Topic 68 - Thermogenesis at the cellular level

Question 1

Words to include

Answer 1

• Increase heat production at a cellular level:
  
  • Mitochondrial heat production in brown adipose
  • Fish experiment
    
    • Heating cells differentiated from muscle cells

Cellular level: brown adipose

• Thyroxine
• Thermogensis
• Uncoupling of ATP synthesis in brown adipose tissue
• UPC thermogenin
  
  • Uncoupling protein
  • Produced in response to thyroid hormones
• Epinephrine
  
  • β-receptor
  • cAMP
  • PK-pathway
  • Generates free fatty acids in cells → opens thermogenin channel
    
    • Transparent to protons
• O₂ & H₂ → H₂​O
  
  • Avoiding respiratory chain

Cellular level: heater cells, futile cycle

• Thermogenin pathway
  
  • Only significant in species (or young animals) with large amounts of brown adipose tissue
• Ca²⁺ pump of sarcoplasmic reticulum
  
  • Ø muscle contraction
• Heater cells
  
  • Modified muscle cells
• Modified ryanodine receptor
  
  • Lekage of Ca²⁺ from SR
  • Ca²⁺ pump activated → high heat production
• Futile cycle
  
  • Skeletal muscle increases Ca²⁺ pump activity with other cation pumps
    
    • Na⁺ permability ↑
      
      • Na⁺/K⁺ pump ↑

Maligant hyperthermia

• Swine disease
  
  • Inherited on a single locus:
    
    • H antigen
    • Phospho-hexo-isomerase (PHI)
    • Defective ryanodine receptor
  • Result:
    
    • ​Stress sensitivity
    • Pathological hyperthermia
• Muscle is an organ of thermogenesis

Question 2

Topics to include in the essay

Answer 2

1. Accepted basic mechanisms
   
   • Brown adipose tissue (mitochondrial heat production)
   • Fish experiment (heating cells differentiated from muscle cells)
2. Brown adipose
3. Heater cells, futile cycle
4. Malignant hyperthermia

Question 3

What are the mechanisms which increases the heat production at a cellular level?

Answer 3

1. Mitochondrial heat production in brown adipose tissue
2. Fish experiment
   
   • ​Heating cells differentiated from muscle cells may have important thermogenic functions all around the body

Question 4

Brown adipose

Answer 4

• Theorie: effects of thyroxine upon the thermogenesis led to the conception of uncoupling of ATP synthesis in brown adipose tissue
• UCP thermogenin (uncoupling protein) is produced as a response to thyroid hormones
  
  • ​Settes in the inner membrane of mitochondria
• Epinephrine (β-receptor cAMP, PK-pathway) generates free fatty acids in the cells → opens thermogenin channel and becomes transparent to protons
• O₂ and H₂ → H₂O
  
  • ​Avoiding respiratory chain, and there is no synthesis of ATP, just heat production

Question 5

Heater cells & futile cycle

Answer 5

• Fish experiment
• Thermogenin pathway can only significantly assist heat production in species (or young animals) with a large amount of brown adipose tissue
• The most effective way of cellular thermogenesis:
  
  • Operating the Ca²⁺ pump of the sarcoplasmic reticulum without muscle contraction
  • The heater cells are modified muscle cells with very few contractile elements, but their SR is developed and they have a lot of mitochondria
  • A modified ryanodine receptor allows lekage of Ca²⁺ from SR → activates Ca²⁺ pumps → high heat production
• Futile cycle:
  
  • In mammals, the skeletal muscles increases the Ca²⁺ pump activity (heat production) due to thyroxine and epinephrine stimulation
  • This is also possible with other cation pumps:
    
    • ​Na⁺ permability ↑ → function of Na⁺/K⁺ pump ↑

Question 6

Maligant hyperthermia

Answer 6

• Disese of swine
  
  • Hleps to clarify the thermogenic role of Ca²⁺ pumping proteins of the SR membrane
• Inherited on a single locus:
  
  • ​H antigen
  • Phospho-hexo-isomerase (PHI)
  • Defective ryanodine receptor
• Result:
  
  • Stress sensitivtity
  • Pathological hyperthermia
• This phenomenon proves the fact that the muscle is an organ of thermogenesis