68. Thermogenesis at the cellular level Flashcards
Thermogenesis at the cellular level
- The mitochondrial heat production found in the brown adipose tissue may probably be effective in other tissues as well. 2. Based on fish experiments it is presumed that modified “heating cells” differentiated from muscle cells may have important thermogenic functions all around the body.
Cellular level: brown adipose
The first uncoupling was observed in the brown adipose tissue. The essence of this process is that a protein (32 kDa, Thermogenin, uncoupling protein, UCP ), which settles in the inner membrane of mitochondria is produced as a response to thyroid hormones. By the effect of epinephrine (beta receptor - cAMP, PK-pathway) free fatty acids are generated in the cells, which open the thermogenin channel: it becomes transparent to protons. Thus oxygen and hydrogen are united to water avoiding the respiratory chain and there is no synthesis of ATP, just heat production.
Cellular level: brown adipose (picture)
Cellular level: heater cells, futile cycle
The search for the special “heater-cells” resulted in the recognition that the most effective - and probably the most common - other way of cellular thermogenesis is operating the calcium pump of the sarcoplasmatic reticulum without muscle contraction.
The heater cells are modified muscle cells, which have very few contractile elements but their SR is very much developed and they have many mitochondria.
A modified ryanodine receptor allows the leakage of calcium from the SR, which then continuously activates the calcium pumps, leading to high heat production.
The modified muscle cells in fish are the heater cells. It has been proved that in mammals the skeletal muscle increases the calcium pump activity (heat production!) due to epinephrine and thyroxine stimulation. This is possible with other cation pumps: e.g. increasing of sodium permeability gears up the function of the sodium/potassium pump. Since this time the pump is “abused” it is usually called “futile cycle” process.
The thermogenin pathway can assist significantly the heat production in only those species….
The thermogenin pathway can assist significantly the heat production in only those species -or young animals -, which have large amount of brown adipose tissue. (E.g. small mammals) •
Malignant hyperthermia
Molecular biological examinations of the malignant hyperthermia - a well known disease of swine- helped to clarify the thermogenic role of calcium pumping proteins of the SR membrane.
The lysine instead of arginine at one point of the protein makes these channels leaky to calcium.
This results in an intensive pumping back of calcium into the SR, which causes extremely high heat production; this leads to a severe hyperthermia that causes heat-death (especially if the animal is exposed to stress situation too - epinephrine effect). • This phenomenon proves the fact that the muscle - with its mass and molecular mechanisms - is not only a contractile tissue but the organ of thermogenesis too.
The H antigen
The H antigen, the phospho-hexoisomerase (PHI) and the defective ryanodine receptor are inherited on a single locus: – stress sensitivity – pathological hyperthermia
The defective ryanodine channel SR is coinherited with the H antigen.
Hyperthermia
Hyperthermia is a condition where an individual’s body temperature is elevated beyond normal due to failed thermoregulation.
