Citric acid transformation

Brandange S, Dahlman O (1983) Synthesis of stereoselectively labelled citric acid transformable into chiral acetic acids. J Chem Soc Chem Commun 1324-1325... 

In some cases enzymes can increase the rate of reaction by up to lO times. Carnell and Roberts (1997) have briefly discussed the scope of biotransformations that are used to make pharmaceuticals like penicillins, cephalosporines, erythromycin, lovastatin, cyclosporin, etc., and for food additives like citric acid, L-glutamate, and L-lysine. A very successful transformation by Zeneca has been that of benzene reduction, with Pseudomonase Putida, to dihydrocatechol and catechol the dihydro derivative is used to produce (+/-) pinitol. Fluorobenzene has been converted to fluorodihydrocatechol, an intermediate for pharmaceuticals. The highly stereo selective Bayer-Villeger reaction has been carried out with genetically engineered S-cerevisvae. Hydrolases have allowed enantioselective, and in some cases regioselective, hydrolysis of racemic esters. 

The osmium-catalyzed dihydroxylation reaction, that is, the addition of osmium tetr-oxide to alkenes producing a vicinal diol, is one of the most selective and reliable of organic transformations. Work by Sharpless, Fokin, and coworkers has revealed that electron-deficient alkenes can be converted to the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side [199]. One of the most useful additives in this context has proved to be citric acid (2 equivalents), which, in combination with 4-methylmorpholine N-oxide (NMO) as a reoxidant for osmium(VI) and potassium osmate [K20s02(0H)4] (0.2 mol%) as a stable, non-volatile substitute for osmium tetroxide, allows the conversion of many olefinic substrates to their corresponding diols at ambient temperatures. In specific cases, such as with extremely electron-deficient alkenes (Scheme 6.96), the reaction has to be carried out under microwave irradiation at 120 °C, to produce in the illustrated case an 81% isolated yield of the pure diol [199]. 

Examples of solvent-mediated transformation monitoring include the conversion of anhydrous citric acid to the monohydrate form in water [235,236], CBZ with water [237] and ethanol-water mixtures [238,239], and cocrystallization studies of CBZ, caffeine, and theophylline with water [240]. Raman spectroscopy was used to monitor the crystallization rate and solute and solvent concentrations as griseofulvin was removed from an acetone solution using supercritical CO2 as an antisolvent [241]. Progesterone s crystallization profile was monitored as antisolvent was added [242]. 

Vinblastine suppresses cell growth during metaphase, affects amino acid metabolism, in particular at the level of including glutamine acid into the citric acid cycle and preventing it from transformation into urea, and it also inhibits protein and nucleic acid synthesis. 

The toxicity of fluoroacetic acid and of its derivatives has played an historical decisive role at the conceptual level. Indeed, it demonstrates that a fluorinated analogue of a natural substrate could have an activity profile that is far different from that of the nonfluorinated parent compound. The toxicity of fluoroacetic acid is due to its ability to block the citric acid cycle (Krebs cycle), which is an essential process of the respiratory chain. The fluoroacetate is transformed in vivo into 2-fluorocitrate by the citrate synthase. It is generally admitted that aconitase (the enzyme that performs the following step of the Krebs cycle) is inhibited by 2-fluorocitrate the formation of aconitate through elimination of the water molecule is a priori impossible from this substrate analogue (Figure 7.1). 

In examining the eight successive reaction steps of the citric acid cycle, we place special emphasis on the chemical transformations taking place as citrate formed from acetyl-CoA and oxaloacetate is oxidized to yield C02 and the energy of this oxidation is conserved in the reduced coenzymes NADH and FADH2. 

On the other hand, the intermediate fraction (G3) shows an increase in TOC. This shift could be partially due to transformation of the HMW to fraction G3. However, the increase in TOC for fraction G3 seems to be too great to be explained solely by migration from Gl to G3. Thus, some of the TOC may have shifted from G5 to G3, either because of the formation of polar oxidation byproducts with elution volumes matching those of G3 (under the experimental conditions used, certain carboxylic acids such as acetic or citric acid would be eluted in fraction G3) or possibly by the mechanism of oxidative polymerization (15,16). 

The transformation of pyruvate to carbon dioxide is achieved by the several steps in a cyclical series of reactions known as the tricarboxylic acid (TCA) cycle. The name of the cycle comes from the first step where acetyl-CoA is condensed with oxaloacetic acid to form citric acid, a tricarboxylic acid. Once citrate is formed the material is converted back to oxaloacetate through a series of 10 reactions, as illustrated in Fig. 5.22, with the net production of 2 molecules of carbon dioxide and reducing equivalents in the form of 4 molecules of NADH + H and 1 molecule of FADH2, together with 1 mole of ATP. The overall stoichiometry of the TCA cycle from pyruvate is ... 

The dicarboxylate/4-hydroxybutyrate cycle starts from acetyl-CoA, which is reductively carboxylated to pyruvate. Pyruvate is converted to PEP and then car-boxylated to oxaloacetate. The latter is reduced to succinyl-CoA by the reactions of an incomplete reductive citric acid cycle. Succinyl-CoA is reduced to 4-hydroxybu-tyrate, the subsequent conversion of which into two acetyl-CoA molecules proceeds in the same way as in the 3-hydroxypropionate/4-hydroxybutyrate cycle. The cycle can be divided into part 1 transforming acetyl-CoA, one C02 and one bicarbonate to succinyl-CoA via pyruvate, PEP, and oxaloacetate, and part 2 converting succinyl-CoA via 4-hydroxybutyrate into two molecules of acetyl-CoA. This cycle was shown to function in Igrticoccus hospitalis, an anaerobic autotrophic hyperther-mophilic Archaeum (Desulfurococcales) [40]. Moreover, this pathway functions in Thermoproteus neutrophilus (Thermoproteales), where the reductive citric acid cycle was earlier assumed to operate, but was later disproved (W.H. Ramos-Vera et al., unpublished results). 

Table 4.10 Standard Transformed Reaction Gibbs Energies for Pyruvate Dehydrogenase, the Citric Acid Cycle, and Net Reactions at 298.15 K and 0.25 M Ionic Strength...

Acetyl-CoA is oxidized to carbon dioxide via the citric acid cycle (Chap. 12), thus transforming additional energy to that which has been transformed via /3-oxidation. In liver mitochondria only, acetyl-CoA may also be converted to ketone bodies ... 

Many other reactions use NADH as a reducing agent or NAD+ as oxidizing agent. Three molecules of NAD+ are used in the citric acid cycle (see the chart on p. 1393). One of these oxidations is the simple transformation of a secondary alcohol (malate) to a ketone (oxaloacetate). 

Of all the metabolic activities that lactic acid bacteria can carry out in wine, the most important, or desirable, in winemaking is the breakdown of malic acid, but only when it is intended for this to be removed completely from the wine by malolactic fermentation. Although the breakdown of malic and citric acids has considerable consequences from a winemaking perspective, it is also evident that lactic acid bacteria metabolise other wine substrates to ensure their multiplication, including sugars, tartaric acid, glycerine and also some amino acids. We will now describe some of the metabolic transformations that have received most attention in the literature, or which have important repercussions in winemaking. 

Citric acid is transformed into oxaloacetate and acetate in a reaction catalysed by citrate-lyase (CL). 

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). 

What is the function of the citric acid cycle in transforming fuel molecules into ATP Recall that fuel molecules are carbon compounds that are capable of being oxidized—of losing electrons (Chapter 14). The citric acid cycle includes a series of oxidation-reduction reactions that result in the oxidation of an acetyl group to two molecules of carbon dioxide. 

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