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Biology: Uncoupling Proteins Essay

2720 words - 11 pages

Since its’ discovery in the late 1970s, uncoupling proteins have roused excitement among cellular biologists due to its’ central role in energy dissipation. Subsequently, the uncoupling effect as well as the physiological role of the first uncoupling protein, UCP1, is well established when researchers at the time, were devoting their focus on the thermogenic capacity of brown adipose tissue or BAT. They were looking specifically at mitochondria in this tissue to define fat storage mechanisms in response to dietary restriction and temperature [1]. BAT comprises of numerous specialized fat cells with a function in generating heat and balancing energy. Cold-blooded animals and hibernating ...view middle of the document...

The metabolic pathway that mitochondria in cells use to reform ATP via the oxidation of nutrients is known as oxidative phosphorylation. ATP is known as the molecule that supplies the energy needed for metabolism. This pathway is highly efficient at releasing energy rather than the alternative pathway known as glycolysis. Glycolysis is the formation of pyruvate from glucose in the cytoplasm. When it enters the mitochondrial matrix, pyruvate is converted into acetyl-CoA which then enters the Krebs cycle.
Oxidative phosphorylation is a process by which electrons are transferred from electron donors to electron acceptors as is the case with oxygen in redox reactions. The energy released form this reaction forms ATP. The redox reactions are conducted by a series of protein complexes located in the inner mitochondrial membrane in eukaryotes. These protein complexes are known as electron transport chains, where there are five central ones involved in the reaction.
When electrons flow through the electron transport chain, energy is released which transports protons across the inner mitochondrial membrane. The potential energy is stored as a pH gradient and electrical potential across this membrane. ATP synthase, a large enzyme, taps into this energy and allows protons to flow across the membrane and down the gradient. ATP synthase then uses the energy to generate ATP from ADP in a phosphorylation reaction. The free radicals produced such as superoxide and hydrogen peroxide leads to propagation of free radicals.
The respiration that occurs in the mitochondria generates a proton gradient that establishes an electrochemical potential in the mitochondrial inner membrane. The electrochemical gradient is mainly used for ATP synthesis. In saying that, however, the energy that is available in the electrochemical gradient is not always coupled with ATP synthesis. A reaction known as ‘proton leak’ occurs and uses some of this energy. ‘Proton leak’ is a process whereby protons that are pumped into the inner membrane space of the mitochondria flow back into the matrix via proton conductance pathways that are contained in the inner membrane and thus bypass the ATP synthase[3-6]. Subsequently, the energy that is derived from this metabolic oxidation process is dissipated as heat. This ‘inefficiency’ of the mitochondria is termed mitochondrial uncoupling and is physiologically important as it accounts for 20% of basal metabolic rate [5, 7].
Mitochondrial uncoupling is facilitated by UCPs. UCPs are characterized as the anion carriers across the mitochondrial inner membrane which transport protons back into the mitochondrial matrix. The first to be discovered was UCP1 which was found in brown adipose tissue by Bouillaud et al., in 1985. UCP2 was then found and identified as being ubiquitously expressed [8] and UCP3 is found to exist solely in the heart and skeletal muscle [9]. UCP4 and UCP5 were discovered and suggested to be brain-specific as they localise in the...

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