Tricarboxylate anions

Cytosolic generation of acetyl-CoA ( citrate shuttle ) This pathway is shown in Figure 18-13. Citrate synthesized from oxaloacetate and acetyl-CoA is transported to the cytosol via the tricarboxylate anion carrier system and cleaved to yield acetyl-CoA and oxaloacetate. 

S), have been prepared. The first set of compounds binds anions in the order Cl > Br > CN, has only a small affinity for 1 and SCN, and has no affinity for F and H2P04. . The second set of compounds, possessing C3 symmetry and containing three urea or thiourea groups, shows selectivity for Br over Cl and a high affinity for tricarboxylate anions such as benzene-1,3,5-tricarboxylate — 87,000 when X = O 190,000 M" when X = S),... 

Fig. 8. Pathways involved in the conversion of glucose to fatty acid. Reaction (1) is catalyzed by cytosolic malate dehydrogenase. Reaction (2) is catalyzed by mitochondrial malate dehydrogenase. (T) designates tricarboxylate anion transporter. Reactions catalyzed by glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the pentose phosphate pathway produce NADPH. CS, citrate synthase ACL, ATP citrate lyase PDH, pyruvate dehydrogenase complex ACC, acetyl-CoA carboxylase FAS, fatty acid synthase.

Shinoda and co-workers have reported the one-step synthesis and anion binding properties of macrocycle 72. Proton NMR titration experiments (in D2O) were used to determine the binding properties of 72 for tricarboxylate anions and revealed that the tricarboxylate 72b was bound with the highest affinity (logfCa = 5.1) [86]. 

In 2005 Schmuck and Schwegmann reported the study of a tripodal molecular flytrap 75 where the pyrrole-guanidinium moieties were appended to a triamide backbone. The receptor was designed to bind tricarboxylate anions and UV and fluorescence titration experiments in water showed that 75 bound citrate and trimesoate with association constants >10 [90]. 

Many chemosensor ensembles were reported by Ans-lyn and coworkers. Compound 14, with three gua-nidinium groups displayed in the same direction (Fig. 5). binds to the citrate tricarboxylate anion. Anionic fluorophore 5-carboxy-fluorescein 15 binds with modest affinity to this receptor and shows increased fluorescence intensity due to the decreased pKa of its phenol group. As citrate is added, the fluorophore is displaced from the receptor, and the emission intensity diminishes. The same fluorophore was used in another sensing ensemble for inositol-1,4,5-triphosphate (IP3), an important second messenger involved in many cell regulatory functions. The fluorophore bound to positively charged hexa-gua-nidinium receptor 16 is displaced by added IP3, and the fluorescence intensity decreases. 

Fig. 4 Logarithms of the association constants of some tricarboxylate anions with differently protonated forms of a macrocycle < (From Ref. [24].)...

Anion-binders Crownophanes 34a and 34b recognized H2PO4" Crownophane 67 Complexed 1,3,5-benzene-tricarboxylate anion... 

Recently, binding constants (log K) of Ugand 59-4H with a variety of di-and tricarboxylate anions were examined by NMR technique in D2O... 

The increased degradation of fat that occurs in insulin deficiency also has serious effects. Some of the fatty acids that accumulate in large quantities are taken up by the liver and used for lipoprotein synthesis (hyperlipidemia), and the rest are broken down into acetyl CoA. As the tricarboxylic acid cycle is not capable of taking up such large quantities of acetyl CoA, the excess is used to form ketone bodies (acetoacetate and p-hydroxy-butyrate see p. 312). As H"" ions are released in this process, diabetics not receiving adequate treatment can suffer severe metabolic acidosis (diabetic coma). The acetone that is also formed gives these patients breath a characteristic odor. In addition, large amounts of ketone body anions appear in the urine (ketonuria). 

Our desire to generate a receptor for dicarboxylate anions came from an appreciation that di- and tricarboxylates play critical roles in numerous metabolic processes including, for instance, those associated with the citric acid and glyoxy-late cycles. They also play important roles in the generation of high-energy... 

The resulting tetraethyl ester on hydrolysis and decarboxylation yields propane-1, 2,3-tricarboxylic acid.155 In this example the malonate anion is generated by using one molar proportion of sodium ethoxide this is Michael s original method. However, these conditions sometimes lead to competing side reactions and the formation of abnormal reaction products. Better yields of the required product are often obtained with small amounts of sodium ethoxide (the so-called catalytic method) or in the presence of a secondary amine (e.g. diethyl-amine, see below). 

Aliphatic tricarboxylic acids such as citric acid exhibit a remarkably high affinity toward the stationary phase of an anion exchanger. Hence, low ionic strength bicarbon-ate/carbonate buffer solutions are not particularly suited as eluents. However, when a sodium hydroxide solution at a comparatively high concentration (c 0.08 mol/L) is used, citric acid may be eluted, and may even be separated from its structural isomer isocitric acid. When the detection of these compounds is carried out via electrical con-... 

Translocation systems of the inner mitochondrial membrane are listed in Table 14-5. Anion translocators are responsible for electroneutral movement of dicarboxylates, tricarboxylates, a-ketoglutarate, glutamate, pyruvate, and inorganic phosphate. Specific electrogenic translocator systems exchange ATP for ADP, and glutamate for aspartate, across the membrane. The metabolic function of the translocators is to provide appropriate substrates (e.g., pyruvate and fatty acids) for mitochondrial oxidation that is coupled to ATP synthesis from ADP and Pj. 

Figure 10.16. Separation of 17 inorganic and organic anions. Conditions same as Fig. 10.15. Peaks I = bromide 2 = nitrate 3 = chromate 4 = iodide 5 = molybdate 6 = phthalate 7 = 1,2,3-tricarboxylate 8 = 1,2-benzenedisulfonate 9 = terephthalate 10 = isophthalate 11 = benzoate 12 = p-toluenesulfonate 13 = 1,2,5-tricarboxylatc 14 = 2-nathphalenesulfonate 15 = 1-naphthalencsulfonate 16 = 3,5-dihydrox-ybenzoato 17 = 2,4-dihydroxybenzoate x = unidentified impurity.

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