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Physiology 1 > Metabolic Functions Of The Liver > Flashcards

Metabolic Functions Of The Liver Flashcards

1
Q

Why does the liver regulate carbohydrate metabolism?

A

To maintain blood glucose

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2
Q

Why does the liver regulate fat metabolism?

A

Synthesis and beta oxidation

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3
Q

Why does the liver regulate protein metabolism?

A

Plasma protein synthesis

Detoxification of ammonia (urea formation)

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4
Q

What specialised molecule does the liver synthesise?

A

Bile acids

Haemin

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5
Q

What else does the GI tract supply to the liver?

A

Major dietary nutrients (proteins and carbs- not lipids)

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6
Q

Where does the livers blood empty into and why?

A

Inferior vena cava

Ensures fast circulation of products

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7
Q

Where does the bile duct empty into?

A

The gut

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8
Q

What are the routes of ethanol metabolism (and their % prevalence)?

A

Oxidation through activity of alcohol dehydrogenase (90%)

Miscrosomal oxidation using cytochrome P450 (10-20%)

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9
Q

How much alcohol does the body metabolise through oxidation per hour?

A

10g

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10
Q

What does methanol oxidise to?

A

Formaldehyde

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11
Q

Why is the oxidation of methanol bad?

A

Formaldehyde is super toxic and can lead to blindness, paralysis and loss of consciousness

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12
Q

What isoform(s) of ALDH do Caucasians have?

A

ALDH-1 and 2

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13
Q

Where is ALDH2 found?

A

Mitochondria

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14
Q

What percentage of certain ethnic groups only express which enzyme?

A

40%

ALDH1

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15
Q

What are the symptoms of ethanol intolerance?

A

Vasodilation, facial flush, tachycardia and nausea

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16
Q

What happens in the microsomal ethanol-oxidising system?

A

Ethanol is oxidised by members of cytochrome P450 family

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17
Q

What does the microsomal ethanol-oxidising system generate?

A

Acetaldehyde

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18
Q

What does the microsomal ethanol-oxidising system consume?

A

NADPH

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19
Q

What is NADPH needed for?

A

Synthesis of gluthathione (antioxidant) -> increased oxidative stress

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20
Q

When does acetaldehyde accumulate?

A

Excessive ethanol intake

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21
Q

What are the effects of acetaldehyde?

A
  • Inhibited enzyme function
  • Decreased secretion of serum protein and VLDL in the liver
  • enhanced free radical production
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22
Q

What do free radicals do in the body?

A

Lead to tissue damage (inflammation and necrosis)

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23
Q

How many stages of liver damage are there?

A

3

24
Q

What happens in the first stage of liver damage?

A

Fatty liver

25
Q

What happens in the second stage of liver damage?

A

Alcoholic hepatitis, groups of cells die -> inflammation

26
Q

What happens in the third stage of liver damage?

A

Cirrhosis (fibrosis, scarring and cell death)

27
Q

What happens when your liver is cirrhotic?

A

Liver cant function so

Ammonia accumulates -> neurotoxicity, coma and death

28
Q

What % of alcoholics get cirrhosis?

A

25

29
Q

What % of cirrhosis is due to alcohol?

A

75

30
Q

What are the consequences of having high NADH levels as a result of high ethanol metabolism?

A
  • inhibits glucogenesis and stimulates the conversion of pyruvate -> lactate
  • inhibits fatty acid oxidation
  • Inhibits TCA cycle and acetyl coA increases inhibition further
  • stimulates fatty acid synthesis
  • stimulates formation of TGs
31
Q

What does the increase in lactate lead to?

A

Hypoglycaemia and lactic acidosis

32
Q

What molecules inhibit glucose metabolism and how?

A

Acetyl CoA, NADH and ATP

Inhibiting PFK and pyruvate dehydrogenase

33
Q

What are xenobiotics?

A

Compounds with no nutritional value

34
Q

Give some examples of xenobiotics

A 
Plant metabolites
Synthetic compounds
Food additives
Agrochemicals
Cosmetics
Drugs
35
Q

What organ plays a big role in xenobiotics metabolism?

A

Liver

36
Q

What is the aim of xenobiotic metabolism?

A

Make them harmless and more readily disposed of

37
Q

What are the three common phases in the metabolism of xenobiotics?

A 
Phase 1 (oxidation) 
Phase 2 (conjugation)
Phase 3 (elimination)
38
Q

What happens in phase 1 of xenobiotic metabolism?

A

Oxidation mainly, but also hydroxylation and reduction

39
Q

What does the modification do in phase 1 xenobiotic metabolism?

A

Increases solubility and introduces functional groups which enables participation in further reactions

40
Q

What is phase 1 xenobiotic metabolism promoted by?

A

Cytochrome P450

41
Q

Where is cytochrome P450 mainly found?

A

Liver and intestinal cells

42
Q

How many enzymes are in the cytochrome P450 family?

A

50 enzymes

43
Q

What do the cytochrome P450 enzyme family all have in common?

A

All haem proteins that relate to mitochondria enzymes

44
Q

Where are the cytochrome P450 enzymes found within a cell?

A

Endoplasmic reticulum

45
Q

What induces cytochrome P450 enzymes?

A

Their own substrates or related substrates

46
Q

What groups are added in phase 2 xenobiotic metabolism?

A

Glutathione
Glucaronic acid
Sulfate

47
Q

Why are the groups added in phase 2 xenobiotic metabolism?

A

Increase solubility and target for excretion

48
Q

Why is the liver important in drug metabolism?

A
  • xenobiotic metabolism is part of body’s natural defence

- metabolism of drugs plays a significant role in their effectiveness

49
Q

What does metabolism of drugs do to their effectiveness?

A

Either increase or reduce depending on the drug

50
Q

Can the body distinguish between harmful compounds and beneficial compounds?

A

No

51
Q

What is aflatoxin B1 (Subscript 1) produced by?

A

Aspergillus flavus fungus

52
Q

What happens when aflatoxin B1 undergoes metabolism?

A

Activated by P450 isenzymes -> epoxied formation and hepato-carcinogenesis

53
Q

What do statins do?

A

Inhibit HMG-CoA

54
Q

What are statins degraded by?

A

CVP3A4

55
Q

What is CYP3A4 actively inhibited by?

A

Grapefruit juice

56
Q

What happens after the compounds have been modified?

A
  • Small, water soluble molecules (<60000 kDa) can be removed by the kidney
  • actively transported into bile and then into intestines

Physiology 1 (65 decks)

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