N1i / 20B04 / 15A18: Metabolic role of liver

20B04: Exam Report

Outline the role of the liver in the metabolism of fat (1⁄3 marks), carbohydrate (1⁄3 marks) and proteins (1⁄3 marks)

54% of candidates passed this question.

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.

15A18: Exam Report

Outline the role of the liver in the metabolism of fat (1/3 of marks), carbohydrate (1/3 of marks) and proteins (1/3 of marks).

50% of candidates passed this question.

Most candidates seemed not to have thought about this before and so collated information from answers about insulin and glucagon, and starvation. Many added information about absorption and digestion which was not required.

Metabolic functions of the liver form part of the “standard list” of functions of the liver yet few details could be provided beyond that. It was expected answers would detail the central role of the liver as a “glucostat” and its role in glucose utilization. It has two main roles in lipid metabolism, the synthesis of fatty acids and the partial oxidation of fatty acids to ketone bodies. The liver also plays a central role in protein catabolism and anabolism. It plays a major role in the breakdown of amino acids gluconeogenesis and protein synthesis. The liver also releases amino acids into the blood for utilization by peripheral tissues.

N1i / 20B04 / 15A18: Outline the role of the liver in the metabolism of fat (1/3 marks), carbohydrate (1/3 marks) and proteins (1/3 marks)

Definitions

Metabolism = chemical ∆ in a cell when there is a breakdown + synthesis of stored E

Liver = large pool of cells with high metabolism, sharing substrates & E from one metabolic system to another

Carb Metabolism

  1. GLUCOSTAT
  2. GLYCOGEN STORAGE & RELEASE
  3. GLUCONEOGENESIS

1) Glucostat → liver is essential for maintaining normal BGL

  • Feeding → glucose uptake by hepatocytes
  • Fasting → release of glucose into blood from stores or synthesis of glucose from non-carb precursors
  • Balance b/w glucagon & insulin

2) Glycogen Storage & Release

  • Stores 100g glycogen
  • Dietary glucose is taken up by intestinal cells by active transport → Portal Venous Circulation
  • Glucose taken up by hepatocytes require NO ENERGY as it is converted to G6P immediately to maintain a diffusion gradient
  • Glycogen is formed from G6P
  • Amount stored is controlled by glycogen synthetase & glycogen phosphorylase
  • Glucagon → secreted by ↓[glucose] → stimulates glycogen breakdown → releases glucose

3) Gluconeogenesis

  • Liver can convert non-carb precursors (amino acids, lactate, pyruvate, glycerol) into glucose via gluconeogenesis
  • Stimulated by glucagon
  • Glucose enters glycolysis → Kreb’s → ETC → ATP

Fat Metabolism

  1. FAT STORAGE
  2. B-OXIDATION
  3. KETOGENESIS
  4. FA & CHOLESTEROL SYNTHESIS

1) Fat Storage

  • Liver & AT have ↑[Lipoprotein Lipase]
  • Hydrolyses chylomicrons → TAGs → FAs + glycerol
  • Diffuse into hepatocytes + reform TAGs for storage

2) Lipolysis & B-Oxidation

  • To obtain E from fat : TAGs → Glycerol + FFAs
  • Stimulated by HORMONE SENSITIVE LIPASE
  • FAs oxidised by β-oxidation in cytoplasm to Acetyl CoA → mitochondria → Krebs → ETC → ATP

3) Ketogenesis

  • Ketones are an alternative E source
  • Excess acetyl CoA/starvation stimulates ketone production
  • Ketones freely diffusible → provide E for brain

4) Fa & Cholesterol Synthesis

  • Excess Acetyl CoA → converted into TAGs & stored in hepatocytes / AT
  • TAGs can be synthesised from carb & protein precursors
  • When glycogen stores are full; Glucose → Acetyl CoA → TAGs → transported in VLDL to AT for storage
  • Excess amino acids are deaminated → form ketoacids
  • Ketoacids can either be oxidised for E or form Acetyl CoA for TAG synthesis & storage
  • Endogenous cholesterol synthesis is controlled by HMG-CoA enzyme
  • Synthesised entirely from multiple Acetyl CoA molecules
  • 80% of cholesterol is used for formation of Bile

Protein Metabolism

  1. PROTEIN SYNTHESIS
  2. A-ACID UTILISATION
  3. UREA SYNTHESIS

1) Protein Synthesis

  • Amino acids are taken up by liver from portal circulation
  • Liver synthesises albumin, globulin, haptoglobins, a1-antitrypsin, antithrombin III, clotting factors, CRP, α1 glycoprotein

2) Amino Acid Utilisation

  • A-acids degraded by transamination, deamination, decarboxylation
  • Produces Acetyl CoA, oxoglutarate, succinyl CoA, oxaloacetate & fumarate → enters Krebs

3) UREA

  • NH3 is an end product of a-acid degradation
  • NH3 enters ornithine cycle → converted to urea for excretion in urine