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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?

24
Q

What happens in the first stage of liver damage?

A

Fatty liver

25
What happens in the second stage of liver damage?
Alcoholic hepatitis, groups of cells die -> inflammation
26
What happens in the third stage of liver damage?
Cirrhosis (fibrosis, scarring and cell death)
27
What happens when your liver is cirrhotic?
Liver cant function so | Ammonia accumulates -> neurotoxicity, coma and death
28
What % of alcoholics get cirrhosis?
25
29
What % of cirrhosis is due to alcohol?
75
30
What are the consequences of having high NADH levels as a result of high ethanol metabolism?
- 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
What does the increase in lactate lead to?
Hypoglycaemia and lactic acidosis
32
What molecules inhibit glucose metabolism and how?
Acetyl CoA, NADH and ATP Inhibiting PFK and pyruvate dehydrogenase
33
What are xenobiotics?
Compounds with no nutritional value
34
Give some examples of xenobiotics
``` Plant metabolites Synthetic compounds Food additives Agrochemicals Cosmetics Drugs ```
35
What organ plays a big role in xenobiotics metabolism?
Liver
36
What is the aim of xenobiotic metabolism?
Make them harmless and more readily disposed of
37
What are the three common phases in the metabolism of xenobiotics?
``` Phase 1 (oxidation) Phase 2 (conjugation) Phase 3 (elimination) ```
38
What happens in phase 1 of xenobiotic metabolism?
Oxidation mainly, but also hydroxylation and reduction
39
What does the modification do in phase 1 xenobiotic metabolism?
Increases solubility and introduces functional groups which enables participation in further reactions
40
What is phase 1 xenobiotic metabolism promoted by?
Cytochrome P450
41
Where is cytochrome P450 mainly found?
Liver and intestinal cells
42
How many enzymes are in the cytochrome P450 family?
50 enzymes
43
What do the cytochrome P450 enzyme family all have in common?
All haem proteins that relate to mitochondria enzymes
44
Where are the cytochrome P450 enzymes found within a cell?
Endoplasmic reticulum
45
What induces cytochrome P450 enzymes?
Their own substrates or related substrates
46
What groups are added in phase 2 xenobiotic metabolism?
Glutathione Glucaronic acid Sulfate
47
Why are the groups added in phase 2 xenobiotic metabolism?
Increase solubility and target for excretion
48
Why is the liver important in drug metabolism?
- xenobiotic metabolism is part of body’s natural defence | - metabolism of drugs plays a significant role in their effectiveness
49
What does metabolism of drugs do to their effectiveness?
Either increase or reduce depending on the drug
50
Can the body distinguish between harmful compounds and beneficial compounds?
No
51
What is aflatoxin B1 (Subscript 1) produced by?
Aspergillus flavus fungus
52
What happens when aflatoxin B1 undergoes metabolism?
Activated by P450 isenzymes -> epoxied formation and hepato-carcinogenesis
53
What do statins do?
Inhibit HMG-CoA
54
What are statins degraded by?
CVP3A4
55
What is CYP3A4 actively inhibited by?
Grapefruit juice
56
What happens after the compounds have been modified?
- 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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