Bicarbonate into Carboxyl Groups

When [180]bicarbonate is a substrate, two labeled oxygen atoms enter the oxaloacetate, while the third appears in P . A concerted, cyclic mechanism could explain these results. However, study of kinetic isotope effects,291 use of a substrate with a chiral thio-phospho group,292 and additional lsO exchange studies293 have ruled out this possibility. A transient carboxyl phosphate (Eq. 13-53) is evidently an intermediate.294 295 The incorporation of the lsO from bicarbonate into phosphate is indicated by the asterisks. 

The conversion of acetyl-CoA into malonyl-CoA increases the acidity of the a-hydrogens, and thus provides a better nucleophile for the Claisen condensation. In the biosynthetic sequence, no acy-lated malonic acid derivatives are produced, and no label from [14C]bicarbonate is incorporated, so the carboxyl group introduced into malonyl-CoA is simultaneously lost by a decarboxylation reaction during the Claisen condensation (Figure 3.1). Accordingly, the carboxylation step helps to activate the a-carbon and facilitate Claisen condensation, and the carboxyl is immediately removed on completion of this task. An alternative rationalization is that decarboxylation of the malonyl ester is used to generate the acetyl enolate anion without any requirement for a strong base. 

When worked up sequentially with sodium bisulfite, sodium bicarbonate, and sodium hydroxide, the noncarbohydrate portion divides into fractions rich in aldehyde groups, carboxyl groups, and free phenolic hydroxyl groups, all exhibiting strong aromatic bands in infrared spectra (Figure 5). A fourth fraction remains after extraction by the other three reagents which shows some hydroxyl and aldehydic functionality but mainly aliphatic hydrocarbon structure. This neutral fraction is derived... 

Biotin is the coenzyme required by enzymes that catalyze carboxylation of a carbon adjacent to a carbonyl group. For example, pymvate carboxylase converts pyruvate—the end product of carbohydrate metabolism—to oxaloacetate, a citric acid cycle intermediate (Figure 25.2). Acetyl-CoA carboxylase converts acetyl-CoA into malonyl-CoA, one of the reactions in the anabolic pathway that converts acetyl-CoA into fatty acids (Section 19.21). Biotin-requiring enzymes use bicarbonate (HCOs ) for the source of the carboxyl group that becomes attached to the substrate. 

Step 1 biotin is carboxylated using bicarbonate ion (HCO ") as the source of the carboxyl group. Step 2 the carboxylated biotin is brought into proximity with enzyme-bound acetyl-CoA by a biotin carrier protein. Step 3 the carboxyl group is transferred to acetyl-CoA, forming malonyl-CoA. 

Acetyl-CoA carboxylase (ACC EC 6.4.1.2) is a biotin-dependent carboxylase that produces malonyl-CoA from bicarbonate as a source of carboxyl group and ATP as a source of energy. The reaction catalyzes the conversion of acetyl-CoA into malonyl-CoA through the incorporation of a carboxyl group into the acetyl radical of the acetyl-CoA. This transcarboxylation reaction is performed following the three-step process followed by all biotin-dependent transcarboxylases (Scheme 9.1)... 

For example, pyruvate carboxylase converts pyruvate to oxaloacetate and acetyl-CoA carboxylase converts acetyl-CoA into malonyl-CoA. Biotin-requiring enzymes use bicarbonate (HCO3 ) for the source of the carboxyl group that becomes attached to the a-carbon of the substrate. 

In mammals, biotin serves as an essential cofactor for five carboxylases, each of which catalyses a critical step in intermediary metabolism. All five of the mammalian carboxylases catalyze the incorporation of bicarbonate as a carboxyl group into a substrate and employ a similar catalytic mechanism. 

The high water solubility of carboxylate salts is important in biological systems. The body s bicarbonate-carbonic acid and other buffer systems solubilize carboxylic acids by conversion to carboxylate salts. Intravenous drugs containing the COOH group are usually administered in the form of the carboxylate salt instead of the carboxylic acid to achieve faster absorption into the body. 

The reaction of CO2 with a metal hydride produces formate complexes M-0C(0)H, not formyl derivatives M-C(0)0H, and the insertion into M-C bonds gives the appropriate carboxylate compounds M-0C(0)R. In a similar fashion, the reactions with M-OH and M-OR (R = alkyl, aryl) generate the corresponding bicarbonate M-0C(0)0H and carbonate M-0C(0)0R species, respectively. The reaction of CO2 with a zinc hydroxide moiety is particularly important in biological systems, namely, for the reversible hydration of CO2 to HCOs catalyzed by Zn(ll) in carbonic anyhdrases. Moreover, it has been postulated that the insertion of CO2 into M-O bonds is essential in the co-polymerization of CO2 and epoxides and in the preparation of cyclic carbonates and polycarbo-In a similar vein, the insertion of CO2 into the M-N bond of both main group and transition metal... 

The most widely practiced reactions convert carboxylic acids into esters, amides, carboxylate salts, acid chlorides, and alcohols. Carboxylic acids react with bases to form carboxylate salts, in which the hydrogen of the hydroxyl (-OH) group is replaced with a metal cation. Thus, acetic acid found in vinegar reacts with sodium bicarbonate (baking soda) to form sodium acetate, carbon dioxide, and water ... 

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