The Dicarboxylic Acid Cycle

Figure 17-6 The dicarboxylic acid cycle for oxidation of glyoxylate to carbon dioxide. The pathway for synthesis of the regenerating substrate Carbohydrate synthesis...

Metabolic cycle a catalytic series of reactions in which the product of one bimolecular reaction is regenerated A-tB->->—>C + A. Thus A acts catalyti-cally, is required only in small amounts, and can be considered as a carrier of B.The catalytic function of A and other members of the M.c. insure economic conversion of B into C. B is the substrate of the M.c. and C is the product. If intermediates are withdrawn from the M.c., e.g. for biosynthesis, the stationary concentrations of the M.c. intermediates must be maintained by synthesis. Replenishment of depleted M.c. intermediates is called anaplerosis. Only one anaplerotic reaction is necessary, since the resulting intermediate is in equilibrium with all other members of the cycle. Anaplerosis may be served by a single reaction, which converts a common metabolite into an intermediate of the M.c. (e.g. pyruvate to oxalo-acetate in the tricarboxylic acid cycle), or it may involve a metabolic sequence of reactions, i. e. an anaplerotic sequence (e.g. the glycerate pathway which provides phosphoenofpyruvate for anaplerosis of the dicarboxylic acid cycle). 

Dicarboxylic acid cycle discovered by Szent-Gyorgi. Krebs and Johnson. The tricarboxylic (citric) acid cycle. 

Some bacteria use a "dicarboxylic acid cycle" to oxidize glyoxylate OHC-COO to C02. The regenerating substrate for this cycle is acetyl-CoA. It is synthesized from glyoxylate by a complex pathway that begins with conversion of two molecules of glyoxylate to tartronic semialdehyde ... 

Catabolism of amino acids usually entails their conversion to intermediates in the central metabolic pathways. All amino acids can be degraded to carbon dioxide and water by appropriate enzyme systems. In every case, the pathways involve the formation, directly or indirectly, of a dicarboxylic acid intermediate of the tricarboxylic acid cycle, of pyruvate, or of acetyl-CoA (fig. 22.11). 

The carboxylic acids can be subdivided into nonvolatile fatty acids, volatile fatty acids, hydroxy acids, dicarboxylic acids, and aromatic acids (Fig. 3). The nonvolatile fatty acids are molecules with more than five carbon atoms, such as stearic and palmitic acids, which are the degradation products of fats and triglycerides. Three different 18-C fatty acids that are important constituents of plants include oleic and linoleic acids that are abundant in plant seeds, and linolenic acid, which is abundant in plant leaves. Volatile fatty acids are short-chain molecules with one to five carbon atoms, such as acetic and valeric acid, associated with anaerobic metabolism. The hydroxy-acids are common intermediates in biochemical pathways, including the tricarboxylic acid cycle. The excretion of hydroxyacids by algae, such as the... 

Succinic acid is a dicarboxylic acid produced as an intermediate of the tricarboxylic acid cycle and also as one of the fermentation products of anaerobic metabolism. It has been considered an important chemical because it can be used for the precursor of 1,4-butanediol, tetrahydrofu-ran, and y-butyrolactone as well as for application in polymers, foods, pharmaceuticals, and cosmetics (1,2). Currently, succinic acid is produced commercially through chemical synthesis. However, the production of... 

The citric acid cycle is the central metabolic hub of the cell. It is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid. The cycle is also an important source of precursors, not only for the storage forms of fuels, but also for the building blocks of many other molecules such as amino acids, nucleotide bases, cholesterol, and porphyrin (the organic component of heme). 

It was hypothesized that succinic acid, the principal fermentative dicarboxyl acid in wine, is formed in the tricarboxyl acids cycle (Figure 1.4). Even if this metabolism is not used by microorganisms in fermentation, the enzymes involved are able to operate liberation of succinic acid. 

Fig. 3. Dicarboxylic acids not members of the tricarboxylic acid cycle found in normal urine.

The S5mthetic pathway for the regenerating substrate of e dicarboxylic acid cycle is quite complex. Two molecules of glyoxylate imdergo a condensation with decarboxylation by glyoxylate carboligase ... 

Succinic acid, known as amber acid or butanedioic acid, is a four-carbon dicarboxylic acid produced as an intermediate of the tricarboxylic acid cycle (TCA) [1,2]. Succinic acid and its derivative have wide industrial applications such as the feedstock of food and pharmaceutical products, as the intermediate of chemical synthesis of surfactants, detergents, green solvents, and biodegradable plastics, and also as ingredients of animal feeds to stimulate animal and... 

In 1935, Albert Szent-Gyorgyi demonstrated the steps that connected the four four-carbon dicarboxylic acids succinate, fumarate, malate, and oxaloacetate, and he discovered that these compounds are catalytic (not consumed). However, in 1937 it was Krebs who made the critical finding that citric acid is also catalytic, added four more compounds (Cg and C5 species), and finally closed the loop on the citric acid cycle. 

Malic acid monohydroxysuccinic acid, HOOC-CHOH-CHj- OOH, a dicarboxylic acid found in many plant juices, usually in the L(-i-)-form, m.p. 100°C, b.p. 140°C (d.). The malate ion is formed in the Thcarboxylic acid cycle (see) and in the Glyoxy-late cycle (see). Malate plays an important role in the Diurnal acid rhythm (see) of the Crassulaceae (stonecrop family). 

Malonic add HOOC-CH2-COOH, a dicarboxyl-ic acid, m.p. 135.6 °C, which has been found in the free form in plants, but is of only sporadic occurrence. At the pH of the cell M.a. is present as its anion (mal-onate), which is a known competitive inhibitor of succinate dehydrogenase in the tricarboxylic acid cycle. A metabolically important derivative of M.a. is malo-nyl-CoA, an intermediate of Fatty acid biosynthesis (see). 

A further development of the Mopac process led to the KWU Cord process (Chemical—Oxidation—Reduction-Decontamination), a multi-cycle, low-concentration process which proved to be especially suitable for the decontamination of subsystems and full reactor systems (Wille and Sato, 1994). The principles of this process are shown in Fig. 4.52. A CoRD decontamination cycle starts with an oxidation step, using a dilute solution of permanganic acid the excess Mn04 is then reduced by addition of a dicarboxylic acid, thereby generating CO2. By further addition of the dicarboxylic acid up to a concentration of about 0.2%, dissolution of the oxides starts and the metal ions are retained in the solution as complex compounds. The whole process is conducted at about 95 C it does not require a fixed number of cycles, but can be repeated according to the final radiation dose... 

In the period between 1935 and 1950 there was discovered a principal way in which the oxidation of carbohydrates to water and carbon dioxide is carried out with production of a number of high-energy molecules for each molecule of carbon dioxide formed. This biochemical mechanism is called the citric acid cycle or the Krehs cycle. It was in large part formu- lated by 1943 by the British biochemist Hans Adolf Krebs (born 1900), after Albert Szent-Gyorgyi in 1935 had discovered that enzymes from muscle could catalyze the oxidation of dicarboxylic four-carbon acids (succinic, fumaric, malic, and oxaloacetic acid). 

---