Oxidative decarboxylation reactions

Thiamin has a central role in energy-yielding metabo-hsm, and especially the metabohsm of carbohydrate (Figure 45-9). Thiamin diphosphate is the coenzyme for three multi-enzyme complexes that catalyze oxidative decarboxylation reactions pymvate dehydrogenase in carbohydrate metabolism a-ketoglutarate dehydro-... 

The oxidative decarboxylation reaction above is part of the TCA cycle and leads to the formation of oxaloacetate, which maybe used to synthesize citrate (with acetyl-CoA) or may be used as a substrate by phosphoenol pyruvate carboxykinase, PEPCK. It should be noted that the phosphoenolpyruvate generated by PEPCK reaction shown above is... 

Notably, nitrile-degrading enzymes (e.g. nitrilase that converts the CN group to carboxylic acid, and nitrile hydratase that produces an amide function) have been described, and they co-exist with aldoxime-degrading enzymes in bacteria (Reference 111 and references cited therein). Smdies in this area led to the proposal that the aldoxime-nitrile pathway, which is implemented in synthesis of drugs and fine chemicals, occurs as a natural enzymic pathway. It is of interest that the enzyme responsible for bacterial conversion of Af-hydroxy-L-phenylalanine to phenacetylaldoxime, an oxidative decarboxylation reaction, lacks heme or flavin groups which are found in plant or human enzymes that catalyze the same reaction. Its dependency on pyridoxal phosphate raised the possibility that similar systems may also be present in plants . 

FIGURE 16-13 Products of one turn of the citric acid cycle. At each turn of the cycle, three NADH, one FADH2/ one GTP (or ATP), and two C02 are released in oxidative decarboxylation reactions. Here and in several following figures, all cycle reactions are shown as proceeding in one direction only, but keep in mind that most of the reactions are reversible (see Fig. 16-7). 

The second of two oxidative decarboxylation reactions of the TCA cycle is catalyzed by a-ketoglutarate dehydrogenase. The reaction sequence is analogous to that of pyruvate dehydrogenase, complete with the conversion of some of the energy of the oxidation in a coenzyme-containing derivative, succinyl-CoA. 

The reactions catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase are both oxidative decarboxylation reactions. How similar are the reactions ... 

Thus phenol formation from the monocarboxylic acids described above supports the suggestion that the 1,2-oxides of aromatic carboxylic acids may be the intermediates in their biological oxidative decarboxylation reactions. 

Recent model studies strongly support the proposed mechanism. The first crystal structures of Fe(II) complexed to benzoylformate show that an a-keto acid can coordinate to the iron as either a monodentate or didentate ligand [236]. Exposure of these [Fe(II)(L)(bf)]+ complexes (L = tmpa or 6-Me3-tmpa) to 02 results in the quantitative conversion of benzoylformate to benzoic acid and C02, modeling the oxidative decarboxylation reaction characteristic of this class of enzymes. As with the enzymes, the use of 1802 in the model studies results in the incorporation of the label into the benzoate product. For [Fe(6-Me3-tmpa)(bf)]+, the rate of the oxidative decarboxylation increases as the substituent of the benzoylformate becomes more electron-withdrawing, affording a Hammett p of +1.07. This suggests that the oxidative decarboxylation involves a nucleophilic attack, most plausibly by the iron-bound 02, on the keto carbon of benzoylformate to initiate decarboxylation as proposed in Figure 27. 

In this process, cumene is oxidized to cumene hydroperoxide by air at about 100°C in an alkaline environment. The oxidation products are separated, and the bottoms are mixed with a small amount of acetone and sulfuric acid and held at 70-80°C while the hydroperoxide splits into phenol and acetone. Total domestic phenol capacity with this process is about 4.8 billion lb/year. In the much smaller-volume benzoic acid process, toluene is air-oxidized to benzoic acid with a cobalt catalyst. The benzoic acid then is converted to phenol by an oxidative decarboxylation reaction with air at about 240°C. 

In 1970, Anderson and Kochi (99) reported a silver-mediated oxidative decarboxylation reaction with peroxydisulfate as the oxidant. Kinetic studies showed that the reaction is first order in both silver and peroxydisulfate and zero order in carboxylic acid. Silver(II) species and alkyl radicals are considered intermediates. 

The conversion of isocitrate into a-ketoglutarate is followed by a second oxidative decarboxylation reaction, the formation of succinyl CoA from a-ketoglutarate. 

Isocitrate is oxidized to a-ketoglutarate in the first oxidative decarboxylation reaction. COz is produced, and the electrons are passed to NAD+ to form NADH + H+. 

The product of this oxidative decarboxylation reaction is a-ketoglutarate ... 

CoA thioesters are also the products of the oxidative decarboxylation reactions of a-keto acids, especially pyruvate and a-ketoglutarate, from which acetyl-CoA and succinyl-CoA are formed, respectively (Equation (14)). Three distinct types of enzymes catalyze such reactions however, the mechanistic involvement of CoA is generally rather limited for two of these, and only a brief discussion of each will be provided here. For more detailed information on these enzymes, the reader is referred to the relevant chapters on thiamin and lipoic acid enzymology and on radical enzymes in this series (see Chapters 1.08 and 7.03). 

CO2 concentration for the oxidative decarboxylation reactions are also much larger than those for simple dehydrogenations 163). These facts can be related to the different redox states of NAD and NADP in the cytoplasm, and to the different metabolic roles of NADH and NADPH (135,163)—and teleologically to the reason for the specificity of the cytoplasmic oxidative decarboxylases for NADP, perhaps. 

Fig. 29.6. Oxidative portion of the pentose phosphate pathway. Carbon 1 of glucose 6-phosphate is oxidized to an acid and then released as CO2 in an oxidative decarboxylation reaction. Each oxidation step generates an NADPH.

The most thoroughly studied peptide complexes are those of Cu" and Ni even so they are capable of giving unexpected results, e.g. the aforementioned Cu"-catalyzed hydrolysis of hexagly-cine." Attempts to prepare a crystalline complex by reacting Gly-Gly-L-His with Cu(OH)2 resulted in crystals of the decarboxylated product (25)." A similar reaction has been observed with Ni . These are examples of oxidative decarboxylation reactions. Just as unexpectedly Margeram and his co-workers found that neutral aqueous solutions of Ni" or Cu" tetra- and penta-peptide complexes absorbed Oj to give a number of products. Resulting from these observations has come... 

If it arises from pyruvate (Topic 14), the formation of acetyl CoA is pushed by the energetically favourable oxidative decarboxylation reaction. If, on the other hand, one starts from acetate, or similarly from a long-chain fatty acid waiting to enter the fatty oxidation spiral, the formation of the acyl CoA involves an activation reaction in which ATP is split. 

Oxidative decarboxylation. Reaction of a-keto acids, for example, -keto-valcric acid (I), with singlet oxygen leads to evolution of CO2 and formation of the corresponding carboxylic acid (2). The same reaction can be carried out, but... 

The mechanism of this oxidative decarboxylation reaction is different from the oxidative decarboxylation of pyruvate. In particular there is no involvement of thiamine pyrophosphate or... 

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