Uncoupling proteins (UCP)

Uncoupling proteins (UCP)

By: AMEER AZEEZ & ADIL SULAIMAN

In living cells, adenosine triphosphate (ATP) can release the energy that is necessary for life by donating one or two phosphate groups, leaving adenosine diphosphate (ADP) or adenosine monophosphate (AMP), respectively. However, energy storage in the form of ATP is limited and, therefore, ATP has to be resynthesised continuously in the mitochondria..

Uncoupling proteins (UCP)

To resynthesize ATP from ADP, substrates such as fat, carbohydrate and proteins are metabolised, resulting I n the production of NADH and FADH2. Subsequently, NADH and FADH2 can be oxidised to NAD+, FAD and H+ in the respiratory chain

Uncoupling proteins (UCP)

According to the hypothesis of Mitchell (Mitchell, 1966), the protons are transported to the cytosolic side of the inner mitochondrial membrane by a series of reactions. This eventually generates a proton gradient across the membrane, which causes protons to flow back across the inner mitochondrial membrane through a so-called F0F1-complex. The energy thus generated is used by ATPase to transform ADP into ATP. In this way, substrate oxidation is coupled to the formation of ATP.

Uncoupling proteins (UCP)

The coupling between substrate oxidation and ATP formation is not 100 % efficient. The proton gradient, which is built up by the oxidation of substrates, can be reduced by the proton leaks, thereby diminishing the efficiency of ATP synthesis from substrate oxidation and thus dissipating energy as heat. The mechanism by which proton leaks reduce the proton gradient is not completely understood, but it has been proposed that uncoupling proteins (UCPs) are involved.

Uncoupling proteins (UCP)

The uncoupling proteinThe mitochondrial respiration process generates a proton gradient across the mitochondrial inner membrane that establishes th electrochemical potential which is mainly used for ATP synthesis. However, not all of the energy available in the electrochemical gradien is coupled to ATP synthesis. Some of the energy is consumed by “proton leak” reactions, by which protons pumped into the inner membrane space flow back into the matrix through proton conductance pathways in the inner membrane that bypass the ATP synthas

• UCP1: is the first to be identified in brown adipose tissue

• UCP2 is ubiquitously expressed• UCP3 exists solely in skeletal muscle and

the heart• UCP4 and• BMCP1 (brain mitochondrial carrier

protein-1, or UCP5 are predominantly expressed in the central nervous system

Mitochondrial uncoupling is mediated mainly by uncoupling proteins (UCPs), among those:-

UCPs are anion carriers across the mitochondrial inner membrane, which bring protons back into the mitochondrial matrix. In addition, UCP1 dissipates redox energy and thereby provides heat to the animal. UCP2 decreases the production of reactive oxygen species [12].Furthermore, it has been suggested that brain-specific UCP4 and UCP5 play a role in apoptosis in thebrain

UCP1, alsocalled thermogenin, is responsible for the heat production in the brown adipocytes of mammals. UCP1 is activated by fatty acids. Brown fat, unlike the more abundant white fat, uses almost 90% of its respiratory energy for thermogenesis in response to cold in the neonate, and during arousal in hibernating animals.

However, humans appear to have little brown fat (except in the newborn), and UCP1 does not appear to play a major role in energy balance. [Note: Other uncoupling proteins (UCP2,UCP3) have been found in humans, but their significance remains unclear.]

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