also receives gall bladder contents via cystic duct)
  6. pancreatic duct feeds in
  7. ampulla of vater (through sphincter of oddi)
  8. duodenum
52
Q

what % of bile salts are reabsorbed from terminal ilium (enterohepatic circulation) ?

A

95%

53
Q

what is the transporter that allows bile salt reabsorption at terminal ileum?

what type of transport is it?

A

apical sodium bile acid transporter

by active transport

54
Q

through what vein do the bile salts travel back to liver in the enterohepatic circulation?

A

the portal vein

55
Q

what does FXR do in the enterohepatic circulation?

A

involved in negative feedback - slows circulation down

synthesis FGF-19 hormone which inhibits formation of primary bile acids

56
Q

where do bile acids go in fasted state?

no food being digested

A

stored in gallbladder

concentrated by 10x

57
Q

in FED state, what does CCK hormone do?

A

Cholecystokinin

  1. relaxes sphincter of oddi, allowing common bile duct and pancreatic duct to empty into duodenum
  2. stimules gall bladdder contraction, which squeezes bile into duodenum
58
Q

in what form is cholesterol secreted from body?

A

as bile

59
Q

how do statins affect cholesterol homeostasis?

A

statins inhibit HMG coA reductase

this stops cholesterol from forming

60
Q

what does ezetimibe do in cholesterol homeostasis?

A

stops transport of cholesterol into enterocyte membrane (into SI) causing it to be excreted

61
Q

what breaks fat down slightly into emulsion droplets?

how are these droplets prevented from reclumping?

A

motility

bile salts and phospholipids coat surface to stop it from reforming

forms a hydrophobic outside

62
Q

what doe lipase break a fat globule into?

A

1 monoglyeride (glycerol + 1 FA)

2 FAs

these are called micelles, and they are continuously broken down and reformed

63
Q

where do micelles transport to after breakdown/reformation process

A

diffuse into enterocytes in SI

here they reform TAGs

64
Q

what is glycogenolysis?

A

hydrolysis of glycogen to monomers of glucose-6-phosphate

within liver and skeletal muscles

65
Q

what is the functional unit of the liver?

A

hepatic lobule

66
Q

explain where the blood drains from the hepatic venuole and arteriole

A

portal triad - central vein of the lobular - joins with other central veins to form interlobular vein - joins with others to make hepatic vein - IVC

67
Q

what blood is in the hepatic sinusoid?

A
  • O2 rich from hetpric arteriole
  • nutrient rich from portal vein

mixed as it flows from sinusoids into centra vein

68
Q

what is the life span of a RBC?

A

120 days

69
Q

where are RBC broken down in the liver?

A

kuppfer cells (macrophages)

70
Q

what is haemoglobin broken down into during catabolism?

where does this happen?

A

phagocytosis in macrophage

haem and globin (globin is broken down into AAs, used )

71
Q

what is haem broken don into during catabolism (catalysed by haaemoxygenase)

A

biliverdin

Fe2+ & CO

72
Q

what is biliverdin converted into?

A

bilirubin (unconjugated)

73
Q

what enzyme allows bilirubin to become conjugated?

A

UGT

74
Q

where does conjugated bilirubin travel?

A

through bile duct and into duodenum

from here can go to fences, enterohepatic circulation or kidney as urobilin

75
Q

what colour is bilirubin?

A

yellow

76
Q

what causes jaundice?

A

yellow discolouration of skin caused by high serum bilirubin levels

77
Q

what are the 3 types of jaundice?

A

pre hepatic

hepatic

post hepatic/obstructive

1 GI and liver (6 decks)

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