Metabolic functions of the liver

Question 1

What does the liver protect?

Answer 1

→ Major vessels from direct contact with dietary nutrients

Question 2

How does the liver contribute to the removal of glucose?

Answer 2

→ regulating the flux into pathways that remove free glucose

Question 3

How does the liver store glucose?

Answer 3

→ As glycogen

Question 4

How does the liver restore blood glucose levels?

Answer 4

→ Glycogenolysis

→ Gluconeogenesis

Question 5

What is the liver a major site of synthesis for?

Answer 5

→ Serum proteins such as albumin and blood clotting factors

Question 6

What does the liver do to excess amino acids during gluconeogenesis?

Answer 6

→ Degrades them

Question 7

What do glucogenic amino acids become?

Answer 7

→ Sugars

Question 8

What do ketogenic amino acids become?

Answer 8

→ Ketone bodies

Question 9

What does the liver do to amino acids?

Answer 9

→ Transaminate and deaminates them

Question 10

What happens to ammonia in the liver?

Answer 10

→ Gets detoxified

Question 11

Describe the glucose alanine cycle

Answer 11

→In the muscle, branched amino acids are taken and broken down.

→The carbon skeleton is used for energy production.

→ the NH4 can be used to convert to pyruvate to Alanine. Alanine is then exported into the blood and travels to the liver.

→ alanine is then converted to glutamate via transamination (reacting with α-ketoglutarate) also producing a 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.

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

Question 12

Where does synthesis of fatty acids take place?

Answer 12

→ In the cytosol of hepatocytes

Question 13

Where is the cholesterol in the body made?

Answer 13

→ 50% made by the liver

→ rest is made in the intestines, adrenal cortex and reproductive tissue

Question 14

What is cholesterol made from and what enzyme is used?

Answer 14

→ HMG- CoA reductase

→ Acetyle CoA is used

Question 15

How is cholesterol transported from the liver as?

Answer 15

→ VLDL

Question 16

How is cholesterol disposed of and why?

Answer 16

→ The body cannot degrade cholesterol

→ Disposed of by the biliary system as cholesterol or converted to bile acids or salts

Question 17

What are the two routes of metabolism of ethanol?

Answer 17

→ Oxidation through alcohol dehydrogenase - 90%

→ Microsomal oxidation using cytochrome P450 - 10-20%

Question 18

How much alcohol does the body metabolize per hour?

Answer 18

→ 10g

Question 19

What is methanol metabolized to and why is this bad?

Answer 19

→ Formaldehyde

→ Toxic and associated with paralysis, loss of consciousness, blindness

Question 20

What is the Km of ALDH2 ?

Answer 20

→ low

Question 21

What are the symptoms for ethanol intolerance?

Answer 21

→ Vasodilation
→ Facial flush
→ tachycardia
→ Nausea

Question 22

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

Answer 22

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

Question 23

What are the pathways inhibited by the metabolism of ethanol?

Answer 23

→ Acetyl CoA, NADH and ATP are formed which inhibits glucose metabolism by inhibiting PFK and pyruvate dehydrogenase
→ NADH inhibits the TCA cycle
→ Acetyl CoA results in ketone body formation and stimulation of fatty acid synthesis
→ Fatty acids are esterified to TG to transport as VLDL

Question 24

What does the second route of metabolism of ethanol involve?

Answer 24

→ Oxidation of ethanol by members of cytochrome P450 enzymes

Question 25

What does the MESO system use?

Answer 25

→ NADPH which is needed for the synthesis of antioxidant glutathione

Question 26

What happens to acetaldehyde with excess alcohol intake?

Answer 26

→ Acetaldehyde builds up

Question 27

What happens in the liver if acetaldehyde builds up?

Answer 27

→ Reduction in secretion of both serum protein and VLDL

Question 28

What can acetaldehyde enhance?

Answer 28

→ Free radical production

→ Leads to tissue damage such as inflammation or necrosis

Question 29

How can cirrhosis cause death?

Answer 29

→ Ammonia accumulates resulting in neurotoxicity, coma and death

Question 30

What are xenobiotics?

Answer 30

→ Compounds with no nutritional value
→ Plant metabolites
→ Drugs
→ Food additives

Question 31

What compounds can be excreted easily in the urine?

Answer 31

→ Water compounds

Question 32

What is the livers aim with xenobiotics?

Answer 32

→ Make them harmless

→ More readily disposed of

Question 33

What are the three phases of xenobiotic metabolism?

Answer 33

→ Oxidation
→ Conjugation
→ Elimination

Question 34

What does Phase I of xenobiotic metabolism do?

Answer 34

→ Oxidation is the most common modification there is also hydroxylation and reduction
→ Modification increases solubility
→ It introduces functional groups which enable participation in further reactions

Question 35

Where are P450 enzymes found?

Answer 35

→ In the endoplasmic reticulum

Question 36

What kind of proteins are P450 enzymes?

Answer 36

→ Haem proteins that are related to mitochondrial enzymes

Question 37

What are P450 enzymes inducible by?

Answer 37

→ Their own substrates

Question 38

Describe Phase II of xenobiotic metabolism

Answer 38

→ Modified by the addition of groups such as
→Glutathione
→ Glucuronic acid
→ Sulphate

Question 39

What does modification in Phase II do?

Answer 39

→ Increases solubility and targets them for excretion

Question 40

Why is drug metabolism important?

Answer 40

→ Part of the bodies natural defences
→ 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

Question 41

What do statins inhibit and what are they degraded by?

Answer 41

→ HMG- CoA reductase

→ Degraded by CYP3A4

Question 42

What is aflatoxin produced by and what are its effects?

Answer 42

→ Produced by the fungus aspergillus flavus
→ Aflatoxin is activated by P450 leading to epoxide formation
→ Hepatocarcinogenesis occurs