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Alim 1 > metabolic functions of the liver > Flashcards

metabolic functions of the liver Flashcards

1
Q

how does the liver lower blood glucose

A

by regulating flux into the pathways that remove free glucose

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2
Q

what compounds does the liver receive from muscle

A

lactate and alanine

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3
Q

how are alanine and lactate processed in the liver

A

both converted into pyruvate

glu-6-p > glucose which is transported to the muscle

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4
Q

where are albumin and serum proteins mostly synthesised

A

the liver

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5
Q

when especially does the liver degrade amino acids

A

gluconeogenesis

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6
Q

how are AAs processed in the liver

A

deamination
transamination
detoxification

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7
Q

sources of liver choleserol

A

de novo synthesis in the liver
dietary cholesterol - chylomicron remnants
cholesterol from extrahepatic tissue

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8
Q

how does cholesterol leave the liver

A

free in bile
converted to bile acid
secretion of VLDL

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9
Q

how is cholesterol synthesised in the liver

A

from acetyl CoA, using HMG-CoA reductase

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10
Q

how is cholesterol transported from the liver

A

VLDL

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11
Q

how is cholesterol secreted

A

biliary system as cholesterol or following conversion to bile acids

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12
Q

what are the two routes of ethanol digestion

A

oxidation through alcohol dehydrogenase

microsomal ethanol oxidising system (MEOS_ on using cytochrome P450

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13
Q

metabolism of alcohol in the cytosol

A

ethanol > acetaldehyde via NAD+ > NADH, H+

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14
Q

alcohol metabolism in the mitochondria

A

acetaldehyde > acetate via NAD+ & H2O > NADH & 2H+

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15
Q

what enzyme converts ethanol to acetaldehyde

A

alcohol dehydrogenasea

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16
Q

what enzyme converts acetaldehyde to acetate

A

aldehyde dehydrogenase

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17
Q

what does methanol get metabolised to

A

formaldehyde - toxic >paralysis, loss of consciousness, blindness

18
Q

why are large quantities of acetyl-CoA, NADH, and ATP formed from alcohol metabolism

A

oxidation of alcohol takes precedence over other nutrients

alcochol metabolism isn’t regulated by negative feedback

19
Q

how does alcohol metabolism inhibit the TCA cycle

A

high levels of ATP and NADH and NAD+ depletion inhibit TCA cycle

20
Q

how does ethanol oxidation lead to oxidative stress

A

microsomal oxidation by cytochrome P450 enzymes leads to oxidative stress

21
Q

how does excess alcohol metabolism cause fatty liver?

A

FA synthesis stimulated, as well as esterification to TGs to get exported as VLDL

22
Q

effect of acetaldehyde on the liver

A

reacts with/inhibits proteins - leads to reduction of secretion of serum protein and VLDL by the liver

23
Q

how can acetaldehyde cause inflammation and necrosis

A

by enhancing free radical production

24
Q

the 3 stages of liver damage

A

1 - fatty liver
2 - alcoholic hepatitis
3 - cirrhosis: fibrosis, scarring, cell death

25
Q

how can a cirrhotic liver be lethal

A

ammonia accumulates due to poor function, resulting in neurotoxicity, coma, and death

26
Q

what pathways are inhibited by ethanol metabolism

A

gluconeogenesis
lactate > pyruvate
FA > acetyl CoA
TCA

27
Q

what are xenobiotics

A

compounds with no nutritional value

28
Q

phases of xenobiotic metabolism

A
  1. oxidation
  2. conjugation
  3. elimination
29
Q

what is the point of xenobiotic oxidation

A

increases solubility

introduces functional groups for further reactions

30
Q

what promotes oxidation of xenobiotics

A

cytochrome P450 enzymes

31
Q

where are cytochrome P450 enzymes found

A

ER of liver and intestinal cells

32
Q

what type of proteins are CP450 enzymes

A

haem, related to the mitochondrial enzymes

33
Q

example of CP450 action

A

hydroxylation of ibuprofen

34
Q

what can induce CP450 enzymes

A

their own substrates AND related substrates

35
Q

what happens in conjugation of xenobiotics

A 
modified by addition of groups like
glutathione
gluguronic acid
sulphate
- increases solubility and makes them a target for secretion
36
Q

what is the main action of statins

A

inhibit HMG-CoA reductase

37
Q

what degrades statins

A

CYP3A4

38
Q

what can inhibit CYP3A4

A

grapefruit juice

39
Q

what happens if you drink grapefruit juice while on statins

A

statin levels can rise by 15 fold because they’re not degraded

40
Q

what is aflatoxin b1 activated by

A

P450 isoenzymes

41
Q

what is the result of aflatoxin b1 activation

A

epoxide formation and hepatocarcinogenesis

42
Q

what happens to modified compounds

A

now soluble - can be removed by kidney
active transport into bile > intestines
can be reabsorbed

Alim 1 (11 decks)

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