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Gastrointestinal > Metabolic Functions of the Liver > Flashcards

Metabolic Functions of the Liver Flashcards

1
Q

How does the liver decrease Blood glucose levels?

A

By regulating flux into the pathways that remove free glucose, the liver contributes to lowering BGL

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2
Q

How do other organs contribute to lowering BGL?

A

Other organs (adipose tissue and muscle) also switch on their biosynthetic pathways to remove glucose from the blood

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3
Q

How does the liver maintain constant BGL?

A
  • Removal of glucose from blood post meal
  • Storing glucose as glycogen
  • Restoring BGL via gluconeogenesis + glycogenolysis
  • Regulating fluxes through glycolysis, pentose phosphate
    cycle + gluconeogenesis
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4
Q

Which sugars does the liver metabolise?

A

The liver is involved in metabolism of other sugars e.g. fructose and galactose as well as glucose

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5
Q

What role does the liver play in protein synthesis?

A

The liver is the major site for serum protein synthesis

e.g. albumin and blood clotting factors

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6
Q

What is the fate of excess amino acids in the body?

A

The liver degrades excess amino acids especially during gluconeogenesis

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7
Q

What are glucogenic amino acids degraded into?

A

glucogenic amino acids → sugars

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8
Q

What are ketogenic amino acids degraded into?

A

ketogenic amino acids → ketone bodies

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9
Q

What role does the liver play in the removal of toxic ammonia?

A

Major site for transamination + deamination of amino acids and detoxification of ammonia

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10
Q

What is the significance of liver interaction with muscle?

A

Important in regulating BGL available to tissues

Important in converting metabolites → proteins / sources of energy

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11
Q

How does the liver regulate fats and lipids in the body?

A

The liver also plays a central role in the synthesis, transport and metabolism of lipids and fats

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12
Q

How does cholesterol enter the livers cholesterol pool?

A
  • dietary
  • de novo via extra-hepatic tissue
  • endogenous (own production)
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13
Q

Where is the body’s cholesterol made from?

A

50% cholesterol made by liver
rest produced by intestine, adrenal cortex, and reproductive tissue
Made from acetyl coA (HMG CoA reductase)
Transported from liver as VLDL

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14
Q

How is cholesterol excreted from the body?

A

Body can’t degrade cholesterol

Disposed by biliary system in intestines as either cholesterol following conversion to bile acids/salts

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15
Q

Why is ethanol metabolism significant?

A

Need to metabolise ethanol as its present as a consequence of either diet or lifestyle

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16
Q

What are the 2 routes of ethanol metabolism?

A
  1. Oxidation (via alcohol dehydrogenase)

2. Microsomal Oxidation (via cytochrome p450)

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17
Q

Outline the metabolism of ethanol

A

ethanol → acetaldehyde →acetate

using enzymes alochol and actealdehyde dehydrogenases

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18
Q

What is the consequence of methanol metabolism?

A

Methanol→formaldehyde - v. toxic

associated with paralysis, loss of consciousness and blindness

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19
Q

Explain how certain ethnicities are intolerant to ethanol

A

40% of asians are intolerant to ethanol showing symptoms of:

- tachycardia, facial flush, vasodilation and nausea

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20
Q

What are the products of ethanol metabolism?

A

Oxidation of alcohol takes precedent over other nutrients and isn’t regulated by negative feedback so large quantities of NADH, ATP and acetyl CoA are formed
- can cause inhibition of certain metabolic pathways

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21
Q

Which pathways are inhibited due to ethanol metabolism?

A

Acetyl CoA, NADH + ATP
- inhibit glucose metabolism by inhibiting PFK + pyruvate
dehydrogenase

NADH
- inhibits tca cycle + acetyl CoA increases further

Acetyl CoA
- Causes ketone body formation + FA synthesis
stimulation
- FA esterified to TG for VLDL export

22
Q

What does MESO stand for?

A

Microsomal Ethanol Oxidising System

23
Q

What is MESO?

A

2nd route of metabolism
involves oxidation of ethanol by cytochrome P450 family
uses NADPH required for GSH synthesis

24
Q

Outline features of acetaldehyde

A
  • highly reactive (accumulates w/ excessive alcohol)
  • can inhibit enzyme functions
  • liver leads to reduce serum protein and VLDL secretion
  • Can enhance free radical production →leads to tissue
    damage e.g. inflammation + necrosis
25
Q

What are the 3 stages of liver damage?

A

Stage 1: fatty liver
Stage 2: Alcoholic hepatitis, necrosis = inflammation
Stage 3: Cirrhosis, fibrosis, scarring and cell death

26
Q

What is the consequence of cirrhosis?

A

As cirrhotic liver can’t function properly, ammonia accumulate resulting in neurotoxicity, coma and death

27
Q

What are xenobiotics?

A

Compounds with no nutritional value

28
Q

Give examples of xenobiotics

A 
Plant metabolites
Synthetic compounds
Food additives
Agro-chemicals
Cosmetics
By products of cooking 
drugs
29
Q

What is the advantage of water soluble compounds in excretion?

A

Water soluble compounds are easily excreted in urine

Lipophilic compounds are harder to excrete

30
Q

What are the three phases of xenobiotic metabolism?

A
  1. Oxidation
  2. Conjugation
  3. Elimination
31
Q

Describe the effects of Phase 1: oxidation

A

Increases solubility
Introduces functional groups - allows further reactions
Promoted by Cytochrome p450

32
Q

Where are cytochrome p450 enzymes found?

A

Found mainly in liver and intestinal Cells; ER

33
Q

How are cytochrome p450 enzymes induced?

A

own substrates or related substrates activate cytochrome p450 enzymes - clinically significant

34
Q

Explain how xenobiotic conjugation occurs

A

Xenobiotics are modified by addition of groups such as:

  • Glutathionine
  • Glucoronic acid
  • Sulphate

compounds are often sequentially modified

35
Q

What is the benefit of xenobiotic conjugation?

A

Modification with these groups increases solubility and targets them for excretion

36
Q

What is the significance of liver drug metabolism?

A

Xenobiotic metabolism is part of the body’s natural defences but the body doesn’t distinguish between harmful and beneficial compounds e.g. therapeutic drugs

37
Q

How does liver metabolism of drugs affect their effectiveness?

A

orally taken - passes through liver first

modifications made by the liver can significantly reduce effectiveness but this can also be advantageous

38
Q

What is the function of statins?

A

inhibit HMG CoA Reductase

degraded by CYP3A4 (inhibited by grapefruit juice)

39
Q

How is aflatoxin B1 produced?

A

By fungus aspergillus Flavus

Activated by P450 enzymes leading to epoxide formation and hepatocarcinogenesis

40
Q

Explain the metabolism of paracetamol in the liver

A

Hepatic metabolism of paracetamol→reactive intermediate NAPQI formed
Under normal physiological conditions NAPQI is cleared via conjugation with GSH (glutathionine)

41
Q

What is the effect of NAPQI if not cleared?

A

NAPQI forms NAPQI-protein adducts resulting in:

  • oxidative stress
  • mitochondrial dysfunction
  • necrotic cell death
42
Q

Why may NAPQI not be cleared?

A

Due to low GSH levels/ excessive alcohol consumption
→Activation of MESO (microsomal ethanol-oxidising
system) using NADPH which is required for GSH
synthesis

43
Q

How does ethanol metabolism affect NAPQI clearance?

A

Ethanol metabolism →NADPH reduction = less GSH to clear NAPQI →NAPQI builds up causing liver damage

44
Q

What is the fate of modified compounds?

A

Small water soluble compounds excreted via kidneys

Some actively transported in to bile → intestines

45
Q

Explain what happens to compounds that are modified?

A

Fate of these is 3 fold

  • digestion
  • absorption
  • reabsorption via enterohepatic circulation
46
Q

How long does it take for 50% of a substance to be excreted fully?

A

t 1/2 is the time required for 50% of a substance to be lost

47
Q

Explain the role the liver plays in carbohydrate metabolism

A

Regulates carbohydrate metabolism

- to maintain BGL

48
Q

Explain the role the liver plays in fat metabolism

A

Regulates fat metabolism

  • lipid synthesis
  • beta oxidation
49
Q

Explain how the liver regulates protein metabolism

A

plasma protein synthesis

detoxification of ammonia → urea formation

50
Q

What roles does the liver play in regulating cholesterol?

A

Regulates cholesterol synthesis and excretion

Gastrointestinal (18 decks)

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