Proton transfer, chain reactions

If we consider the fate of substrate AH2 during the action of a peroxidase, we see that donation of an electron to compound I to convert it into II (Fig. 16-14, step c) will generate a free radical AH as well as a proton. The radical may then donate a second electron to II to form the free enzyme. Alternatively, a second molecule of AH2 may react (Fig. 16-14, step c) to form a second radical AH. The two AH radicals may then disproportionate to form A and AH2 or they may leave the enzyme and react with other molecules in their environment. Compound II of horse radish peroxidase is able to exchange the oxygen atom of its Fe(IV)=0 center with water rapidly at pH 7, presumably by donation of a proton from the nearby histidine side chain (corresponding to His 52 of Fig. 16-13).227/230a/b This histidine presumably also functions in proton transfer during reactions with substrates (see Fig. 16-11B).224... 

Drukker, K., Hammes-Schiffer, S. An analytical derivation of MC-SCF vibrational wave functions for the quantum dynamical simulation of multiple proton transfer reactions Initial application to protonated water chains. J. Chem. Phys. 107 (1997) 363-374. 

H atom is attached to an N atom at the end of the chain), (hi If HN, is added to NH, a proton transfer reaction occurs. Wo the chemical equation for that reaction. 

The occurrence of proton transfer reactions between Z)3+ ions and CHa, C2H, and NDZ, between methanium ions and NH, C2HG, CzD , and partially deuterated methanes, and between ammonium ions and ND has been demonstrated in irradiated mixtures of D2 and various reactants near 1 atm. pressure. The methanium ion-methane sequence proceeds without thermal activation between —78° and 25°C. The rate constants for the methanium ion-methane and ammonium ion-ammonia proton transfer reactions are 3.3 X 10 11 cc./molecule-sec. and 1.8 X 70 10 cc./molecule-sec., respectively, assuming equal neutralization rate constants for methanium and ammonium ions (7.6 X 10 4 cc./molecule-sec.). The methanium ion-methane and ammonium ion-ammonia sequences exhibit chain character. Ethanium ions do not undergo proton transfer with ethane. Propanium ions appear to dissociate even at total pressures near 1 atm. 

The mechanism for the lipase-catalyzed reaction of an acid derivative with a nucleophile (alcohol, amine, or thiol) is known as a serine hydrolase mechanism (Scheme 7.2). The active site of the enzyme is constituted by a catalytic triad (serine, aspartic, and histidine residues). The serine residue accepts the acyl group of the ester, leading to an acyl-enzyme activated intermediate. This acyl-enzyme intermediate reacts with the nucleophile, an amine or ammonia in this case, to yield the final amide product and leading to the free biocatalyst, which can enter again into the catalytic cycle. A histidine residue, activated by an aspartate side chain, is responsible for the proton transference necessary for the catalysis. Another important factor is that the oxyanion hole, formed by different residues, is able to stabilize the negatively charged oxygen present in both the transition state and the tetrahedral intermediate. 

P. Mitchell (Nobel Prize for Chemistry, 1978) explained these facts by his chemiosmotic theory. This theory is based on the ordering of successive oxidation processes into reaction sequences called loops. Each loop consists of two basic processes, one of which is oriented in the direction away from the matrix surface of the internal membrane into the intracristal space and connected with the transfer of electrons together with protons. The second process is oriented in the opposite direction and is connected with the transfer of electrons alone. Figure 6.27 depicts the first Mitchell loop, whose first step involves reduction of NAD+ (the oxidized form of nicotinamide adenosine dinucleotide) by the carbonaceous substrate, SH2. In this process, two electrons and two protons are transferred from the matrix space. The protons are accumulated in the intracristal space, while electrons are transferred in the opposite direction by the reduction of the oxidized form of the Fe-S protein. This reduces a further component of the electron transport chain on the matrix side of the membrane and the process is repeated. The final process is the reduction of molecular oxygen with the reduced form of cytochrome oxidase. It would appear that this reaction sequence includes not only loops but also a proton pump, i.e. an enzymatic system that can employ the energy of the redox step in the electron transfer chain for translocation of protons from the matrix space into the intracristal space. 

In biochemical systems, acid-base and redox reactions are essential. Electron transfer plays an obvious, crucial role in photosynthesis, and redox reactions are central to the response to oxidative stress, and to the innate immune system and inflammatory response. Acid-base and proton transfer reactions are a part of most enzyme mechanisms, and are also closely linked to protein folding and stability. Proton and electron transfer are often coupled, as in almost all the steps of the mitochondrial respiratory chain. 

We next focus on the use of fixed-site cofactors and coenzymes. We note that much of this coenzyme chemistry is now linked to very local two-electron chemistry (H, CH3", CH3CO-, -NH2,0 transfer) in enzymes. Additionally, one-electron changes of coenzymes, quinones, flavins and metal ions especially in membranes are used very much in very fast intermediates of twice the one-electron switches over considerable electron transfer distances. At certain points, the chains of catalysis revert to a two-electron reaction (see Figure 5.2), and the whole complex linkage of diffusion and carriers is part of energy transduction (see also proton transfer and Williams in Further Reading). There is a variety of additional coenzymes which are fixed and which we believe came later in evolution, and there are the very important metal ion cofactors which are separately considered below. 

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