Carey - Organic Chemistry - chapt27

Carey - Organic Chemistry - chapt27

(Parte 1 de 7)

CHAPTER 27

The relationship between structure and function reaches its ultimate expression in the chemistry of amino acids, peptides, and proteins.

Amino acids are carboxylic acids that contain an amine function. Under certain conditions the amine group of one molecule and the carboxyl group of a second can react, uniting the two amino acids by an amide bond.

Amide linkages between amino acids are known as peptide bonds,and the product of peptide bond formation between two amino acids is called a dipeptide.The peptide chain may be extended to incorporate three amino acids in a tripeptide,four in a tetrapeptide, and so on. Polypeptidescontain many amino acid units. Proteinsare naturally occurring polypeptides that contain more than 50 amino acid units—most proteins are polymers of 100–300 amino acids.

The most striking thing about proteins is the diversity of their roles in living systems: silk, hair, skin, muscle, and connective tissue are proteins, and almost all enzymes are proteins. As in most aspects of chemistry and biochemistry, structure is the key to function. We’l explore the structure of proteins by first concentrating on their fundamental building block units, the -amino acids. Then, after developing the principles of peptide structure, we’l see how the insights gained from these smaler molecules aid our understanding of proteins.

Amide (peptide) bond

Dipeptide Water H2O

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1052CHAPTER TWENTY-SEVENAmino Acids, Peptides, and Proteins. Nucleic Acids

The chapter concludes with a discussion of the nucleic acids,which are the genetic material of living systems and which direct the biosynthesis of proteins. These two types of biopolymers, nucleic acids and proteins, are the organic chemicals of life.

27.1CLASSIFICATION OF AMINO ACIDS

Amino acids are classified as , , , and so on, according to the location of the amine group on the carbon chain that contains the carboxylic acid function.

Although more than 700 different amino acids are known to occur naturally, a group of 20 of them commands special attention. These 20 are the amino acids that are normally present in proteins and are shown in Figure 27.1 and in Table 27.1. All the amino acids from which proteins are derived are -amino acids, and all but one of these contain a primary amino function and conform to the general structure

The one exception is proline, a secondary amine in which the amino nitrogen is incorporated into a five-membered ring.

Table 27.1 includes three-letter and one-letter abbreviations for the amino acids. Both enjoy wide use.

Our bodies can make some of the amino acids shown in the table. The others, which are called essential amino acids,we have to get from what we eat.

27.2STEREOCHEMISTRY OF AMINO ACIDS

Glycine is the simplest amino acid and the only one in Table 27.1 that is achiral. The -carbon atom is a stereogenic center in all the others. Configurations in amino acids are normally specified by the D, Lnotational system. All the chiral amino acids obtained from proteins have the Lconfiguration at their -carbon atom.

H Proline

RCHCO2 NH3

1-Aminocyclopropanecarboxylic acid:

an -amino acid that is the biologicalprecursor to ethylene in plantsCO2 NH3

3-Aminopropanoic acid: known as -alanine, it is a -amino acid that makes up one of the structural units of coenzyme A

4-Aminobutanoic acid: known as -aminobutyric acid (GABA), it is a -amino acid and is involved in the transmission of nerve impulses

The graphic that opened this chapter is an electrostatic potential map of glycine.

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Amino acids with nonpolar side chains

Amino acids with polar but nonionized side chains Amino acids with acidic side chains

Amino acids with basic side chains

LeucineValine IsoleucineAlanineGlycine Methionine Proline Phenylalanine Tryptophan

GlutamineAsparagine Serine Threonine

Glutamic acidAspartic acid Tyrosine Cysteine

Lysine Arginine Histidine

FIGURE 27.1 Electrostatic potential maps of the 20 common amino acids listed in Table 27.1. Each amino acid is oriented so that its side chain is in the upper left corner. The side chains affect the shape and properties of the amino acids.

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1054CHAPTER TWENTY-SEVENAmino Acids, Peptides, and Proteins. Nucleic Acids

TABLE 27.1 -Amino Acids Found in Proteins Name

Glycine

Alanine

Valine†

Leucine†

Isoleucine†

Methionine† Proline

Phenylalanine† Tryptophan†

(Continued)

Amino acids with nonpolar side chains

Asparagine Amino acids with polar but nonionized side chains

Gly (G)

Ala (A)

Val (V)

Leu (L)

Ile (I)

Met (M) Pro (P)

Phe (F) Trp (W)

Asn (N)

Abbreviation Structural formula*

CHCO2

CH3 NH3 CHCO2

CH3CH2CH NH3 CHCO2 CH3

CHCO2

CH3SCH2CH2 NH3 CHCO2

CH2 NH3 CHCO2

CH2 NH3 CHCO2

*All amino acids are shown in the form present in greatest concentration at pH 7. †An essential amino acid, which must be present in the diet of animals to ensure normal growth.

Learning By Modeling contains electrostatic potential maps of all the amino acids in this table.

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TABLE 27.1 -Amino Acids Found in Proteins (Continued) Name

Serine Threonine†

Aspartic acid

Glutamic acid Tyrosine

Cysteine

Amino acids with acidic side chains Amino acids with polar but nonionized side chains

Lysine†

Amino acids with basic side chains

Ser (S) Thr (T)

Asp (D)

Glu (E) Tyr (Y)

Cys (C)

Lys (K)

Arg (R) His (H)

Abbreviation Structural formula*

CH3CH NH3 CHCO2

HSCH2 NH3 CHCO2

OCCH2 NH3 CHCO2

CHCO2

OCCH2CH2 NH3 CHCO2

HOCH2 NH3 CHCO2

CH2 NH3

NH3 CHCO2

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PROBLEM 27.1What is the absolute configuration (Ror S) at the carbon atom in each of the following L-amino acids?

(a) (c)

(b)

SAMPLE SOLUTION(a) First identify the four groups attached directly to the stereogenic center, and rank them in order of decreasing sequence rule precedence. For L-serine these groups are

Next, translate the Fischer projection of L-serine to a three-dimensional representation, and orient it so that the lowest ranked substituent at the stereogenic center is directed away from you.

In order of decreasing precedence the three highest ranked groups trace an anticlockwise path.

The absolute configuration of L-serine is S.

PROBLEM 27.2Which of the amino acids in Table 27.1 have more than one stereogenic center?

Although all the chiral amino acids obtained from proteins have the Lconfiguration at their carbon, that should not be taken to mean that D-amino acids are unknown. In fact, quite a number of D-amino acids occur naturally. D-Alanine, for example, is a

HOCH2 CO2 NH3

CH2OH C

HOCH2

HOCH2 CO2

CH2SH L-Cysteine

CH2CH2SCH3 L-Methionine

CH2OH L-Serine

Glycine(achiral) Fischer projection of an L-amino acid

1056CHAPTER TWENTY-SEVENAmino Acids, Peptides, and Proteins. Nucleic Acids

BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website constituent of bacterial cell walls. The point is that D-amino acids are not constituents of proteins.

Anew technique for dating archaeological samples called amino acid racemization(AAR) is based on the stereochemistry of amino acids. Over time, the configuration at the -carbon atom of a protein’s amino acids is lost in a reaction that follows firstorder kinetics. When the carbon is the only stereogenic center, this process corresponds to racemization. For an amino acid with two stereogenic centers, changing the configuration of the carbon from Lto Dgives a diastereomer. In the case of isoleucine, for example, the diastereomer is an amino acid not normally present in proteins, called alloisoleucine.

By measuring the L-isoleucine/D-alloisoleucine ratio in the protein isolated from the eggshells of an extinct Australian bird, a team of scientists recently determined that this bird lived approximately 50,0 years ago. Radiocarbon (14C) dating is not accurate for samples older than about 35,0 years, so AAR is a useful addition to the tools available to paleontologists.

27.3ACID–BASE BEHAVIOR OF AMINO ACIDS

The physical properties of a typical amino acid such as glycine suggest that it is a very polar substance, much more polar than would be expected on the basis of its formula- tion as H2NCH2CO2H. Glycine is a crystalline solid; it does not melt, but on being heated it eventually decomposes at 233°C. It is very soluble in water but practically insoluble in nonpolar organic solvents. These properties are attributed to the fact that the stable form of glycine is a zwitterion,or innersalt.

The equilibrium expressed by the preceding equation lies overwhelmingly to the side of the zwitterion.

Glycine, as well as other amino acids, is amphoteric,meaning it contains an acidic functional group and a basic functional group. The acidic functional group is the ammo- nium ion ; the basic functional group is the carboxylate ion ±CO2 . How do we know this? Aside from its physical properties, the acid–base properties of glycine, as illustrated by the titration curve in Figure 27.2, require it. In a strongly acidic medium the species present is . As the pH is raised, a proton is removed from this species. Is the proton removed from the positively charged nitrogen or from the carboxyl group? We know what to expect for the relative acid strengths of and RCO2H. A typical ammonium ion has pKa 9, and a typical carboxylic acid has pKa 5. The

RNH3

L-Isoleucine

CO2

CH2CH3

D-Alloisoleucine

CO2

CH2CH3

The zwitterion is also often referred to as a dipolar ion. Note, however, that it is not an ion, but a neutral molecule.

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measured pKafor the conjugate acid of glycine is 2.35, a value closer to that expected for deprotonation of the carboxyl group. As the pH is raised, a second deprotonation step, corresponding to removal of a proton from nitrogen of the zwitterion, is observed.

The pKaassociated with this step is 9.78, much like that of typical alkylammonium ions.

Thus, glycine is characterized by two pKavalues: the one corresponding to the more acidic site is designated pKa1, the one corresponding to the less acidic site is des- ignated pKa2. Table 27.2 lists pKa1and pKa2values for the -amino acids that have neutral side chains, which are the first two groups of amino acids given in Table 27.1. In all cases their pKavalues are similar to those of glycine. Table 27.2 includes a column labeled pI, which gives isoelectric pointvalues. The isoelectric point is the pH at which the amino acid bears no net charge; it corresponds to the pH at which the concentration of the zwitterion is a maximum. For the amino acids in Table 27.2 this is the average of pKa1and pKa2and lies slightly to the acid side of neutrality.

Some amino acids, including those listed in the last two sections of Table 27.1, have side chains that bear acidic or basic groups. As Table 27.3 indicates, these amino acids are characterized by three pKavalues. The “extra” pKavalue (it can be either pKa2 or pKa3) reflects the nature of the function present in the side chain. The isoelectric points of the amino acids in Table 27.3 are midway between the pKavalues of the monocation and monoanion and are well removed from neutrality when the side chain bears a car- boxyl group (aspartic acid, for example) or a basic amine function (lysine, for example).

Zwitterion; predominant species in solutions near neutrality

Species presentin strong baseSpecies present in strong acid

1058CHAPTER TWENTY-SEVENAmino Acids, Peptides, and Proteins. Nucleic Acids

Equivalents of base added 0.4 pKa1 = 2.3 pKa2 = 9.8

FIGURE 27.2 The titration curve of glycine. At pH values less than pKa1, is the major species present. At pH values between pKa1and pKa2, the principal species is the zwitterion

. The concentration of the zwitterion is a maximum at the isoelectric point pI. At

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PROBLEM 27.3Write the most stable structural formula for tyrosine: (a)In its cationic form(c)As a monoanion (b)In its zwitterionic form(d)As a dianion

SAMPLE SOLUTION(a) The cationic form of tyrosine is the one present at low pH. The positive charge is on nitrogen, and the species present is an ammonium ion.

HO CH2CHCO2H NH3

TABLE 27.2Acid-Base Properties of Amino Acids with Neutral Side Chains

Amino acid

Glycine Alanine Valine Leucine Isoleucine Methionine Proline Phenylalanine Tryptophan Asparagine Glutamine Serine Threonine pKa1* pKa2*

*In all cases pKa1 corresponds to ionization of the carboxyl group; pKa2 corresponds to deprotonation of the ammonium ion.

TABLE 27.3Acid-Base Properties of Amino Acids with Ionizable Side Chains

Amino acid

Aspartic acid Glutamic acid Tyrosine Cysteine

Lysine Arginine Histidine pKa1* pKa2 pKa3

*In all cases pKa1 corresponds to ionization of the carboxyl group of RCHCO2H. W

NH3

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1060CHAPTER TWENTY-SEVENAmino Acids, Peptides, and Proteins. Nucleic Acids ELECTROPHORESIS

Electrophoresis is a method for separation and purification that depends on the movement of charged particles in an electric field. Its principles can be introduced by considering the electrophoretic behavior of some representative amino acids. The medium is a cellulose acetate strip that is moistened with an aqueous solution buffered at a particular pH. The opposite ends of the strip are placed in separate compartments containing the buffer, and each compartment is connected to a source of direct electric current (Figure 27.3a). If the buffer solution is more acidic than the isoelectric point (pI) of the amino acid, the amino acid has a net positive charge and migrates toward the negatively charged electrode. Conversely, when the buffer is more basic than the pI of the amino acid, the amino acid has a net negative charge and migrates toward the positively charged electrode. When the pH of the buffer corresponds to the pI, the amino acid has no net charge and does not migrate from the origin.

Thus if a mixture containing alanine, aspartic acid, and lysine is subjected to electrophoresis in a buffer that matches the isoelectric point of alanine (pH 6.0), aspartic acid (pI 2.8) migrates toward the positive electrode, alanine remains at the origin, and lysine (pI 9.7) migrates toward the negative electrode (Figure 27.3b).

NH3

Aspartic acid (monoanion)

CH3CHCO2

NH3

Alanine (neutral)

NH3

Lysine (monocation)

A mixture of amino acids

at a pH of 6.0. At this pH aspartic acidexists as its 1 ion, alanine as its zwitterion, and
lysineas its 1 ion.

Application of an electric current causes the negatively charged ions to migrate to the electrode, and the positively charged ions to migrate to the electrode. The zwitterion, with a net charge of zero, remains at its original position.

—Cont.

FIGURE 27.3 Application of electrophoresis to the separation of aspartic acid, alanine, and lysine according to their charge type at a pH corresponding to the isoelectric point (pI) of alanine.

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PROBLEM 27.4Write structural formulas for the principal species present when the pH of a solution containing lysine is raised from 1 to 9 and again to 13.

The acid–base properties of their side chains are one way in which individual amino acids differ. This is important in peptides and proteins, where the properties of the substance depend on its amino acid constituents, especially on the nature of the side chains. It is also important in analyses in which a complex mixture of amino acids is separated into its components by taking advantage of the differences in their protondonating and proton-accepting abilities.

(Parte 1 de 7)

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