Mitochondria: Power House of Cell | Biologic Oxidation

Read this article to learn about:- 1. Mitochondria – Power House of Cell 2. Organisation of the Respiratory Chain 3. Transport of Substances Into and Out.

Mitochondria – Power House of Cell:

The mitochondrion has been termed the “Power House” of the cell due to the following reasons:

1. Most of the useful energy derived from oxi­dation within the tissues is captured in the form of the high-energy intermediate, ATP.

2. All the useful energy formed from the oxi­dation of fatty acids and amino acids and virtually all the energy formed from the oxidation of carbohydrates are available in the mitochondrion.

3. For the production of this energy the mi­tochondrion contains the series of cata­lysts known as the respiratory chain which are concerned with the transport of reduc­ing equivalents (Hydrogen and electrons) and with their final reaction with oxygen to form water.

4. Mitochondrion also contains the enzyme systems i.e. the enzymes of β-oxidation and of the citric acid cycle which are re­sponsible for producing the reducing equivalents in the first place.

These relationships are shown in (Fig. 12.16).

Organisation of the Respiratory Chain in Mitochondria:

1. The major components of the respiratory chain are arranged in order of increasing redox potential shown in (Fig 12.17).

2. Electron flow through the chain from the more electronegative components to the more electropositive oxygen. Thus, the redox potential of a component of the chain gives the information regarding the position in the chain.

3. The main respiratory chain in mitochon­dria starts from the NAD-linked de-hydrogen systems on the one hand through flavoproteins and cytochromes to molecular oxygen on the other. The re­ducing equivalents are transported either as H⁺ or as covalent hydrogen.

4. All substrates are not linked through NAD- specific dehydrogenases; some are linked directly to flavoprotein dehydrogenases because of their more positive redox po­tential and then linked to the cytochromes of the respiratory chain.

5. Recently, it has been established that an additional carrier is present in between flavoproteins and cytochrome b. Cyto­chrome b has the lowest redox potential among the cytochromes. This additional carrier is said to be ubiquinone or coenzyme Q (CoQ).

6. An additional component, nonheme iron (NHI), is associated with the flavoproteins and with cytochrome b.

7. At the electronegative end of the chain, dehydrogenase enzymes catalyze the transfer of electrons from the substrate to NAD of the chain.

Pyruvate and α-Ketoglutarate have complex dehydrogenase sys­tems involving lipoate and FAD before the passage of electrons to NAD. L(+)-β- hydroxyacyl – CoA, D(-)-β-hydroxybutyrate, glutamate, malate and isocitrate dehydrogenases couple directly with NAD of the respiratory chain.

8. The reduced NAD is oxidized by a metalloflavoprotein enzyme NADFI dehy­drogenase. This enzyme contains nonheme iron and the prosthetic group FMN.

9. Succinate, Glycerol-3-phosphate and acyl- CoA is linked directly to the respiratory chain through flavoprotein dehydroge­nases. The flavin moiety of these dehydrogenases in FAD and these en­zymes contain nonheme iron (NHI). In the dehydrogenation of acyl-CoA, an addi­tional flavoprotein, electron-transporting flavoprotein (ETF), is essential for trans­ferring of electrons to the respiratory chain.

10. The cytochromes are arranged in order of increasing redox potential. The terminal cytochrome a₃ (cytochrome oxidase) is re­sponsible for the final combination of re­ducing equivalents with molecular oxy­gen to form H₂O. This enzyme allows the respiratory chain to function at the maxi­mum rate until the tissue becomes virtu­ally anoxic.

Transport of Substances Into and Out of Mitochondria:

Oxidation of Extra mitochondrial NADH:

NADH is produced continuously in the cy­tosol by 3-phosphoglyceraldehyde dehydrogenase, an enzyme in the Embden-Meyerhof glycolysis but it cannot penetrate the mitochondrial membrane. Still it is oxidized by the respiratory chain in the mitochondria. This is possible by the transfer of reducing equivalents through the mitochondrial membrane via substrate pairs linked by suitable dehydrogenase.

The substrate pairs are lactate/pyru­vate, dihydroxyacetone phosphate/glycerol-3- phosphate, and malate/oxaloacetate. The specific dehydrogenase is essential to be present on both sides of the mitochondrial membrane. Lactate de­hydrogenase is found only in the cytosol and glycerol-3-phosphate dehydrogenase is NAD-linked in the cytosol, whereas the enzyme is a flavoprotein enzyme found in the mitochondria.

The mechanism of transfer is shown in the Fig. 12.25. Since the mitochondrial enzyme is linked to the respiratory chain via a flavoprotein rather than NAD, only 2 mols of ATP are formed instead of 3 mols of ATP.

Rapid oxidation of NADH occurs only when aspar­tate -a- ketoglutarate transaminase and malate de­hydrogenase together with glutamate, aspartate and malate are added to mitochondria. The complex­ity of this system is due to the impermeability of the mitochondrial membrane to oxaloacetate.

The malate “shuttle” system is also shown in (Fig. 12.25).

Energy-linked ion Transport in Mitochondria:

Actively respiring mitochondria maintain or accumulate cations such as K⁺, Na⁺, Ca⁺⁺, and Mg⁺⁺. Loss of ions from the mitochondria is due to the uncoupling with dinitrophenol. The ion uptake is not inhibited by oligomycin on the fact that the energy need not be supplied by phosphorylation of ADP.

Mitochondrial Transporter Systems:

Oxygen, water, CO₂, β-hydroxybutyrate, acetoacetate and acetate are freely permeable to the inner mitochondrial membrane. Long chain fatty acids are transported into the mitochondria by the help of carnitine system. There is a special carrier for pyruvate also.

Specific transporter or carrier sys­tems are required for the transport of amino acids, dicarboxylate and tricarboxylate anions across the membrane. Mono-carboxylate anions are more read­ily penetrated owing to the lesser degree of dissociation.

The transport of di-and tricarboxylate anions is closely linked to that of inorganic phosphate which penetrates readily as the H₂PO₄⁻ ion in ex­change for OH⁻. The uptake of malate by the dicarboxylate transporter requires inorganic phos­phate for exchange in the opposite direction.

The uptake of citrate, isocitrate or cisaconitate by the tricarboxylate transporter requires malate in ex­change. α- ketoglutarate transport also requires an exchange with malate. Thus, osmotic balance is maintained by the use of exchange mechanisms. Citrate transport across the mitochondrial mem­brane depends not only on malate transport but on the transport of inorganic phosphate also.

The ad­enine nucleotide transporter allows the exchange of ATP and ADP but not AMP. Na⁺ can be ex­changed for H⁺. Active uptake of Ca⁺⁺ by mito­chondria is facilitated by the membrane potential rather than by exchange with an ion of opposite charge. Phosphate transporter is inhibited by N- Ethyl-maleimide and Adenine nucleotide Trans­porter is inhibited by Atractyloside.