Uncouplers long-chain fatty acids

The properties are as follows, (i) The activity of the protein (i.e. the inward transport of protons) is inhibited by ATP. (ii) The activity of the protein is increased by the presence of long-chain fatty acids, since they relieve the ATP inhibition, (iii) When mitochondria, isolated from brown adipose tissue, are incubated in the presence of fatty acids, there is a sharp increase in the rates of electron transfer, substrate utilisation and oxygen consumption, whereas the rate of ATP generation remains low. These studies indicate that the rate of proton transport, by the uncoupling protein, depends on the balance between the concentrations of ATP and fatty acids, (iv) In adipocytes isolated from brown adipose tissue, the rate of oxygen consumption (i.e. electron transfer) is increased in the presence of catecholamines. 

Figure 9.29 Control of heat production in brown adipose tissue. Catecholamines increase cyclic AMP concentrab on which stimulates triacylglycerol lipase which increases the long-chain fatty acid level, which increases the fluxes through P-oxidation and the Krebs cycle, and the activity of the uncoupling protein. Uncoupling decreases the ATP concentration which further increases the activity of the uncoupling.

Long-chain fatty acids also cause uncoupling. The mechanism appears complex, but seems to be distinct from either simple membrane disruption or a classical protonophoric effect, and appears to require the involvement of active transporters [9, 14, 19, 21-24). 

Schonfeld, P., Schild, L., Kunz, W. (1989). Long-chain fatty acids act as protonophoric uncouplers of oxidative phosphorylation in rat liver mitochondria. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 977(3), 266-272. 

A long-chain unsaturated fatty acid found in plants, especially rapeseed and mustard seed oil. Uncouples oxidative phosphorylation in rat heart mitochondria cardiac damage in rats. Effects in man not reported. 

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