Dicarboxylic acid pathway

Alkaline pyrophosphatase dependent on Mg2+ was found in every sample examined from a broad spectrum of the plant kingdom (SI). Plants which fix C02 by the dicarboxylic acid pathway have characteristic high levels of alkaline pyrophosphatase in their chloroplasts presumably this performs the rather specific function of driving the synthesis of phosphoenolpyruvate, the immediate precursor of C02 fixation (32). Biosynthesis of the maize chloroplast enzyme is controlled by light acting through the phytochrome system (S3). Pyrophosphatase from spinach chloroplasts has been partially purified (34, 35). 

The C4 (dicarboxylic acid) pathway of photosynthetic carbon assimilation may be seen as a biochemical elaboration of the RPP cycle. In this pathway CO2 is transferred via the C-4 carboxyl of C4 acids to the reactions of the RPP cycle. Discovered in sugar cane, the pathway was first thought to be peculiar to tropical grasses but was later found in species of dicotyledons, Amaranthus (Amaranthaceae), and Atriplex (Chenopodiaceae). 

The first possibility is dubious, because there is no known biochemical oxidation reaction by which this would be accomplished. The other two possible pathways, acetone dicarboxylic acid or butyric acid, would both yield carboxyl-labeled acetoacetate, and thus 3,4-labeled glucose. The isolation of acetoacetate labeled only in the carboxyl group supports either possibility. An objection against the acetone dicarboxylic acid pathway is that acetoacetate, being a direct metabolic product of glutarate (see equation 6), should exhibit a higher specific activity than its resulting product, acetate. In the experiments of the above authors the specific... 

Hatch,M.D., Osmond,C.B. Compartmentation and transport in C4 photosynthesis. In Transport in plants III. Enzyclopedia of plant physiology. New series, Vol. 3. Stocking, C.R., Heber,U. (eds.), pp. 144-184. Berlin, Heidelberg, New York Springer 1976 Hatch, M.D., Slack, C.R. Studies on the mechanism of activation and inactivation of pyruvate, phosphate dikinase. A possible regulatory role for the enzyme in the C4 dicarboxylic acid pathway of photosynthesis. Biochem. J. 112,549-558 (1969)... 

Johnson, H.S., Hatch, M. D. Properties and regulation of leaf nicotinamide-adenine dinucleotide phosphate-malate dehydrogenase and malic enzyme in plants with the C4-dicarboxylic acid pathway of photosynthesis. Biochem. J. 779,173-280 (1970)... 

Laetsch,W.M. Chloroplast specialication on Dicotyledons possessing the C4-dicarboxylic acid pathway of photosynthetic CO2 fixation. Am. J. Bot. 55,875-883 (1968) Laetsch,W.M. The C4 syndrome a structural analysis. Ann. Rev. Plant Physiol. 25, 24-52 (1974)... 

Slack, C.R., Hatch, M.D., Goodchild,D.J. Distribution of enzymes in mesophyll and parenchyma-sheath chloroplasts of maize leaves in relation to the C -dicarboxylic acid pathway of photosynthesis. Biochem. 3.114,489-498 (1969)... 

Whelan,T., Sackett,W.M., Benedict, C.R. Enzymatic fractionating of carbon isotopes by phosphoenolpyruvate carboxylase from C4 plants. Plant Physiol. 51, 1051-1054 (1973) Whelan,T.W., Sackett,N., Benedict,C.R. Carbon isotope discrimination in a plant possessing the C4 dicarboxylic acid pathway. Biochem. Biophys. Res. Commun. 41, 1205-1210 (1970)... 

The difference between this route and the Calvin cycle lies in the fact that the CO2 is fixed, not into ribulose-l,5-diphosphate, but into phosphoenol pyruvate with the intermediary formation of C4 dicarboxylic acids. Hence the name, the Q dicarboxylic acid pathway. One of the C4 dicarboxylic acids transmits the CO2 further with the formation, ultimately, of 3-phosphoglyceric acid. 

The ecophysiological significance of the C4 dicarboxylic acid pathway is still a matter of discussion. It is striking, though, that it is also found in a large number of halophytes. This has led to the assumption that the C4 dicarboxylic acids formed via the Hatch-Slack pathway might play a role in osmoregulation in these species. However, this is only one of several possibilities. 

Various bacteria own the ability to produce propionic acid within their metabolic pathways. Present-day research is focused on strains of Propionibacteriaceae and Clostridiaceae. Propionibacteria are using the dicarboxylic acid pathway (methylmalonyl coenzyme A-pathway) to produce the desired product. These gram-positive, anaerobic bacteria are able to use glucose, sucrose, lactate, lactose and glycerol as carbon source. The metabolic end products are propionate, succinate, carbon dioxide and acetate. Professionals acknowledge Propionibacterium... 

Pterin-6-cafboxylic acid, 3,8-dimethyl-rearrangements, 3, 309 Pterincarboxylic acids occurence, 3, 323 Pterin-6-carboxylic acids acidity, 3, 277 methylation, 3, 297 synthesis, 3, 295, 304 Pterin-7-carboxylic acids acidity, 3, 277 methylation, 3, 297 synthesis, 3, 295 Pterin coenzymes biochemical pathways, 1, 260-263 Pterin-6,7-dicarboxylic acid decarboxylation, 3, 304 reactions, 3, 304... 

Another important piece of the puzzle came from the work of Carl Martius and Franz Knoop, who showed that citric acid could be converted to isocitrate and then to a-ketoglutarate. This finding was significant because it was already known that a-ketoglutarate could be enzymatically oxidized to succinate. At this juncture, the pathway from citrate to oxaloacetate seemed to be as shown in Figure 20.3. Whereas the pathway made sense, the catalytic effect of succinate and the other dicarboxylic acids from Szent-Gyorgyi s studies remained a puzzle. 

Compartmentation of these reactions to prevent photorespiration involves the interaction of two cell types, mescrphyll cells and bundle sheath cells. The meso-phyll cells take up COg at the leaf surface, where Og is abundant, and use it to carboxylate phosphoenolpyruvate to yield OAA in a reaction catalyzed by PEP carboxylase (Figure 22.30). This four-carbon dicarboxylic acid is then either reduced to malate by an NADPH-specific malate dehydrogenase or transaminated to give aspartate in the mesophyll cells. The 4-C COg carrier (malate or aspartate) then is transported to the bundle sheath cells, where it is decarboxylated to yield COg and a 3-C product. The COg is then fixed into organic carbon by the Calvin cycle localized within the bundle sheath cells, and the 3-C product is returned to the mesophyll cells, where it is reconverted to PEP in preparation to accept another COg (Figure 22.30). Plants that use the C-4 pathway are termed C4 plants, in contrast to those plants with the conventional pathway of COg uptake (C3 plants). 

As the mechanism, a radical and a cationic pathway are conceivable (Eq. 31). The stereochemical results with rac- or mcjo-1,2-diphenyl succinic acid, both yield only trans-stilbene [321], and the formation of a tricyclic lactone 51 in the decarboxylation of norbornene dicarboxylic acid 50 (Eq. 32) [309] support a cation (path b, Eq. 31) rather than a biradical as intermediate (path a). 

In suberizing potato tuber disks, labeled oleic acid was incorporated into co-hy-droxyoleic acid and the corresponding dicarboxylic acid, the two major aliphatic components of potato suberin [73]. Exogenous labeled acetate was also incorporated into all of the aliphatic components of suberin, including the very long chain acids and alcohols in the wound-healing potato slices. The time-course of incorporation of the labeled precursors into the suberin components was consistent with the time-course of suberization. The biosynthetic pathway for the major aliphatic components of suberin is shown in Fig. 8a. 

Fig. 8a, b. a Biosynthetic pathways for the major aliphatic components of suberin. b Representation of the active site of co-hydroxy acid dehydrogenase involved in the synthesis of the dicarboxylic acids characteristic of suberin. From [74]... 

In vitro synthesis of polyesters using isolated enzymes as catalyst via non-biosynthetic pathways is reviewed. In most cases, lipase was used as catalyst and various monomer combinations, typically oxyacids or their esters, dicarboxylic acids or their derivatives/glycols, and lactones, afforded the polyesters. The enzymatic polymerization often proceeded under mild reaction conditions in comparison with chemical processes. By utilizing characteristic properties of lipases, regio- and enantioselective polymerizations proceeded to give functional polymers, most of which are difficult to synthesize by conventional methodologies. 

The malate-aspartate shuttle is the most important pathway for transferring reducing equivalents from the cytosol to the mitochondria in brain. This shuttle involves both the cytosolic and mitochondrial forms of aspartate aminotransferase and malate dehydrogenase, the mitochondrial aspartate-glutamate carrier and the dicarboxylic acid carrier in brain (Fig. 31-5) [69]. The electrogenic exchange of aspartate for glutamate and a... 

Portmann and co-workers then studied the kinetic pathways in man for hydroxynalidixic acid, the active primary metabolite.(26) The rate constants for glucuronide formation, oxidation to the dicarboxylic acid and excretion of hydroxynalidixic acid were calculated. Essentially total absorption of hydroxynalidixic acid was found in every case. Good agreement between experimental and theoretical plasma levels, based on the first order rate approximations used for the model, was found. Again, the disappearance rate constant, kdoi was found to be very similar for each subject, although the individual excretion and metabolic rate constants varied widely. The disappearance rate constant, k was defined as the sum of the excretion rate constant, kg j and the metabolic rate constants to the glucuronide and dicarboxylic acid, kM-j and kgj, respectively. 

By 2D TOCSY NMR spectroscopy (TOCSY - total correlated spectroscopy), the structure of a biosynthetic intermediate of PQQ was shown to be 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid 15, not its constitutional isomer 16 <2004JA3452>. This result shows that the last enzyme on the biosynthetic pathway of PQQ facilitates a pyrrole ring closure and an unprecedented eight-electron oxidation of 15. 

Kawamura, K., and H. Kasukabe, Source and Reaction Pathways of Dicarboxylic Acids, Ketoacids, and Dicarbonyls in Arctic Aerosols One Year of Observations, Atmos. Environ., 30, 1709-1722 (1996a). 

Protons present in aqueous acid also act as reasonably efficient electron acceptors. If the reduced hydrogen atoms are formed on metallized suspensions, catalytic hydrogenation can result. For example, in contrast to the oxidative chemistry reported earlier for cyclohexene-4,5-bis-dicarboxylic acid (Eq. 28), if the reaction is conducted in the absence of oxygen in aqueous nitric acid, catalytic hydrogenation of the double bond becomes a major pathway, Eq. (34). ... 

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 ... 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

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

The first data about the bioconversion of farnesol date back to the sixties its degradation pathway is similar to that of geraniol and nerol. Seubert [139] showed that the degradation of farnesol by Pseudomonas citronellolis proceeds through the oxidation of C-l to give famesic acid, followed by carboxylation of the -methyl group. Subsequently, the 2,3-double bond of the dicarboxylic acid is hydrated to a 3-hydroxy acid which is then acted upon by a lyase resulting in the formation of a /Tketo acid and acetic acid. The /Tketo acid readily enters the fatty acid oxidation pathway [29]. 

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). 

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