Liver Metabolic Functions

Question 1

Describe the different zones of the acinus of the liver.

Answer 1

Zone 1 - closer to afferent arterioles. Pathways involving respiratory chain activation are found here. i.e. TCA cycle, gluconeogenesis, urea synthesis and production and secretion of bile.
Zone 2 - Intermediate zone between the zones 1 and 3. It carries out ammonia detoxification
Zone 3 - contains anaerobic metabolic pathways as it lies nearer to the terminal hepatic veins. This includes glucolysis, glutamine synthesis, lipogenesis, ketogenesis and xenobiotic metabolism

Question 2

Which enzyme removes TAG from chylomicrons and VLDL. Where is it found?

Answer 2

Lipoprotein Lipase. It is found on the surface of endothelial cells.

Question 3

What is the function of LDL?

Answer 3

To deliver cholesterol to cells to be used in membranes or in the synthesis of steroid hormones.

Question 4

Where do Phase 1 Reactions occur?

Answer 4

In the smooth endoplasmic reticulum of the hepatocyte.

Question 5

What are the components of Bile?

Answer 5

Water, Electrolytes, Phospholipids, Bile Salts or Acids, Bile Pigments, Cholesterol, Heme Waste Products and other substances from blood.

Question 6

What happens when RBCs phagocytose?

Answer 6

At 126 days RBCs are phagocytosed and haemoglobin is released. Haemoglobin is further broken down into haeme, which is converted to bilirubin, globins which are broken down into amino acids and recycled, and iron, which is bound by transferrin and returned to iron stores in the liver or bone marrow.

Question 7

To which protein is Bilirubin (unconjugated) normally bound?

Answer 7

Albumin

Question 8

What molecule picks up unconjugated bilirubin in the liver and presents it to glucaronic acid?

Answer 8

Ligandin

Question 9

Which enzyme causes the conjugation of Bilirubin

Answer 9

UDP-glucuronyl transferase

Question 10

In what ways could metabolic pathways be disturbed?

Answer 10

Congenital deficiency of enzymes
Nutritional deficiency/excess of substrate e.g. cholesterol
Toxic/chemical damage to organelles e.g. paracetamol
Hypoxia/Ischaemic Insult
Secondary to metabolic effects of disease

Question 11

By which mechanisms can you get metabolic dysfunction in inherited diseases?

Answer 11

• Essential product deficit - G6P deficiency (Glycogen Storage type 1 ) can lead to anaemia.
• Precursor accumulation - OTC deficiency (hyperammonaemia) can lead to children having learning difficulties if not acted on quickly.
• Alternative Pathway Activation - amino-acidopathy
• Combinations of the above

Question 12

By which mechanisms can you get metabolic dysfunction in mitochondrial damage?

Answer 12

• Inhibition of the beta-oxygenation of fatty acids - can lead to microvascular steatosis which is common in those who consume large amounts of alcohol.
• Interference with oxidative phosphorylation - leads to insufficient production of ATP
• Impairment of the respiratory chain - leads to excess ROS with lipid peroxidation
• Increase in permeability transition - leads to cell death

Question 13

In what ways can you get toxic damage to the liver?

Answer 13

Mitochondrial Damage
Endothelial damage to hepatic veins
Glutathione depletion and cell death