Acid-base chemistry amino acids

In this section, enzymes in the EC 2.4. class are presented that catalyze valuable and interesting reactions in the field of polymer chemistry. The Enzyme Commission (EC) classification scheme organizes enzymes according to their biochemical function in living systems. Enzymes can, however, also catalyze the reverse reaction, which is very often used in biocatalytic synthesis. Therefore, newer classification systems were developed based on the three-dimensional structure and function of the enzyme, the property of the enzyme, the biotransformation the enzyme catalyzes etc. [88-93]. The Carbohydrate-Active enZYmes Database (CAZy), which is currently the best database/classification system for carbohydrate-active enzymes uses an amino-acid-sequence-based classification and would classify some of the enzymes presented in the following as hydrolases rather than transferases (e.g. branching enzyme, sucrases, and amylomaltase) [91]. Nevertheless, we present these enzymes here because they are transferases according to the EC classification. 

Additional aspects of the acid-base chemistry of amino acids and proteins are considered in Chapter 3, Section A and Chapter 6, Section E. The student may find it appropriate to study these sections at this time and to work the associated study problems. 

You probably studied acid-base chemistry as part of your undergraduate studies. However, acids and bases play such a key role in medicine and physiology that we believe the subject merits another look. The central theme in acid-base chemistry is relatively simple. Acids donate hydrogen ions to bases. The uses of this reaction are myriad in variation and in application. By controlling the acid-base conditions, you can ensure that a medication stays in solution. If the acid content of blood changes by a tiny amount, the patient dies. The acidic and/or basic properties of amino acids located in the active site of an enzyme catalyze a staggering number of chemical transformations which are essential for life. 

Understanding the Acid-Base Chemistry of Amino Acids... 

Evans, C. A., and Rabenstein, D. L. (1974). J. Amer. Chem. Soc. 96, 7312. Nuclear Magnetic Resonance Studies of the Acid-Base Chemistry of Amino Acids and Peptides. II. Dependence of the Acidity of the C-Terminal Carboxyl Group on the Conformation of the C-Terminal Peptide Bond. 

Answer Benzocaine, which lacks an aliphatic amino group needed for salt formation, is practically insoluble in water. Protonation of the aromatic amino group in benzocaine results in a salt with a pKa of 2.78, which is too acidic and, therefore, unsuitable for preparation of a parenteral dosage form for injection. Based on the acid-base chemistry principle, an aromatic amino group is a weak base, because its nonbounded elections are delocalized into the aromatic ring. Thus, an aromatic amine salt, such as benzocaine, will not hold onto its proton as tightly as an aliphatic amine salt and, therefore, will readily release the proton when dissolved in water. 

The importance of heterocycles in life was recognized as the nascent stage of organic chemistry two centuries ago with isolation of alkaloids such as morphine from poppy seeds, quinine from cinchona barks, and camptothecin from the Chinese joy tree. Today, heterocycles are found in numerous fields of biochemical and physiological such as photosynthesis, amino acids, DNA bases, vitamins, endogenous neurotransmitters, and so on. 

The acid-base chemistry of amino acids is more complicated than shown in Equations 16.48 and 16.49, however. Because the COOH group can act as an acid and the NH2 group can act as a base, amino acids undergo a self-contained Bronsted-Lowry acid-base reaction in which the proton of the carboxyl group is transferred to the basic nitrogen atom ... 

WE BEGIN THIS CHAPTER with a study of amino acids, compounds whose chemistry is built on amines (Chapter 10) and carboxylic acids (Chapter 13). We concentrate in particular on the acid-base properties of amino acids because these properties are so important in determining many of the properties of proteins, polymers of amino acids that have many functions in living organisms. With this understanding of the chemistry of amino acids, we then examine the structure of proteins themselves. 

The acid-base chemistry of amino acids and various cofactors are certainly not the only biological structures whose activity depends upon the protonation state. Even DNA responds to pH effects due to acidic and basic sites within its structure. At physiological pH the four heterocyclic bases of nucleotides are neutral, but as the pH is raised, thymine and uridine will undergo deprotonation near pH 10. As the pH is lowered, cytidine will become protonated around pH 6. This protonation has been used to control DNA triple helix formation, as shown in the following Connections highlight. 

FIGURE 23.5 An amine and a carboxylic acid must undergo acid-base chemistry to give an ammonium salt of the acid. In amino acids, an intramolecular version of the same reaction gives a zwitterion. 

Second, there is a problem of specificity. Suppose we want to make the trivial dipeptide Ala Leu. Even if we can avoid simple acid-base chemistry, random reaction between these two amino acids will give us at least the four possible dimeric molecules, and in practice, other larger peptides will be produced as well (Fig. 23.41). 

Asymmetric synthesis of unnatural j8-amino acids derivatives based on azide chemistry is known. Enantioselective desymmetrization of mera-anhydride 293 mediated by cinchona alkaloids gives optically active monomethylester 294. This compound was converted into the acyl azide, which underwent Curtius degradation followed by alcoholysis of the intermediate isocyanate affording 8-amino acid derivative 295 in high enantiomeric excess. The authors observed that Grubbs catalyst was able to polymerize norbomene-type monomer 295 affording the corresponding polymer 296 in quantitative yield (Scheme 3.45). 

Jurecka, P., Sponer, J., Cerny, J., 8c Hobza, P. (2006). Benchmark database of accurate (MP2 and CCSD(T) complete basis set limit) interaction energies of small model complexes, DNA base pairs, and amino acid pairs. Physical Chemistry Chemical Physics, 8,1985-1993. 

CSPs [27], In biological systems, the TPI model was first successfully applied by Ogston to explain the enzymatic formation of ketoglutarate from achiral citrate and decarboxylation of L-serine to glycine by enzymes [28], Based on the same principle, Shallenberger et al. [29] established a similar model to explain how a sweet-taste receptor of the tongue distinguished D- and L-amino acids. In medicinal chemistry, the TPI model is a key element in structure-activity relationship studies [30],... 

One of the best methods for synthesizing amino acids is based on the chemistry of malonate esters (Section 22.17) and a modification of the Gabriel synthesis of amines (Section 23.7). Diethyl acetamidomalonate has a nitrogen atom bonded to the a-carbon of the malonate ester. This nitrogen eventually becomes the nitrogen of the final amino acid product. 

The differences in the amino acid chemistry of the hide coUagen and the hair keratin are the basis of the lime-sulfide unhairing system. Hair contains the amino acid cystine. This sulfur-containing amino acid cross-links the polypeptide chains of mature hair proteins. In modem production of bovine leathers the quantity of sulfide, as Na2S or NaSH, is normally 2—4% based on the weight of the hides. The lime is essentially an unhmited supply of alkah buffered to pH 12—12.5. The sulfide breaks the polypeptide S—S cross-links by reduction. Unhairing without sulfide may take several days or weeks. The keratin can be easily hydrolyzed once there is a breakdown in the hair fiber stmcture and the hair can be removed mechanically. The coUagen hydrolysis is not affected by the presence of the sulfides (1—4,7). 

Pyrimidine and imidazole rings are particularly important in biological chemistry. Pyrimidine, for instance, is the parent ring system in cytosine, thymine, and uracil, three of the five heterocyclic amine bases found in nucleic acids An aromatic imidazole ring is present in histidine, one of the twenty amino acids found in proteins. 

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