Lippincott’s Illustrated Reviews: Biochemistry, 3rd Editionby Pamela C. Champe and Richard A. HarveyLippincott, Williams & Wilkins, Baltimore, MD 2003 1

Amino Acids 1

Figure 1.1Structural features of amino acids(shown in their fully protonated form).

CH3N COOH

Common to all α-amino acids of proteins

R

Side chain is distinctivefor each amino acid

Aminogroup

Carboxylgroup

α

UNIT I:Protein Structure

and Function

I. OVERVIEW

Proteins are the most abundant and functionally diverse molecules in liv-ing systems. Virtually every life process depends on this class ofmolecules. For example, enzymes and polypeptide hormones direct andregulate metabolism in the body, whereas contractile proteins in musclepermit movement. In bone, the protein collagen forms a framework forthe deposition of calcium phosphate crystals, acting like the steel cablesin reinforced concrete. In the bloodstream, proteins such as hemoglobinand plasma albumin shuttle molecules essential to life, whereasimmunoglobulins destroy infectious bacteria and viruses. In short, pro-teins display an incredible diversity of functions, yet all share the com-mon structural feature of being linear polymers of amino acids. Thischapter describes the properties of amino acids; Chapter 2 explores howthese simple building blocks are joined to form proteins that have uniquethree-dimensional structures, making them capable of performing spe-cific biologic functions.

II. STRUCTURE OF THE AMINO ACIDS

Although more than 300 different amino acids have been described innature, only twenty are commonly found as constituents of mammalianproteins. [Note: These are the only amino acids that are coded for byDNA, the genetic material in the cell (see p. xxx).] Each amino acid(except for proline, which is described on p. xxx) has a carboxyl group,an amino group, and a distinctive side chain (“R-group”) bonded to theα-carbon atom (Figure 1.1). At physiologic pH (approximately pH = 7.4)the carboxyl group is dissociated, forming the negatively charged car-boxylate ion (–COO– ), and the amino group is protonated (–NH3

+). Inproteins, almost all of these carboxyl and amino groups are combined inpeptide linkage, and are not available for chemical reaction (except forhydrogen bond formation (see Figure 2.10, p. xxx). Thus, it is the nature

of the side chains that ultimately dictates the role an amino acid plays ina protein. It is therefore useful to classify the amino acids according tothe properties of their side chains—that is, whether they are nonpolar orpolar (uncharged, acidic or basic; Figures 1.2 and 1.3).

A. Amino acids with nonpolar side chains

Each of these amino acids has a nonpolar side chain that does notbind or give off protons, or participate in hydrogen or ionic bonds(see Figure 1.2). The side chains of these amino acids can bethought of as "oily" or lipid-like, a property that promotes hydropho-bic interactions (see Figure 2.9, p. xxx).

1. Location of nonpolar amino acids in proteins: In proteins foundin aqueous solutions, the side chains of the nonpolar amino acidstend to cluster together in the interior of the protein (Figure 1.4).

2 1. Amino Acids

C+H3N COOH

H

HpK2 = 9.6 pK1 = 2.3

Glycine

C+H3N COOH

H

CH3

Alanine Valine

C+H3N COOH

H

CH2

Methionine

CH2

C+H3N COOH

H

CH2

Phenylalanine

C+H3N COOH

H

CH2

Tryptophan

C

CHNH

S

CH3

COOH

H

Proline

C

CH2

+H2N

CH2

H2C

NONPOLAR SIDE CHAINS

Figure 1.2Classification of the twenty amino acids found in proteins according to the charge and polarity of their side chains is shown here and continues in Figure 1.3. Each amino acid is shown in its fully protonated form with dissociable hydrogen ions represented in bold print. The pK values for the α-carboxyl and α-amino groups of the nonpolar amino acids are similar to those shown for glycine.

C+H3N COOH

H

CHCH3H3C

C+H3N COOH

H

CH2

Leucine

CHCH3H3C

C+H3N COOH

H

CH3

CH CH3

CH2

Isoleucine

II. Structure of the Amino Acids 3

C+H3N COOH

H

CH2

Glutamic acid

OHO

CH2

C

ACIDIC SIDE CHAINS

pK1 = 2.1

pK2 = 4.3

pK3 = 9.7C+H3N COOH

H

CH2

Aspartic acid

OHOC

pK2 = 3.9

pK3=9.8

C+H3N COOH

H

CH2

CH2

BASIC SIDE CHAINS

pK1 = 2.2

C+H3N COOH

H

CH2

pK3 = 9.2

CH

NHCH

+HN

C

pK1 = 1.8

pK2 = 6.0

CH2

CH2

NH3+ pK3 = 10.5

C+H3N COOH

H

CH2

CH2

CH2

N

pK3 = 12.5

H

C

NH2

NH2+

C+H3N COOH

H

CH2

NH2O

C+H3N COOH

H

CH2

Asparagine Glutamine

NH2O

CH2

C

UNCHARGED POLAR SIDE CHAINS

C+H3N COOH

H

CH2

Cysteine

SHpK3=10.8 pK2 = 8.3

pK1 = 1.7

C+H3N COOH

H

Serine

C

H

H OH

C+H3N COOH

H

Threonine

C

CH3

H OH

C+H3N COOH

H

CH2

Tyrosine

OH

pK2 = 9.1

pK3 = 10.1

pK1 = 2.2

C

CH2

C

ACIDIC SIDE CHAINS

H

OC

pK2 = 3.9

C+H3N COOH

H

CH2

CH2

BASIC SIDE CHAINS

pK1 = 2.2

C+H3N COOH

H

CH2

Histidine

pK3 = 9.2

CH

NHCH

+HN

C

pK1 = 1.8

pK2 = 6.0

CH2

CH2

NH3+ pK3 = 10.5

Lysine

pK2 = 9.0

C+H3N COOH

H

CH2

CH2

CH2

N

pK3 = 12.5

Arginine

H

C

NH2

NH2+

C+H3N COOH C+H3N COOH

H

CH2

Asparagine Glutamine

NH2O

CH2

C

UNCHARGED POLAR SIDE CHAINS

CH2pK3=10.8

C

C OH

C+H3N COOH

H

C

CH3

H OH

+H3N

Tyrosine

pK3 = 10.1

C

Figure 1.3Classification of the twenty amino acids found in proteins according to the charge and polarity of their side chains (continued from Figure 1.2).

pK2 = 9.2

Figure 1.4Location of nonpolar amino acidsin soluble and membrane proteins.

Soluble protein Membrane protein

Polar amino acids( ) cluster onthe surface of soluble proteins

Nonpolar aminoacids ( ) cluster on the surface of membrane proteins

Cellmembrane

Figure 1.5Comparison of the imino group found in proline with the α-aminogroup found in other amino acids such as alanine.

C+H3N COOH

H

CH3

Alanine

COOH

H

Proline

C

CH2

+H2N

H2C

Amino group

Imino group

CH2

Figure 1.6Hydrogen bond between the phenolic hydroxyl group of tyrosine and another molecule containing a carbonyl group.

C+H3N COOH

CH2

Tyrosine

Carbonyl group

Hydrogen bond

O

C

O

H

H

This phenomenon is due to the hydrophobicity of the nonpolar R-groups, which act much like droplets of oil that coalesce in anaqueous environment. The nonpolar R-groups thus fill up the inte-rior of the folded protein, and help give it its three-dimensionalshape. [Note: In proteins that are located in a hydrophobic envi-ronment such as a membrane, the nonpolar R-groups are foundon the surface of the protein, interacting with the lipid environment(see Figure 1.4).] The importance of these hydrophobic interac-tions in stabilizing protein structure is discussed on p. xxx.

2. Proline: The side chain of proline and its α-amino group form aring structure, and thus proline differs from other amino acids inthat it contains an imino group, rather than an amino group(Figure 1.5).

B. Amino acids with uncharged polar side chains

These amino acids have zero net charge at neutral pH, although theside chains of cysteine and tyrosine can lose a proton at an alkalinepH (see Figure 1.3). Serine, threonine, and tyrosine each contain apolar hydroxyl group that can participate in hydrogen bond forma-tion (Figure 1.6). The side chains of asparagine and glutamine eachcontain a carbonyl group and an amide group, both of which can alsoparticipate in hydrogen bonds.

1. Disulfide bond: The side chain of cysteine contains a sulfhydrylgroup (–SH), which is an important component of the active siteof many enzymes. In proteins, the –SH groups of two cysteinescan become oxidized to form a dimer, cystine, which contains acovalent cross-link called a disulfide bond (–S–S–) (See p. xxxfor a further discussion of disulfide bond formation.)

2. Side chains as sites of attachment for other compounds: Serine,threonine, and, rarely, tyrosine contain a polar hydroxyl group thatcan serve as a site of attachment, for structures such as a phos-phate group. [Note: The side chain of serine is an important com-ponent of the active site of many enzymes.] In addition, the amidegroup of asparagine, as well as the hydroxyl group of serine orthreonine, can serve as a site of attachment of oligosaccharidechains in glycoproteins (see p. xxx).

C. Amino acids with acidic side chains

The amino acids aspartic and glutamic acid are proton donors. Atneutral pH the side chains of these amino acids are fully ionized, con-taining a negatively charged carboxylate group (–COO–). They aretherefore called aspartate or glutamate to emphasize that these aminoacids are negatively charged at physiologic pH (see Figure 1.3).

D. Amino acids with basic side chains

The side chains of the basic amino acids accept protons (see Figure1.3. At physiologic pH the side chains of lysine and arginine are fullyionized and positively charged. In contrast, histidine is weakly basic,

4 1. Amino Acids

Figure 1.7Abbreviations and symbols for the commonly occurring amino acids.

Cysteine = Cys = CHistidine = His = HIsoleucine = Ile = IMethionine = Met = MSerine = Ser = SValine = Val = V

Alanine = Ala = AGlycine = Gly = GLeucine = Leu = LProline = Pro = PThreonine = Thr = T

Arginine = Arg = R (“aRginine”) Asparagine = Asn = N (contains N) Aspartate = Asp = D ("asparDic") Glutamate = Glu = E ("glutEmate") Glutamine = Gln = Q (“Q-tamine”) Phenylalanine = Phe = F (“Fenylalanine”) Tyrosine = Tyr = Y (“tYrosine”) Tryptophan = Trp = W (double ring in the molecule)

Aspartate or = Asx = B (near A) asparagine Glutamate or = Glx = Zglutamine

Lysine = Lys = K (near L) Undetermined = X

amino acid

Unique first letter:

Most commonly ocurring amino acids have priority:

Similar sound names:

Letter close to initial letter:

1

2

3

4

Figure 1.8D and L forms of alanine are mirror images.

H3C

HOOC

D-Alanine

H C NH3+

CH3

COOH

L-Alanine

HC+H3N

and the free amino acid is largely uncharged at physiologic pH.However, when histidine is incorporated into a protein, its side chaincan be either positively charged or neutral, depending on the ionicenvironment provided by the polypeptide chains of the protein. [Note:This is an important property of histidine that contributes to the role itplays in the functioning of proteins such as hemoglobin (see p. xxx).]

E. Abbreviations and symbols for the commonly occurring amino acids

Each amino acid name has an associated three-letter abbreviationand a one-letter symbol (Figure 1.7). The one-letter codes aredetermined by the following rules:

1. Unique first letter: If only one amino acid begins with a particularletter, then that letter is used as its symbol. For example,I = isoleucine.

2. Most commonly occurring amino acids have priority: If morethan one amino acid begins with a particular letter, the most com-mon of these amino acids receives this letter as its symbol. Forexample, glycine is more common than glutamate, so G = glycine.

3. Similar sounding names: Some one-letter symbols sound like theamino acid they represent. For example, F = phenylalanine, or W= tryptophan (“twyptophan” as Elmer Fudd would say).

4. Letter close to initial letter: For the remaining amino acids, a one-letter symbol is assigned that is as close in the alphabet as possi-ble to the initial of the amino acid. Further, B is assigned to Asx,signifying either aspartic acid or asparagine; Z is assigned to Glx,signifying either glutamic acid or glutamine; and X is assigned toan unidentified amino acid.

F. Optical properties of amino acids

The α-carbon of each amino acid is attached to four different chemi-cal groups and is therefore a chiral or optically active carbon atom.Glycine is the exception because its α-carbon has two hydrogensubstituents and therefore is optically inactive. [Note: Amino acidsthat have an asymmetric center at the α-carbon can exist in twoforms, designated D and L, that are mirror images of each other(Figure 1.8). The two forms in each pair are termed stereoisomers,optical isomers, or enantiomers. All the amino acids found in pro-teins are of the L-configuration. However, D-amino acids are found insome antibiotics and in bacterial cell walls. (See p. xxx for a discus-sion of D-amino acid metabolism.)

III. ACID/BASE PROPERTIES OF AMINO ACIDS

Amino acids in aqueous solution contain weakly acidic α-carboxylgroups and weakly basic α-amino groups. In addition, each of the acidicand basic amino acids contains an ionizable group in its side chain.Thus, both free amino acids and some amino acids combined in pep-tide linkages can act as buffers. The quantitative relationship between

III. Acid/Base Properties of Amino Acids 5

Figure 1.9Titration curve of acetic acid.

0 3 4 5 6 70

0.5

1.0

pH

Eq

uiv

alen

tsO

H–

add

ed

Buffer region

CH3COOH CH3COO–

H20

I(acetic acid, HA)

II (acetate, A–)

pKa = 4.8[I] = [II]

OH–

H+

[I] > [II]

[II] > [I]

the concentration of a weak acid (HA) and its conjugate base (A–) isdescribed by the Henderson-Hasselbalch equation.

A. Derivation of the equation

Consider the release of a proton by a weak acid represented by HA:

→HA ← H+ + A–

weak proton salt formacid or conjugate base

The “salt” or conjugate base, A–, is the ionized form of a weakacid. By definition, the dissociation constant of the acid, Ka, is

[Note: The larger the Ka, the stronger the acid, because most ofthe HA has been converted into H+ and A–. Conversely, thesmaller the Ka, the less acid has dissociated, and therefore theweaker the acid.] By solving for the [H+] in the above equation,taking the logarithm of both sides of the equation, multiplying bothsides of the equation by –1, and substituting pH = – log [H+ ] andpKa = – log Ka, we obtain the Henderson-Hasselbalch equation:

B. Buffers

A buffer is a solution that resists change in pH following the additionof acid or base. A buffer can be created by mixing equal concentra-tions of a weak acid (HA) and its conjugate base (A– ). [Note: If theamounts of HA and A– are equal, the pH is equal to the pKa.] If acidis added to such a solution, A– can neutralize it, in the processbeing converted to HA. If a base is added, HA can neutralize it, inthe process being converted to A–. A conjugate acid/base pair canserve as an effective buffer when the pH of a solution is withinapproximately ± 1 pH unit of the pKa of the weak acid, whereasmaximum buffering capacity occurs at a pH equal to the pKa. Asshown in Figure 1.9, a solution containing acetic acid (HA =CH3–COOH) and acetate (A– = CH3 – COO– ) with a pKa of 4.8resists a change in pH from pH 3.8 to 5.8, with maximum bufferingat pH = 4.8. [Note: At pH values less than the pKa, the protonatedacid form (CH3 –COOH) is the predominant species. At pH valuesgreater than the pKa, the deprotonated form (CH3–COO–) is the pre-dominant species in solution.]

pH pKa log[A–][HA]

+

Ka[A–]

[HA][H+]

6 1. Amino Acids

C. Titration of alanine

1. Dissociation of the carboxyl group: The titration curve of an aminoacid can be analyzed in the same way as described for acetic acid.For example, consider alanine, which contains both a carboxyl andan amino group. At a low (acidic) pH, both of these groups areprotonated (shown in Figure 1.10). As the pH of the solution israised, the –COOH group of form I can dissociate by donating aproton to the medium. The release of a proton results in the forma-tion of the carboxylate group, –COO–. This structure is shown asform II, which is the dipolar form of the molecule (see Figure 1.10).[Note: This form is also called a zwitterion and is the isoelectricform of alanine—that is, it has an overall charge of zero.]

2. Application of the Henderson-Hasselbalch equation: The disso-ciation constant of the carboxyl group is called K1, rather than Ka,because the molecule contains a second titratable group. TheHenderson-Hasselbalch equation can be used to analyze the dis-sociation of the carboxyl group of alanine, in the same way asdescribed for acetic acid.

where I is the fully protonated form of alanine, and II is the iso-electric form of alanine (Figure 1.10). This equation can be re-arranged and converted to its logarithmic form to yield:

3. Dissociation of the amino group: The second titratable group ofalanine is the amino (–NH3

+) group shown in Figure 1.10. This isa much weaker acid than the –COOH group, and therefore has amuch smaller dissociation constant, K2. [Note: Its pKa is therefore

pH pK1 log[II][I]

+

K1[II]

[I][H+]

III. Acid/Base Properties of Amino Acids 7

Figure 1.10Ionic forms of alanine in acidic, neutral, and basic solutions.

COOH

I

Alanine in acid solution (pH less than 2)

Net charge = +1

CH3

C+H3N

H

COO–

II

Alanine in neutral solution (pH approximately 6)

Net charge = 0

(isoelectric form)

CH3

C+H3N

H

COO–

III

Alanine in basic solution (pH greater than 10)

Net charge = –1

CH3

CH2N

HH20OH–

H+

H20OH–

H+

pK1 = 2.3 pK2 = 9.1

larger.] Release of a proton from the protonated amino group ofform II results in the fully deprotonated form of alanine, form III(see Figure 1.10).

4. pKs of alanine: The sequential dissociation of protons from thecarboxyl and amino groups of alanine is summarized in Figure1.10. Each of the titratable groups has a pKa that is numericallyequal to the pH at which exactly half of the protons have beenremoved from that group. The pKa for the most acidic group(–COOH) is pK1; the pKa for the next most acidic group (–NH3

+)is pK2.

5. Titration curve of alanine: By applying the Henderson-Hasselbalch equation to each dissociable acidic group, it is possi-ble to calculate the complete titration curve of a weak acid. Figure1.11 shows the change in pH that occurs during the addition ofbase to the fully protonated form of alanine (I) to produce the com-pletely deprotonated form (III). Note the following:

a. Buffer pairs: The –COOH/–COO– pair can serve as a buffer inthe pH region around pK1, and the – NH3

+/– NH2 pair canbuffer in the region around pK2.

b. When pH = pK: When the pH is equal to pK1 (2.3), equalamounts of forms I and II of alanine exist in solution. When thepH is equal to pK2 (9.1), equal amounts of forms II and III arepresent in solution.

c. Isoelectric point: At neutral pH, alanine exists predominantlyas the dipolar form II in which the amino and carboxyl groupsare ionized, but the net charge is zero. The isoelectric point(pI) is the pH at which an amino acid is electrically neutral—that is, where the sum of the positive charges equals the sumof the negative charges. [Note: For an amino acid such as ala-nine, which has only two dissociable hydrogens (one from theα-carboxyl and one from the α-amino group), the pI is theaverage of pK1 and pK2 (pI = [2.3 + 9.1]/2 = 5.7, see Figure1.10). The pI is thus midway between pK1 (2.3) and pK2 (9.1).It corresponds to the pH where structure II (with a net charge ofzero) predominates, and at which there are also equal amountsof form I (net charge of +1) and III (net charge of –1).]

6. Net charge of amino acids at neutral pH: At physiologic pH, allamino acids have a negatively charged group (– COO–) and apositively charged group (– NH3

+), both attached to the α-carbon.[Note: Glutamate, aspartate, histidine, arginine, and lysine haveadditional potentially charged groups in their side chains.]Substances such as amino acids that can act either as an acid ora base are defined as amphoteric, and are referred to asampholytes (amphoteric electrolytes).

D. Other applications of the Henderson-Hasselbalch equation

The Henderson-Hasselbalch equation can be used to calculate howthe pH of a physiologic solution responds to changes in the concen-

8 1. Amino Acids

Figure 1.11The titration curve of alanine.

0 2 4 6 8 100

1.0

2.0

pH

Eq

uiv

alen

tsO

H–

add

ed

pK2 = 9.1

[II] = [III]

0.5

1.5

pK1 = 2.3

[I] = [II]

pI = 5.7

Region of buffering

Region of buffering

tration of weak acid and/or its corresponding “salt” form. For example,in the bicarbonate buffer system, the Henderson-Hasselbalch equa-tion predicts how shifts in [HCO3

–] and pCO2 influence pH (Figure1.12A). The equation is also useful for calculating the abundance ofionic forms of acidic and basic drugs. For example, most drugs areeither weak acids or weak bases (Figure 1.12B). Acidic drugs (HA)release a proton (H+), causing a charged anion (A–) to form.

HA H+ + A–

Weak bases (BH+) can also release a H+. However, the protonatedform of basic drugs is usually charged, and loss of a proton pro-duces the uncharged base (B).

BH+ B + H+

A drug passes through membranes more readily if it is uncharged.Thus, for a weak acid, the uncharged HA can permeate throughmembranes, and A– cannot. For a weak base such as morphine, theuncharged form, B, penetrates through the cell membrane, and BH+

does not. Therefore, the effective concentration of the permeableform of each drug at its absorption site is determined by the relativeconcentrations of the charged and uncharged forms. The ratiobetween the two forms is, in turn, determined by the pH at the siteof absorption, and by the strength of the weak acid or base, which isrepresented by the pKa of the ionizable group. The Henderson-Hasselbalch equation is useful in determining how much drug isfound on either side of a membrane that separates two compart-ments that differ in pH, for example, the stomach (pH 1.0 –1.5) andblood plasma (pH 7.4).

IV. CONCEPT MAPS

Many students find biochemistry a blur of myriad facts or equationsmerely to be memorized. Details provided to enrich understanding,inadvertently turn into distractions. What seems to be missing is a roadmap—a guide that provides the student with an intuitive understandingof how various topics fit together to make sense. The authors havetherefore created a series of biochemical concept maps to graphicallyillustrate relationships between ideas presented in a chapter, and toshow how the information can be grouped or organized. A concept mapis thus a tool for visualizing the connections between concepts. Materialis represented in a hierarchical fashion with the most inclusive, mostgeneral concepts at the top of the map, and the more specific, less gen-eral concepts arranged beneath.

A. How is a concept map constructed?

1. Concept boxes and links: Educators define concepts as per-ceived regularities in events or objects. In our biochemical maps,concepts include abstractions (for example, free energy), pro-cesses (for example, oxidative phosphorylation), and compounds(for example, glucose 6-phosphate). These broadly defined con-cepts are prioritized with the central idea positioned at the top ofthe page. The concepts that follow from this central idea are then

→←

→←

IV. Concept Maps 9

Figure 1.12The Henderson-Hasselbalch equation is used to predict: A, changes in pH as the concentrations of HCO 3

– or CO 2 are altered;

H2CO3 HCO3-H+H2OCO2 + +

BICARBONATE AS A BUFFER

An increase in bicarbonate ion causes the pH to rise.

Pulmonary obstruction causes an increase in carbon dioxide and causes the pH to fall.

pH = pK + log [HCO3±]

[H2CO3]

DRUG ABSORPTION

At the pH of the stomach (1.5) a drug like aspirin (weak acid, pK = 3.5) will be largely protonated (COOH) and thus uncharged.

Uncharged drugs generally cross membranes more rapidly than charged molecules.

pH = pK + log [Drug-H] [Drug-]

A

B

A

HA

-

Lipidmembrane

LUMEN OF STOMACH

BLOOD

H+

H+

H+

A

HA

-H+

drawn in boxes (Figure 1.13A). The size of the box and type indi-cate the relative importance of each idea. Lines are drawnbetween concept boxes to show which are related. The label onthe line defines the relationship between two concepts, so that itreads as a valid statement, that is, the connection creates mean-ing. The lines with arrow heads indicate which direction the con-nection should be read.

2 Cross-links: Unlike linear flow charts or outlines, concept mapsmay contain cross-links that allow the reader to visualize complexrelationships between ideas represented in different parts of themap (Figure 1.13B), or between the map and other chapters inthis book, or companion books in the series (Figure 1.13C).Cross-links can thus identify concepts that are central to morethan one discipline, empowering students to be effective in clinicalsituations (and on USMLE or other examinations) that bridge dis-ciplinary boundaries. Students learn to visually perceive non-lin-ear relationships between facts, in contrast to cross referencingwithin linear text. .

B. Concept maps and meaningful learning

“Meaningful learning” refers to a process in which students link newinformation to relevant concepts that they already possess. In orderto learn meaningfully, individuals must consciously choose to relatenew information to knowledge that they already know, rather thansimply memorizing isolated facts or concept definitions. Rote isundesirable because such learning is easily forgotten, and is notreadily applied in new problem-solving situations. Thus, the conceptmaps prepared by the authors should not be memorized. This wouldmerely promote rote learning and so defeat the purpose of themaps. Rather, the concept maps ideally function as templates orguides for organizing the information, so the student can readily findthe best ways to integrate new information into knowledge theyalready possess.

V. CONCEPT SUMMARY

Each amino acid has a carboxyl group, and and amino group (exceptfor proline which has an imino group, Figure 1.14). At physiologic pH,the α-carboxyl group is dissociated, forming the negatively charged car-boxylate ion (–COO– ), and the α-amino group is protonated (– NH3

+).Each amino acid also contains one of twenty distinctive side chainsattached to the α-carbon atom. The chemical nature of this side chaindetermines the function of an amino acid in a protein, and provides thebasis for classification of the amino acids as nonpolar, uncharged polar,acidic, or basic. All free amino acids, plus charged amino acids in pep-tide chains, can serve as buffers. The quantitative relationship betweenthe concentration of a weak acid (HA) and its conjugate base (A–) isdescribed by the Henderson-Hasselbalch equation. Buffering occurswithin ± 1 pH unit of the pKa, and is maximal when pH = pKa where [A–]= [HA]. The α-carbon of each amino acid (except glycine) is attached tofour different chemical groups, and is therefore a chiral or opticallyactive carbon atom. Only the L-form of amino acids is found in proteinssynthesized by the human body.

10 1. Amino Acids

Figure 1.13Symbols used in concept maps.

Amino acids (fully protonated)

Release H+

can

A

B

Linked concept boxes

Microbiology

Lippincott's Illustrated Reviews

Protein turnover

Simultaneous synthesis and degradation

Degradation of body protein

Synthesis of body protein

is produced by

is consumed by

Amino acid pool

Amino acid pool

leads to

Concepts cross-linked within a map

C Concepts cross-linked to other chapters and to other books in the Lippincott Series

. . . how the protein folds into its native conformation

. . . how altered protein folding leads to prion disease such as Creutzfeldt- Jakob disease

see p. 397

V. Concept Summary 11

Figure 1.14Key concept map for protein structure.

α-Carboxyl group(–COOH)

α- Amino group(–NH3+)

Side chains of 20 different types

deprotonated (COO–) at physiologic pH

On the outside of proteins that function in an aqueous environment, and in the interior of membrane-associated proteins.

in the interior of proteins that functionin an aqueous environment, and on the surface of proteins (such as membrane proteins) that interact with lipids

Weak acids

Release H+

pH = pKa when [HA] = [A–]

Buffering occurs ± 1 pH unit of pKa

Buffering capacity

Maximal buffer when pH = pKa

protonated (NH3+ )

at physiologic pH

described by

composed of

and act asis is

are onlyOptically activeD and L forms

L-Amino acids are found in proteins

In proteins most α-COO– and α-NH3

+ of amino acids are combined in peptide bonds.

Therefore, thesegroups are not available forchemical reaction.

Thus, the chemical nature of the side chain determines the role that the amino acid plays in a protein,particularly . . .

. . . how theprotein foldsinto its nativeconformation.

Nonpolar side chains

AlanineGlycineIsoleucineLeucineMethioninePhenylalanineProlineTryptophanValine

Uncharged polar side chains

AsparagineCysteineGlutamineSerineThreonineTyrosine

Henderson-Hasselbalch equation:pH = pKa + log A–

HA

Amino acids(fully protonated)

Side chain dissociatesto –COO–at physiologic pH

Side chain is pro-tonated, and generally has a positive chargeat physiologic pH

characterized by characterized by

found found found found

predicts

predicts

predicts

predicts

are composed of can

Acidic side chains

Aspartic acidGlutamic acid

Basic side chains

ArginineHistidineLysine

12 1. Amino Acids

Study Questions

Choose the ONE best answer

1.1 Which one of the following correctly pairs an aminoacid with a valid chemical characteristic?

A. Glutamine: Contains a hydroxyl group in its side chain

B. Serine: Can form disulfide bonds

C. Cysteine: Contains the smallest side chain

D. Isoleucine: Is nearly always found buried in the center of proteins

E. Glycine: Contains an amide group in its side chain

1.2 Which one of the following statements concerning glu-tamine is correct?

A. Contains three titratable groups

B. Is classified as an acidic amino acid

C. Contains an amide group

D. Has E as its one-letter symbol

E. Migrates to the cathode (negative electrode) duringelectrophoresis at pH 7.0

Correct answer = D. In proteins found in aqueoussolutions, the side chains of the nonpolar aminoacids, such isoleucine, tend to cluster together inthe interior of the protein. Glutamine contains anamide in its side chain. Serine and threoninecontains a hydroxyl group in their side chain.Cysteine can form disulfide bonds. Glycinecontains the smallest side chain.

Correct answer = C. Glutamine contains two titrat-able groups, α-carboxyl and α-amino. Glutamineis a polar, neutral amino acid that shows littleelectrophoretic migration at pH 7.0. The symbolfor glutamine is “Q.”

Think about the question with a card covering the answer . . .

. . .then remove the card and confirm that your answer and reasoning are correct.

For the study questions, may we suggest...

1

2

1.1 Which one of the following correctly pairs an amino acid with a valid chemical characteristic?

A. Glutamine: Contains a hydroxyl group in its side chain B. Serine: Can form disulfide bonds C. Cysteine: Contains the smallest side chain D. Isoleucine: Is nearly always found buried in the center of proteins E. Glycine: Contains an amide group in its side chain

1.1 Which one of the following correctly pairs an amino acid with a valid chemical characteristic?

A. Glutamine: Contains a hydroxyl group in its side chain B. Serine: Can form disulfide bonds C. Cysteine: Contains the smallest side chain D. Isoleucine: Is nearly always found buried in the center of proteins E. Glycine: Contains an amide group in its side chain

Correct answer = D. In proteins found in aqueous solutions, the side chains of the nonpolar amino acids, such isoleucine, tend to cluster together in the interior of the protein. Glutamine contains an amide in its side chaine. Serine and threonine contains a hydroxyl group in their side chain. Cysteine can form disulfide bonds. Glycine contains the smallest side chain.