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SGUL - Physiology 1 > Metabolic Functions of the Liver > Flashcards

Metabolic Functions of the Liver Flashcards

1
Q

What relevance is the positioning/functioning of the liver in the body? PART 1

A
  • First major organ in line from the gut so handles large amounts of newly absorbed nutrients.
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2
Q

What relevance is the positioning/functioning of the liver in the body? PART 2

A
  • Positioned between the gut and the heart - ‘protects’ major vessels from direct contact with dietary nutrients
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3
Q

What relevance is the positioning/functioning of the liver in the body? PART 3

A

Empties directly into major vessel entering the heart - ensure rapid circulation of products.

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4
Q

What relevance is the positioning/functioning of the liver in the body? PART 4

A
  • Bile ducts empty directly into the gut - rapidly influence the digestive process.
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5
Q

How is the liver important in maintaining constant blood glucose levels?

A
  • removal of glucose from the blood after a meal
  • storing glucose in the form of glycogen
  • restoring blood glucose levels through glycogenolysis and gluconeogenesis
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6
Q

What is the importance of the liver for protein and amino acid metabolism? PART 1

A
  • Site for serum protein synthesis, such as albumin and blood clotting factors.
  • Degrades excess amino acids, particularly during gluconeogenesis
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7
Q

What is the importance of the liver for protein and amino acid metabolism? PART 2

A

Major site for transamination and deamination of amino acids, and detoxification of ammonia.

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8
Q

How does the liver degrade excess amino acids during gluconeogenesis?

A
  • Converts glucogenic amino acids to sugars
  • Converts ketogenic amino acids to ketone bodies
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9
Q

Describe the synthesis of cholesterol in the body.

A
  • 50% of cholesterol made in the body is made by the liver
  • Remainder synthesised by the intestine and adrenal cortex
  • Made from Acetyl CoA, and the key enzyme is HMG-CoA reductase
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10
Q

In what form is cholesterol transported?

A

As VLDL

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11
Q

Describe the excretion of cholesterol in the body.

A
  • Body cannot directly degrade cholesterol
  • Disposed of by the biliary system, either as cholesterol or by following the conversion to bile acids/salts
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12
Q

What are the two routes to the metabolism of alcohol?

A
  • oxidation through the activity of alcohol dehydrogenase (90%)
  • microsomal oxidation using cytochrome P450 (10-20%)
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13
Q

Describe the first step of the metabolism of alcohol (ie. ethanol to acetate).

A
  • In the cytoplasm, ethanol is converted to acetaldehyde by alcohol dehydrogenase
  • In the mitochondria, acetaldehyde is converted to acetate by aldehyde dehydrogenase
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14
Q

What is the rate-limiting enzyme within the conversion of ethanol to acetate?

A

Alcohol dehydrogenase

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15
Q

What can methanol be metabolised to form?

A

Formaldehyde

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16
Q

What are the effects of formaldehyde?

A
  • Paralysis
  • Loss of consciousness
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17
Q

Some people are more tolerant to alcohol than others. Suggest why.

A

Genetic variations in alcohol dehydrogenase which influence its rate, efficiency and structure

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18
Q

Describe the situation in which aldehyde dehydrogenase is rate limiting. PART 1

A
  • Single amino acid substitutions (e.g glutamine to lysine)
  • Produce dominant negative mutations
  • In heterozygotes, the normal enzyme will function as if mutated
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19
Q

Describe the situation in which aldehyde dehydrogenase is rate limiting. PART 2

A
  • Alcoholic treatment using aldehyde dehydrogenase inhibitor
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20
Q

What happens when NADH is used to treat alcoholics?

A
  • Poor inhibitor of both dehydrogenases
  • Will not affect either enzyme and will accumulate in cytosol
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21
Q

List some pathways inhibited by the metabolism of ethanol. PART 1

A
  • Acetyl-CoA, NADH and ATP inhibit glucose metabolism by inhibiting PFK and pyruvate dehydrogenase.
22
Q

List some pathways inhibited by the metabolism of ethanol. PART 2

A
  • NADH inhibits the TCA cycle, causing accumulation of acetyl-CoA
23
Q

How does ethanol metabolism trigger fatty acid synthesis and transport?

A
  • Acetyl-CoA triggers ketone body formation and stimulates fatty acid synthesis in cytosol.
  • Fatty acids are esterified to triglycerides for export as VLDL.
24
Q

What is the microsomal ethanol-oxidising system (MESO) and what does it need?

A
  • Oxidation by the members of the cytochrome P450 family of enzymes.
  • Uses NADPH which is required for the synthesis of the antioxidant glutathione.
25
Q

Describe acetaldehyde.

A

Highly reactive substance that accumulates with excessive ethanol intake.

26
Q

What is the effect of acetaldehyde on the liver?

A
  • Inhibit enzymes and their functions.
  • Reduction in the secretion of serum protein and VLDL.
27
Q

What process can acetaldehyde enhance?

A

Free-radical production

28
Q

What is the effect of free-radical production?

A

Inflammation and necrosis

29
Q

What is the first step of liver damage induced by alcohol abuse?

A

Fatty liver

30
Q

What is the second step of liver damage induced by alcohol abuse?

A
  • Alcoholic hepatitis
  • Cell death resulting in inflammation
31
Q

What is the third step of liver damage induced by alcohol abuse?

A

Cirrhosis - induces fibrosis, scarring and cell death

32
Q

What are the effects of cirrhotic liver?

A
  • Accumulation of ammonia
  • Neurotoxicity, coma and death follow
33
Q

What are xenobiotics?

A

Compounds with no nutritional value

34
Q

Give examples of xenobiotics.

A

plant metabolites
synthetic compounds
cosmetics
drugs

35
Q

What does the liver have to do with xenobiotic metabolism?

A
  • Make xenobiotics harmless and more readily disposed of by the kidney in the urine or the gut in the faeces.
36
Q

What are the three stages of the metabolism of xenobiotics?

A

PHASE 1: Oxidation
PHASE 2: Conjugation
PHASE 3: Elimination

37
Q

Describe the first stage (oxidation) of xenobiotic metabolism.

A
  • Introduces functional groups, which enables participation in further reactions and increases solubility.
  • Promoted by a family of enzymes called cytochrome P450.
38
Q

Describe cytochrome P450.

A
  • Found mainly in ER of liver and intestine cells
  • Haem proteins - also related to mitochondrial enzymes.
  • Inducible by both their substrates (5-10 fold), but also by related substrates (2-4 fold).
39
Q

Describe the second stage (conjugation) of xenobiotic metabolism.

A

Xenobiotics are sequentially modified by the addition of groups such as:
- glutathione
- glucuronic acid
- sulphate

40
Q

Outline the purpose of conjugation.

A

Increases their solubility and targets them for excretion.

41
Q

Describe aflatoxin B1.

A
  • Produced by the fungus Aspergillus flavus.
  • Activated by P450 isoenzymes, which leads to epoxide formation and hepatocarcinogenesis.
42
Q

What happens to the modified compounds?

A
  • Can be removed by the kidney.
  • Actively transported in the bile and then into the intestines.
43
Q

What are the three physiological processes that can happen to modified compounds?

A

digestion
excretion
reabsorption (via the enterohepatic circulation)

44
Q

Describe the glucose alanine cycle. PART 1

A

→In the muscle, branched amino acids are taken and broken down.
→Carbon skeleton is used for energy production.
→NH4 can be used to convert pyruvate to Alanine. Alanine is then exported into the blood and travels to the liver.

45
Q

Describe the glucose alanine cycle. PART 2

A

→ Alanine is then converted to glutamate via transamination (reacting with α-ketoglutarate) also producing pyruvate.
→The pyruvate can enter the gluconeogenic pathway to form glucose, and the glucose can be transported in the blood back to the muscle where it can be used for energy.

46
Q

Describe the glucose alanine cycle. PART 3

A

→The glutamate will then be used along with the CO2 generated to produce urea in the liver.

47
Q

What are the symptoms for ethanol intolerance?

A

→ Vasodilation
→ tachycardia
→ Nausea

48
Q

What is the consequence of alcohol metabolism not being regulated by negative feedback?

A

→ Large quantities of Acetyl CoA, NADH and ATP are formed

49
Q

RECAP TO FPP: Why is drug metabolism important and when can it be harmful?

A

→ Body cannot distinguish between harmful and beneficial compounds such as therapeutic drugs
→A drug taken orally will pass through the liver first
→ Modifications made by the liver can significantly reduce the effectiveness of a drug
→ Advantageous because the liver can activate the drug

50
Q

What do statins inhibit and what are they degraded by?

A

→ HMG- CoA reductase
→ Degraded by CYP3A4

SGUL - Physiology 1 (68 decks)

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