Electron Transport Chain

The electron transport chain is the  process that culminates in the synthesis of ATP when the four protein complexes that make up the electron transport chain combine redox events to create an electrochemical gradient. The mitochondria are the structures that carry out photosynthesis and cellular respiration. In the former, the disintegration of organic molecules causes the release of energy along with the electrons. In the latter, light-induced electron entry into the chain is followed by the release of energy, which is then used to produce carbohydrates.

Read this blog further to get a quick overview of this important topic for biochemistry and ace your NEET PG exam preparation.

Tool of Oxidative Phosphorylation

It is a tool of Oxidative Phosphorylation, that is a type of catabolism. In catabolism, the breakdown of  biomolecules into simpler substances occurs by breaking covalent linkages. Whenever covalent linkages get broken, energy gets liberated. In the case of oxidative phosphorylation, the liberated energy does not get trapped directly in the form of ATP. Rather it is trapped in the form of reducing equivalents like NADH or FADH 2. 

When NADH and FADH 2 oxidized, they lose electrons, and these electrons then get collected NADH or FADH 2 and transport to the electron transport chain. Electron transport chains in a complex way liberates energy. Then this energy is used for phosphorylating ADP to form ATP. This chain acts as a tool for oxidative phosphorylation. The fact is that for something to get into the electron transport chain it must be either NADH or FADH 2 and not NADPH. Because NADPH cannot give rise to energy. Glycolysis happens in cytoplasm and in glycolysis, for every molecule that gets into this pathway, 2 NADH get generated. Those 2 NADH will have to be transported from cytoplasm to mitochondria. NADH cannot cross the mitochondrial membrane so a shuttle is going to be used. There will be two shuttles- Malate shuttle and glycerol phosphate shuttle. 

What is the Malate shuttle?

In malate shuttle NADH is transported in the form of malate. For this purpose, two enzymes will be used- cytoplasmic malate dehydrogenase and mitochondrial malate dehydrogenase. Cytoplasmic malate dehydrogenase acts upon NADH, gets electrons from it, and uses that electron to reduce its substrates. The substrate is oxaloacetate, it accepts electrons and converts them to malate. Electrons get hidden in the form of malate.  Now the mitochondrial membrane will transport malate from cytoplasm to mitochondria. Once malate reaches the mitochondria, mitochondrial dehydrogenase acts upon malate and converse it into oxaloacetate. During this conversion of malate to oxaloacetate, electrons are taken out again and that electron is given to its coenzyme. Its coenzyme is NAD and after getting this it will become NADH.  This malate shuttle is present all the cells, but 2 exceptions are there. They are white muscle fiber and neurons. They both have glycerol phosphate shuttle. 

Glycerol Phosphate Shuttle

In glycerol phosphate shuttle NADH is transported in the form of glycerol. For this purpose, two enzymes will be used- cytoplasmic glycerol-3-phosphate dehydrogenase and mitochondrial glycerol-3-phosphate dehydrogenase. Glycerol-3-phosphate dehydrogenase acts upon NADH. It will get electrons from it and give these electrons to its substrates. Here the substrate is dihydroxyacetone phosphate which accepts the electron and converts it to glycerol-3-phosphate. Now the electron is hidden in the form of glycerol-3-phosphate.  Carrying electron glycerol-3-phosphate will enter mitochondria. Mitochondrial glycerol-3-phosphate dehydrogenase converts this into dihydroxyacetone phosphate. During this conversion electrons are taken out again and that electron is given to its coenzyme. Its coenzyme is FAD and after getting this it will become FADH2.  This FADH2 will enter the electron transport chain. The major difference between malate shuttle and glycerol phosphate shuttle is that in malate shuttle, cytoplasmic NADH will become mitochondrial NADH and in glycerol phosphate shuttle cytoplasmic NADH will become mitochondrial FADH2. So, there will be loss of ATP because NADH would give 2.5 ATPs and if it is going to become FADH2 it will give only 1.5 ATPs. There is a difference of 1 ATP for every NADH that is getting transported this way. In glycolysis, from every molecule of glucose, 2 NADH is obtained. To transport both these NADH, two ATPs will be missing.

What are Complexes of electron transport chain?

All complexes of the electron transport chain are made up of cytochrome heme proteins. Heme proteins have heme in the center and are surrounded by protein or polypeptide genes. Every heme will have metal in its center surrounded by 4 pyrrole rings. This central metal can be the ion found in hemoglobin or myoglobin or it can be magnesium found in chlorophyll.

Non-cytochrome heme proteins: the central atom cannot shift between their states of oxidation. For example: hemoglobin and myoglobin. In hemoglobin, for transformation of oxygen the central atom must be Fe+2. When this Fe+2 becomes Fe+3 it becomes methemoglobin. Hemoglobin is a non-cytochrome heme protein. When the metal in the center can shift between its various oxidation states, it will become cytochrome heme proteins. If the metal in the center can shift between its various oxidation states, then only it can help in electron transport. For example, complex 1 is the cytochrome heme protein with the central atom Fe+2. But this atom can shift to Fe+3 and then come back to Fe+2.

 When complex 1 accepts electrons from NADH, Fe3+ will become Fe2+. When this complex donates its electron to another complex, it will be back to its Fe3+ form. All complexes have ions in the center, only one exception is there, that is complex 4. Complex 4 is cytochrome a and a3 and has copper in the center. There is one complex that does not have cytochrome heme proteins is the mobile complex Q.

There are 5 stationary complexes and 2 mobile complexes

5 stationary complexes are named in Roman letters:

Complex I

• It is NADH linked dehydrogenase.
• Electrons from NADH will enter into electron transport chain through complex 1

Complex II

• Long back we used to call complex II as FADH2 linked dehydrogenase and electrons from FADH2 will enter into the electron transport chain through complex II.
• Now we know that complex II is a succinate dehydrogenase.

Complex III

• Complex III is cytochrome b and c1

Complex IV

• Complex IV is cytochrome a and a3

Complex V

• Complex V is ATP synthase complex.

2 mobile complexes 

First stationary complex is the ubiquinone/ Q placed between complex I and complex III. The second one is cytochrome C placed between complex III and complex IV. Stationary complexes are placed between mobile complexes because it helps in electron transport. Complex Q takes electrons from complex I and gives them to complex III. Cytochrome C goes to complex III, takes electrons and gives it to complex IV. Direction of transport of electron is, if it is an NADH electron then it will enter from complex I, from complex I it will go to complex Q, from complex Q it will go to complex III, from complex III it will go to cytochrome C, from this it will go to complex IV and finally will be accepted by O2. The final acceptor of the NADH electron is O2. If is an FADH2 electron, it will enter into electron transport chain through complex II, from complex II it goes to complex Q, from complex Q it will go to complex III, from complex III it will go to cytochrome C, from this it will go to complex IV and finally will be accepted by O2. Apart from succinate dehydrogenase, there are few other FADH2 linked dehydrogenase such as Acyl COA dehydrogenase (enzyme of fatty acid oxidation), mitochondrial glycerol-3-phosphate dehydrogenase, Other than succinate dehydrogenase, the other 2 dehydrogenases will directly enter from complex Q and will follow the same direction. 

Production of ATP from ETC complexes was given by mitchell chemiosmotic theory. According to this theory, all these complexes are arranged in an increasing order of redox potential (measure of ability to reduce). Redox potential means Ability to get reduced is directly proportional to state of oxidation. More the substance is reduced, the higher the energy it contains.Oxidation and energy levels will be inversely proportional. Such that these complexes are arranged in a decreasing order of energy levels.

The energy that is liberated during the electron transport from higher energy level to lower energy level is used to pump hydrogen atoms from the matrix to outside the inner mitochondrial membrane.

This green ring is the inner mitochondrial membrane. All these complexes are arranged in the inner side of the inner mitochondrial membrane. After the hydrogen atom accumulates outside the Inner mitochondrial membrane, these hydrogen ions will find their way through the Fo component of ATP synthase complex. This complex V has two subunits, one is Fo subunit and the other one F1 subunit.  Fo is an ion channel through which hydrogen ions can move and F1 is actual ATP synthase enzyme. Hydrogen ions move from the higher concentration region to lower concentration region and that will liberate energy. When hydrogen ions move through the Fo component of ATP synthase complex, energy is liberated, and that energy is finally used for phosphorylating ADP to form ATP. This is how ETC helps in ATP production.

Also Read : LIPIDS: CLASSIFICATION, PUFAS, LIPOPROTEINS, KETONE BODY SYNTHESIS & UTILIZATION

What are the Inhibitors of Electron chain transport?

The electron transport between complex I and complex Q is inhibited by amobarbital, piericidin A, rotenone. Complex II or Q is inhibited by malonate. The electron transport between complex II and complex Q is inhibited by TTFA and carboxin. The electron transport between complex III and complex C is inhibited by BAL and antimycin. 

The electron transport between complex IV and oxygen is inhibited by hydrogen sulfide, cyanide, and carbon monoxide. Cyanide causes histotoxic hypoxia, does not matter how much oxygen is available, tissues will not be able to extract oxygen because electron transport is inhibited by cyanide. The major mechanism by which carbon monoxide exhibits toxicity is that carbon monoxide exhibits very high affinity to Fe2+ of hemoglobin so it displaces oxygen.  The oxygen carrying capacity of hemoglobin reduces and this is called anemia. So, carbon monoxide causes anemic hypoxia. Any electron transport inhibitor will cause histotoxic hypoxia.

Uncouplers 

The major function of ETC is that it couples oxidation of fuel with phosphorylation of ADP to form ATP. The uncoupler uncouples oxidation from phosphorylation. It means oxidation of fuel will be done continuously without phosphorylation.

Effects of uncouplers 

The first effect of uncoupler will be that there will be no ATP production.  There is Increase in the rate of heat production and there is Increase in the rate of oxidation of all the fuels so it will increase basal metabolic rate.

Definition of uncouplers

All uncouplers are ion channels and they get inserted into the inner mitochondrial membrane. Through these ion channels, hydrogen ions will bypass. Because hydrogen ions do not go through Fo components, ATP will not be produced. Here also hydrogen ions move from regions of higher concentration to regions of lower concentration, so the energy will be liberated out as heat.

Types of Uncouplers

Two types of uncouplers are there, physiological uncouplers and artificial uncouplers. 

Physiological uncouplers

They include thyroxine and brown adipose tissue. Thyroxine causes upregulation of uncoupler proteins in the inner mitochondrial membrane through which hydrogen ions by pass, no ATP, no heat production occurs that is why thyrotoxicosis presents with heat intolerance and that is why hypothyroidism presents with cold intolerance. For want of ATP, more and more fuels will be oxidized in the presence of thyroxine. Brown adipose tissue is of brown color because it has got numerous mitochondria and in all these inner mitochondrial membrane, uncoupler proteins are inserted. Through these uncouplers, hydrogen ions by pass that is why no ATP production and only heat production will be there. Brown adipose tissue helps in heat production and they are considered as a mechanism for non-shivering thermogenesis neonates and hibernating animal. Neonates do not exhibit shivering, but they have to generate heat. At the time of birth, we all born with adequate amount of brown adipose tissue. For example, the interscapular region has lots of brown adipose tissue, in the neonatal period that helps in heat production. As age progresses, the brown adipose tissue regress. In some people, this brown adipose tissue is retained and that is quite fortunate. That means any fuel they will intake will be oxidized, and energy will be liberated as heat. It doesn't couple to ATP production and there will be no anabolism and wright gains.

Artificial Uncouplers

Artificial uncouplers include 2,4 Dinitrophenol, valinomycin, nalinomycin, and nijaricin. These 4 were once tried as anti-obesity drugs. In the presence of these uncouplers, all the fuels will be oxidized, and energy will be liberated as heat, no ATP production, and no anabolism. Most of them are presented as increased heat production and many of them are posterior subcapsular cataracts, they all withdrew from the market.

Oligomycin

Oligomycin acts by inhibiting the Fo component of ATP synthase complex. It is denoted by Fo to show that it is inhibited by oligomycin. In the presence of oligomycin, hydrogen atoms will not enter into mitochondria through ATP synthase complex. So there will be no ATP synthesis. The difference between this and other uncouplers is that In other uncouplers hydrogen a ions somehow manage to get into the matrix. As long as hydrogen ions stay within the matrix, oxidation of fuel will happen continuously. In the presence of uncoupler, only phosphorylation is arrested but oxidation happens continuously. In the presence of oligomycin which inhibits the Fo component of ATP synthase complex, there is no way hydrogen ions can get into the matrix. Without hydrogen ions, electron transport will stop. When electron transport stops, oxidation of fuel will also stop. The only difference between uncouplers and oligomycin is that in oligomycin not only phosphorylation but also oxidation are arrested. 

This is everything that you need to know about electron transport chain  for your biochemistry preparation. For more interesting and informative blog posts like this download the PrepLadder App and keep reading our blog!