Question 4

College Answer

This question relates to basic hepatic physiology and is well described in the recommended texts. The mark allocation and division of time was indicated in the question. Better answers used the categorisation in the question as an answer structure. Many candidates gave a good description of beta oxidation, the formation of Acetyl Co A and ketone synthesis. A description of the synthesis of cholesterol, phospholipids, lipoproteins and fatty acid synthesis from proteins and carbohydrates mainly using glycogen, glucose and lactate also received marks. Candidates seem to have a better understanding of fat and glucose metabolism than protein metabolism. Higher scoring candidates appreciated the anabolic and catabolic processes of each component.

Discussion

As a sterol, cholesterol probably does belong in the "fat" category, but the way the question reads might seem to suggest that mainly dietary macronutrients were being asked about. From seeing the stem and the breakdown of marks, a casual reader would not immediately understand that phospholipid synthesis or lactate metabolism would be an essential part of the answer. What follows is an attempt to answer the question as it was written (whereas the college comments describe the answer to a somewhat different question).

• Carbohydrate metabolism in the liver:
  • Uptake: Glucose enters via the insulin-insensitive GLUT2 transporter, and is rapidly phosphorylated into glucose-6-phosphate
  • Biotransformation:
    • Post-prandial glycogen synthesis from glucose
    • Post-prandial fatty acid sand triglyceride synthesis from glucose
    • Fasting gluconeogenesis (from fatty acids or amino acids)
  • Storage: As glycogen (75-100g) and as triglycerides (less than 5% of liver mass)
  • Release: Glycogenolysis and liberation of glucose by glucose-6-phosphatase
• Lipid metabolism in the liver:
  • Uptake​​​​​​​: the liver is able to take free fatty acids and chylomicron remnants from the bloodstream by receptor-mediated endocytosis
  • Biotransformation:
    • Excess dietary glucose can be transformed into free fatty acids
    • ​​​​​​​Free fatty acids can be transformed into triglycerides or ketones
    • Ketones are exported as an alternative metabolic fuel between meals
    • Triglycerides can be stored in the liver itself, or exported as lipoproteins
    • Free fatty acids are also preferentially used as fuel by hepatocytes (where they are metabolised by β-oxidation to create ATP)
  • ​​​​​​​Storage: ​​​​​​​​​​​​​​Triglycerides can be stored in the liver, but this is undesirable and can lead to pathological changes. Adipose tissue is a better storage site.
  • Release:  The liver exports triglycerides, in the form of VLDL, which are:
    • used as a source of free fatty acids by the tissues, and
    • used to transporting lipids to adipose tissue for storage
• Protein metabolism in the liver:
  • ​​​​​​​Uptake​​​​​​​​​​​​​​: amino acids and proteins, by Kupffer cells and hepatocytes
  • Biotransformation:
    • Circulating proteins are degraded into constituent amino acids
    • Non-essential amino acids can also be generated de novo
    • Amino acids can be 
      • Deaminated or oxidised into carbon skeletons, and used as a source of metabolic fuel
      • Transaminated and transformed into other amino acids
  • Amino acids and proteins are not stored in the liver
  • Their deamination produces ammonia as a byproduct

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