Lipid and ketone body metabolism

Question 1

What are the 3 types of lipids?

Answer 1

• Triacylglycerols
• Fatty acids
• Ketone bodies

Question 2

Fatty acid derivatives (4 things)

Answer 2

• Triacylglycerols (fuel storage & insulation)
• Fatty acids (fuel molecules)
• Phospholipids (membrane and lipoprotein components)
• Eicosanoids (local mediators, signalling)

Question 3

Hydroxy-methyl-glutaric acid derivatives (4 things)

Answer 3

• Ketone bodies (water soluble fuel molecules)
• Cholesterol (membranes and steroid hormone synthesis)
• Cholesterol esters (cholesterol storage)
• Bile acids and salts (lipid digestion)

Question 4

Triacylglycerol key points (5 things)

Answer 4

• Hydrophobic
• Stored in anhydrous form
• Stored in adipose tissue
• Utilised in prolonged exercise, starvation, pregnancy
• Storage/mobilisation under hormonal control

Question 5

What is the esterification of triacylglycerols promoted by?

Answer 5

Insulin

Question 6

What is the lipolysis of triacylglycerols promoted by (5 things)?

Answer 6

• Glucagon
• Adrenaline
• Cortisol
• HGH
• Thyroxine

Question 7

Dietary triacylglycerol metabolism (3 things)

Answer 7

• Stage 1
• GI tract
• Extracellular: pancreatic lipase, bile salts and colipase

Question 8

Fatty acids key points (5 things)

Answer 8

• Converted back to triglycerides in GI tract
• Packaged into lipoprotein particle, chylomicron
• Released into circulation via lymphatics
• Carried to adipose tissue and stored as triglycerides
• Carried to tissues as albumin-fatty acid complex when needed

Question 9

Fatty acid activation (3 things)

Answer 9

• In cytoplasm
• Linked to CoA by action of fatty acyl CoA synthase
• Activated fatty acids don’t readily cross inner mitochondrial membrane

Question 10

Carnitine shuttle (5 things)

Answer 10

• Transports fatty acyl CoA across mitochondrial membrane
• Carnitine converted to acyl carnitine then back again via carnitine acyl transferases (CAT1&2)
• Regulated by AMP, insulin
• Inhibited by malonyl~CoA so fatty acids not used up instantly
• Defects can occur (exercise intolerance, lipid droplets in muscle)

Question 11

Beta oxidation (6 things)

Answer 11

• Recycled through reaction removing a C2 unit until only 2 C remain
• Ultimately generates acetyl~CoA and reducing power (NADH & FADH2)
• Occurs in most tissues and WBC
• Stops in absence of O2
• Regulated by AMP (insulin-liver)
• No direct ATP synthesis

Question 12

Ketone bodies key points (5 things)

Answer 12

• Soluble
• Produced when acetyl CoA is in excess
• Used by peripheral tissues (muscle)
• Alternative fuel to glucose (e.g. brain)
• Acidic

Question 13

Ketosis concentrations key points (4 things)

Answer 13

• Normal concentration is <1 mM
• Starvation is 2-10 mM (physiological ketosis)
• Untreated type 1 diabetes >10 mM (pathological ketosis)
  
  • Sweet smell in breath due to acetone excretion from lungs

Question 14

Ketone body synthesis in liver mitochondria (3 enzymes)

Answer 14

• Synthase
• HMG~CoA reductase
• Lyase

Question 15

What is needed for ketone body synthesis (2 things)?

Answer 15

• Fatty acids for oxidation in LIVER following excess lipolysis in ADIPOSE
• Low plasma insulin:glucagon ratio

Question 16

Control of ketone body production liver (3 things)

Answer 16

• NADH product inhibition
• Catalysed by:
  
  • isocitrate dehydrogenase
  • alpha-ketoglutarate dehydrogenase

Question 17

Ketone body synthesis- fed state (3 things)

Answer 17

• Insulin:glucagon ratio high
• Lyase inhibited and reductase activated
• Cholesterol synthesis (from melavonate)

Question 18

Ketone body synthesis- starvation (3 things)

Answer 18

• Insulin:glucagon ratio low
• Lyase activated and reductase inhibited
• Ketone body synthesis

Question 19

Examples of ketone bodies in body (4 things)

Answer 19

• Acetoacetate
• Beta-hydroxybutyrate ( from acetoacetate)
• Melavonate (in fed state to make cholesterol)
• Acetone (excreted via lungs)