Five Types of Compounds Associated With the Electron Transport System

There are five types of compounds associated with the electron transport system.

Three of these consist of enzymes whose coenzymes or prosthetic groups are known to be directly invovled in the transfer.

They are:

(1) Pyridine-linked dehydrogenases, which have either NAD⁺ or NADP⁺ as coenzymes;

(2) Flavin-linked de­hydrogenases, which are linked to flavin adenine di- nucleotides (FAD) or flavin mononucleotides (FMN);

(3) Coenzyme Q or ubiquinone, a lipid-soluble coenzyme functioning in electron transport;

(4) The cytochromes, which contain iron-porphyrin prosthetic groups; and

(5) the iron-sulfur proteins (which are chemically dis­tinct from the iron-containing cytochromes).

Pyridine-linked dehydrogenases require as their co­enzyme either NAD ⁺ or NADP ⁺ ; both NAD⁺ and NADP⁺ can accept two electrons at a time. There are about 200 dehydrogenases for which NAD⁺ or NADP⁺ serve as coenzymes. Although the NAD⁺ and NADP⁺ dehy­drogenases are found in both the cytosol and the mito­chondria and are known to transfer electrons between compounds in both places, it appears that only the NAD⁺ -linked compounds are involved in the electron transport system.

Flavin-linked dehydrogenases (often called flavopro- teins, F_P) require either FAD or FMN. Both are prosthetic groups whose isoalloxazine ring can accept two hydrogen atoms. (Prosthetic groups are firmly bound to the protein, whereas coenzymes are not.)

Flavin-linked enzymes are involved in a num­ber of enzyme systems, the more common of which are associated with fatty acid oxidation, amino acid oxidation, and Krebs cycle activity (e.g., pyruvate de­hydrogenase and succinic dehydrogenase). In general, it is not uncommon for flavin prosthetic groups and NAD⁺ coenzymes to be linked to the same protein in dehydrogenases.

Ubiquinones were so named because of their occur­rence in so many different organisms (ubiquitous means present everywhere) and their chemical resem­blance to quinone (Fig. 16-22). They are found in sev­eral different forms including the plastoquinones of chloroplasts. The form present in mitochondria is often called coeyizyme Q (CoQ or Q) and accepts two pro­tons and two electrons at a time.

The cytochromes are proteins containing iron- porphyrin (or heme) groups (Fig. 16-23). There are a large number of cytochromes in cells; most are found in mitochondria, although some function in the endo­plasmic reticulum and in chloroplasts. In mitochon­dria, five cytochromes appear to be associated with the inner membrane and are identified as cyto­chromes b, c₁, c, a, and a₃. Some occur in two or more forms, but all transfer electrons by reversible valence changes of the iron atom (Fe³⁺ <===> Fe²⁺).

In cyto­chromes b, c₁, c, and a, the manner of binding of iron in the porphyrin ring and its association with the pro­tein prevent the iron ligands from forming with oxy­gen, and therefore these reduced cytochromes cannot be directly oxidized by molecular oxygen.

Cytochrome a₃, which is the terminal carrier in the electron trans­port system and which together with cytochrome a forms the cytochrome oxidase complex, is an excep­tion and can be directly oxidized by oxygen. In addi­tion to cytochromes a and a₃, cytochrome oxidase con­tains copper. Electrons received from cytochrome c are picked up by cytochrome a and then transferred from a₃ to oxygen by Cu²⁺<===> Cu⁺ intermediation.

Iron-sulfur proteins of mitochondria are electron carriers containing iron and sulfur in equal amounts. The iron is reversibly oxidized during the electron transfer. Certain iron-sulfur groups occur in associa­tion with flavoproteins and others are associated with the NADH dehydrogenase complex and the cyto­chrome b and c complex. The term iron-sulfur center is used to denote any Fe-S association. Iron-sulfur proteins transfer one electron at a time.

Electron Transport Pathway:

It has taken about 50 years to work out the chain of mitochondrial electron transfer shown in Figure 16- 24. During the early 1900s, several investigators (no­tably T. Thunberg) discovered a number of dehydro­genase enzymes. In 1913, O. Warburg discovered that cyanide inhibits oxygen consumption but does not in­terfere with dehydrogenases. He proposed the exis­tence of iron-containing “respiratory enzymes,” now recognized as the cytochromes.

The flavoproteins were identified by A. Szent-Gyorgyi as the intermedi­ates between dehydrogenases and the respiratory en­zymes. F. L. Crane discovered ubiquinone and a num­ber of other investigators, notably Keilin, Kuhn, Green, Chance, Racker, and Lehninger, added details about the chemistry of the intermediates in electron transfer and the sequence of the reactions. Among the Nobel Prize recipients who contributed to our early understanding of electron transport are Warburg, Szent-Gyorgyi, and Kuhn.

Today we visualize the electron transport chain as an orderly sequence of compounds through which the hydrogens and electrons are passed. The fact that the electrons do not jump or “short-circuit” to stronger oxidizing agents is probably related to the specific physical positioning of the coenzymes in the inner membrane. However, hydrogen or electrons may en­ter the chain at various points.

Most electrons are removed from the substrates in the cytosol or the matrix of the mitochondria by NAD ⁺ – (or NADP⁺-) linked dehydrogenases. The NADH produced in the matrix conveys the electrons to the NAD ⁺-flavoprotein-linked dehydrogenase in the inner membrane of the mitochondrion.

As shown in Figure 16-24, the NADH is then oxidized by F_P, which now being reduced is in turn reoxidized by ubi­quinone (Q). Reduced Q is subsequently reoxidized by cytochrome b and the reduced iron in cytochrome 6 is then reoxidized by cytochrome c₁.

Finally, cytochrome oxidase accepts the electrons from cytochrome c, pass­ing them from cytochrome a to a₃ and subsequently to oxygen. The acceptance of the electrons by oxygen oc­curs at the same time as the incorporation of 2 H⁺, thereby forming water.

During one complete transfer, each of the coenzymes in the chain is reoxidized and is available to be reduced again. Pyruvate dehydro­genase, malate dehydrogenase, isocitrate dehydro­genase, and α-ketoglutarate dehydrogenase are exam­ples of enzymes initiating the electron transfer chain through NAD⁺.

Succinate dehydrogenase oxidizes succinate, and the electrons removed are bound to FAD. The FAD_SUC is reoxidized by giving up its elec­trons to ubiquinone (Q), thereby bypassing the NAD⁺ step. Fatty acyl-CoA and glycerol phosphate are oxi­dized in a similar manner with entry of electrons di­rectly from their flavoproteins to Q.