Coenzymes mobile

Metabolism and Mobilization. On entry of vitamin B 2 into the cell, considerable metaboHsm of the vitamin takes place. Co(III)cobalamin is reduced to Co(I)cobalamin, which is either methylated to form methylcobalamin or converted to adenosylcobalamin (coenzyme B>22)- The methylation requires methyl tetrahydrofolate. 

The final step of the reaction involves the transfer of two electrons from iron-sulfur clusters to coenzyme Q. Coenzyme Q is a mobile electron carrier. Its isoprenoid tail makes it highly hydrophobic, and it diffuses freely in the hydrophobic core of the inner mitochondrial membrane. As a result, it shuttles electrons from Complexes I and II to Complex III. The redox cycle of UQ is shown in Figure 21.5, and the overall scheme is shown schematically in Figure 21.6. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

It is here that we hit a central feature of every organism as well as the most primitive. There has to be spatial structure, there has to be flow, and there has to be communication to co-ordinate the activities of the cell. The communication has to link the metabolic paths and consists in the primitive cell of feedback controls by small molecules (mobile coenzymes and substrates) and ions, where up to 20 elements are involved. By seeing... 

In modern anaerobic prokaryotes and in fact in all the prokaryotes we know about, the metabolic paths have changed little from those described above but details have. The essential feature is the flow of C, H, N, O, P and S compounds into and out of cells in an incomplete cycle. The first big evolutionary advance must have been made by introducing coenzymes - both freely mobile, where mobile includes swinging attached arms, and at fixed sites, to aid flow. The known coenzymes are so-called because they all also assist catalysis. This cannot be an... 

Only metal ions Mo (W), in a certain organic complex later and which can be considered to be a semi-mobile coenzyme (see Section 5.9) are known to catalyse... 

There are a series of non-mobile coenzymes based on the so-called isoalloxine rings, which include flavins and pteridines. Their early function was the transfer of hydrogen inside membranes or in complicated enzymes, so we have... 

Mobile coenzymes Distribution of metabolic fragments H , CH3, -COCH3, etc. 

The role of ubiquinone (coenzyme Q, 4) in transferring reducing equivalents in the respiratory chain is discussed on p. 140. During reduction, the quinone is converted into the hydroquinone (ubiquinol). The isoprenoid side chain of ubiquinone can have various lengths. It holds the molecule in the membrane, where it is freely mobile. Similar coenzymes are also found in photosynthesis (plastoquinone see p. 132). Vitamins E and K (see p. 52) also belong to the quinone/hydroquinone systems. 

An important aspect of PDH catalysis is the spatial relationship between the components of the complex. The covalently bound lipoamide coenzyme is part of a mobile domain of E2, and is therefore highly mobile. This structure is known as the lipoamide arm, and swings back and forth between El and E3 during catalysis. In this way, lipoamide can interact with the TPP bound at El, with solute coenzyme A, and also with the FAD that serves as the electron acceptor in E3. 

In addition to NAD and flavoproteins, three other types of electron-carrying molecules function in the respiratory chain a hydrophobic quinone (ubiquinone) and two different types of iron-containing proteins (cytochromes and iron-sulfur proteins). Ubiquinone (also called coenzyme Q, or simply Q) is a lipid-soluble ben-zoquinone with a long isoprenoid side chain (Fig. 19-2). The closely related compounds plastoquinone (of plant chloroplasts) and menaquinone (of bacteria) play roles analogous to that of ubiquinone, carrying electrons in membrane-associated electron-transfer chains. Ubiquinone can accept one electron to become the semi-quinone radical ( QH) or two electrons to form ubiquinol (QH2) (Fig. 19-2) and, like flavoprotein carriers, it can act at the junction between a two-electron donor and a one-electron acceptor. Because ubiquinone is both small and hydrophobic, it is freely diffusible within the lipid bilayer of the inner mitochondrial membrane and can shuttle reducing equivalents between other, less mobile electron carriers in the membrane. And because it carries both electrons and protons, it plays a central role in coupling electron flow to proton movement. 

The inner mitochondrial membrane can be disrupted into five sepa rate enzyme complexes, called complexes I, II, III, IV, and V. Complexes I to IV each contain part of the electron transport chain (Figure 6.8), whereas complex V catalyzes ATP synthesis (see p. 78). Each complex accepts or donates electrons to relatively mobile electron carriers, such as coenzyme Q and cytochrome c. Each car rier in the electron transport chain can receive electrons from an electron donor, and can subsequently donate electrons to the next carrier in the chain. The electrons ultimately combine with oxygen and protons to form water. This requirement for oxygen makes the electron transport process the respiratory chain, which accounts for the greatest portion of the body s use of oxygen. 

Coenzyme Q (ubiquinone) is an essential cofactor in the electron transport chain in which it accepts electrons from complex I and II. Coenzyme Q also serves as an important antioxidant in both mitochondria I and lipid membranes. Coenzyme Q is a lipid-soluble compound composed of a redox active quinoid moiety and a hydrophobic tail. The predominant form of coenzyme Q in humans is coenzyme Q10, which contains ten isoprenoid units in the tail, whereas the predominant form in rodents is coenzyme Q9, which has nine isoprenoid units in the tail. Coenzyme Q is soluble and mobile in the hydrophobic core of the phospholipid bilayer of the inner membrane of the mitochondria in which it transfers electrons one at a time to complex III of the electron transport chain. 

This has been one of the most controversial areas of bioenergetics and is concerned with the role of coenzyme Q. The simplest view of the role of this coenzyme is that it acts as a mobile (2H+ + 2e ) carrier, linking complexes I and II with complex III. However, coenzyme Q may be involved in (H+ + e ) transfer within complex III. One model for this is the proton-motive Q cycle (Fig. 14-6), developed by Mitchell in 1975. This model satisfies prediction (2) of Example 14.10, in that coenzyme Q acts as an (H+ +e ) carrier in two loops. In this model, reduced coenzyme Q (QH2) is linked to oxidized coenzyme Q (Q) via the free-radical semiquinone (QH-) This model provides an explanation for the H+/e stoichiometry. 

Excess acetate (C2) can be converted to the mobile ketone body energy source aceto-acetate (C4) and thence its reduced form hydroxybutyrate (C,) for transport throughout the body. Excess acetate can be carboxylated (via acetylCoA carboxylase) to form malonylCoA (C3), the donor for further C2 additions (with C02 elimination) in the anabolic synthesis of long chain fatty acids. Fatty acids are components of the phospholipids of cellular membranes and are also stored as triacylglycerols (triglycerides) for subsequent hydrolysis and catabolic fatty acid oxidation to yield reduced coenzymes and thence ATP (see Chapter 2). 

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