protein structure and function amino acids...

Amino Acids 1I. OVERVIEW

Proteins are the most abundant and functionally diverse molecules inliving 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 steelcables in reinforced concrete. In the bloodstream, proteins, such ashemoglobin and plasma albumin, shuttle molecules essential to life,whereas immuno globulins fight infectious bacteria and viruses. In short,proteins display an incredible diversity of functions, yet all share thecommon structural feature of being linear polymers of amino acids. Thischapter describes the properties of amino acids. Chapter 2 exploreshow these simple building blocks are joined to form proteins that haveunique three-dimensional structures, making them capable of perform-ing specific biologic functions.

II. STRUCTURE OF THE AMINO ACIDS

Although more than 300 different amino acids have been described innature, only 20 are commonly found as constituents of mammalian pro-teins. [Note: These are the only amino acids that are coded for by DNA,the genetic material in the cell (see p. 395).] Each amino acid (exceptfor proline, which has a secondary amino group) has a carboxyl group,a primary amino group, and a distinctive side chain (“R-group”) bondedto the α-carbon atom (Figure 1.1A). At physiologic pH (approximatelypH 7.4), the carboxyl group is dissociated, forming the negativelycharged carboxylate ion (–COO–), and the amino group is protonated(–NH3

+). In proteins, almost all of these carboxyl and amino groups arecombined through peptide linkage and, in general, are not available forchemical reaction except for hydrogen bond formation (Figure 1.1B).Thus, it is the nature of the side chains that ultimately dictates the role

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

C+H3N

NH-CH-CO-

COOH

HC+H3N

COC OH

H

Common to all α-amino acids of proteins

Free amino acid

Amino acids combinedthrough peptide linkages

R

R

NH-CH-CO

R

Aminogroup

Carboxylgroup

αC H

Carboxylgroup

α

RRAminogroup

R

Side chain is distinctive for each amino acid.

α-Carbon isbetween the carboxyl and the amino groups.

R R

Side chains determine properties of proteins.

A

B

1

UNIT I:Protein Structure

and Function

168397_P001-012.qxd7.0:02 Protein structure 5-20-04 2010.4.4 9:45 AM

an amino acid plays in a protein. It is, therefore, useful to classify theamino acids according to the properties of their side chains, that is,whether they are nonpolar (have an even distribution of electrons) orpolar (have an uneven distribution of electrons, such as acids andbases; 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 notgain or lose protons or participate in hydrogen or ionic bonds(Figure 1.2). The side chains of these amino acids can be thought ofas “oily” or lipid-like, a property that promotes hydro phobic inter -actions (see Figure 2.10, p. 19).

1. Location of nonpolar amino acids in proteins: In proteins found inaqueous solutions––a polar environment––the side chains of thenonpolar amino acids tend to cluster together in the interior of theprotein (Figure 1.4). This phenomenon, known as the hydrophobic

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 20 amino acids commonly found in proteins, according to the charge and polarity of their side chains at acidic pH 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 red print. The pK values for the α-carboxyl and α-amino groups of the nonpolar amino acids are similar to those shown for glycine. (Continued in Figure 1.3.)

C+H3N

COOH

H

CHCH3H3C

C+H3N

COOH

H

CH2

Leucine

CHCH3H3C

C+H3N

COOH

H

CH3

CH CH3

CH2

Isoleucine

2 1. Amino Acids


C+H3N

COOH

H

CH2

OHO

CH2

C

ACIDIC SIDE CHAINS

pK1 = 2.1

pK2 = 4.3

pK3 = 9.7C+H3N

COOH

CH2

Aspartic acid

OHOC

pK2 = 3.9

pK3 = 9.8

C+H3N

CH2

CH2

BASIC SIDE CHAINS

C+H3N

CH2

pK3 = 9.2

CH

NHCH

+HN

C

pK2 = 6.0

CH2

CH2

NH3+ pK3 = 10.5

C+H3N

CH2

CH2

CH2

N

pK3 = 12.5

H

C

NH2

NH2+

C+H3N H

CH2

NH2O

C+H3N

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

COOHH

Serine

C

H

H OH

C+H3N

Threonine

C

CH3

H OH

C+H3N

COOHH

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

NH2O

CH2

C

UNCHARGED POLAR SIDE CHAINS

CH2

C

C OH

C+H3N

COOHH

C

CH3

H OH

+H3N

Tyrosine

pK3 = 10.1

C

Figure 1.3Classification of the 20 amino acids commonly found in proteins, according to the charge and polarity of their side chains at acidic pH (continued from Figure 1.2).

pK2 = 9.2

II. Structure of the Amino Acids 3


effect, is the result of the hydro phobicity of the nonpolar R-groups,which act much like droplets of oil that coalesce in an aqueousenvironment. The nonpolar R-groups thus fill up the interior of thefolded protein and help give it its three-dimensional shape.However, for proteins that are located in a hydrophobic environ-ment, such as a membrane, the nonpolar R-groups are found onthe outside surface of the protein, interacting with the lipid envi-ronment (see Figure 1.4). The importance of these hydrophobicinteractions in stabilizing protein structure is discussed on p. 19.

Sickle cell anemia, a sickling disease of redblood cells, results from the substitution of polarglutamate by nonpolar valine at the sixth positionin the β subunit of hemoglobin (see p. 36).

2. Proline: Proline differs from other amino acids in that proline’sside chain and α-amino N form a rigid, five-membered ring struc-ture (Figure 1.5). Proline, then, has a secondary (rather than a pri-mary) amino group. It is frequently referred to as an imino acid.The unique geometry of proline contributes to the formation of thefibrous structure of collagen (see p. 45), and often interrupts theα-helices found in globular proteins (see p. 26).

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 formation(Figure 1.6). The side chains of asparagine and glutamine eachcontain a carbonyl group and an amide group, both of which canalso participate in hydrogen bonds.

1. Disulfide bond: The side chain of cysteine contains a sulf hydrylgroup (–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. 19 fora further discussion of disulfide bond formation.)

Many extracellular proteins are stabilized bydisulfide bonds. Albumin, a blood protein thatfunctions as a transpor ter for a var iety ofmolecules, is an example.

2. Side chains as sites of attachment for other compounds: Thepolar hydroxyl group of serine, threonine, and, rarely, tyrosine, canserve as a site of attachment for structures such as a phosphategroup. In addition, the amide group of asparagine, as well as thehydroxyl group of serine or threonine, can serve as a site of attach-ment for oligosaccharide chains in glycoproteins (see p. 165).

Figure 1.6Hydrogen bond between thephenolic hydroxyl group of tyrosine and another molecule containing acarbonyl group.

C+H3N

COOH

CH2

Tyrosine

Hydrogenbond

O

C

O

H

H

Carbonylgroup

4 1. Amino Acids

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

Cellmembrane

Polar amino acids( ) cluster onthe surface of soluble proteins.

Cell

Nonpolar aminoacids ( ) cluster on the surface of membrane proteins.

Nonpolar amino acids ( ) cluster in the interior of soluble proteins.

Soluble protein Membrane protein

Figure 1.5Comparison of the secondary amino group found in proline with the primary amino group found in other amino acids, such as alanine.

C+H3N

COOH

H

CH3

Alanine

COOH

H

Proline

C

CH2

+H2N

H2C

Primary aminogroup

Secondary aminogroup

CH2


C. Amino acids with acidic side chains

The amino acids aspartic and glutamic acid are proton donors. Atphysiologic pH, the side chains of these amino acids are fully ionized,containing a negatively charged carboxylate group (–COO–). They are,therefore, 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,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. Thisis an important property of histidine that contributes to the role itplays in the functioning of proteins such as hemoglobin (see p. 31).

E. Abbreviations and symbols for 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 are deter-mined 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 letter of the amino acid, for example, K = lysine.Furthermore, B is assigned to Asx, signifying either aspartic acidor asparagine, Z is assigned to Glx, signifying either glutamic acidor glutamine, and X is assigned to an unidentified amino acid.

F. Optical properties of amino acids

The α-carbon of an amino acid is attached to four different chemicalgroups 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. Amino acids thathave an asymmetric center at the α-carbon can exist in two forms,designated D and L, that are mirror images of each other (Figure1.8). The two forms in each pair are termed stereoisomers, opticalisomers, or enantiomers. All amino acids found in proteins are of theL-configuration. However, D-amino acids are found in some antibi-otics and in plant and bacterial cell walls. (See p. 253 for a discus-sion of D-amino acid metabolism.)

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) asparagineGlutamate or = Glx = Z glutamineLysine = Lys = K (near L)Undetermined = X amino acid

Unique first letter:

Most commonly occurring amino acids have priority:

Similar sounding 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

II. Structure of the Amino Acids 5


III. ACIDIC AND BASIC 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 inpeptide linkages can act as buffers. Recall that acids may be defined asproton donors and bases as proton acceptors. Acids (or bases)described as “weak” ionize to only a limited extent. The concentration ofprotons in aqueous solution is expressed as pH, where pH = log 1/[H+]or –log [H+]. The quantitative relationship between the pH of the solu-tion and concentration of a weak acid (HA) and its con jugate base (A–)is described 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 weak acid.By definition, the dissociation constant of the acid, Ka, is

[Note: The larger the Ka, the stronger the acid, because most of theHA has dissociated into H+ and A–. Conversely, the smaller the Ka,the less acid has dissociated and, therefore, the weaker the acid.]By solving for the [H+] in the above equation, taking the logarithm ofboth sides of the equation, multiplying both sides of the equation by–1, and substituting pH = – log [H+ ] and pKa = – log Ka, we obtainthe Henderson-Hasselbalch equation:

B. Buffers

A buffer is a solution that resists change in pH following the addition ofan acid or base. A buffer can be created by mixing a weak acid (HA) withits conjugate base (A–). If an acid such as HCl is then added to such asolution, A– can neutralize it, in the process being converted to HA. If abase is added, HA can neutralize it, in the process being converted toA–. Maximum buffering capacity occurs at a pH equal to the pKa, but aconjugate acid/base pair can still serve as an effective buffer when thepH of a solution is within approximately ±1 pH unit of the pKa. If the

6 1. Amino Acids

Figure 1.9Titration curve of acetic acid.

0 3 4 5 6 70

0.5

1.0

pH

Eq

uiv

alen

ts O

H– a

dd

ed

Buffer region

CH3COOH CH3COO–

H20

FORM I(acetic acid, HA)

FORM II(acetate, A–)

pKa = 4.8[I] = [II]

OH–

H+

[I] > [II]

[II] > [I]

pH pKa log[A–][HA]

+

Ka[A–]

[HA][H+]


amounts of HA and A– are equal, the pH is equal to the pKa. As shown inFigure 1.9, a solution containing acetic acid (HA = CH3 –COOH) andacetate (A– = CH3 –COO–) with a pKa of 4.8 resists a change in pH frompH 3.8 to 5.8, with maximum buffering at pH 4.8. At pH values less thanthe pKa, the protonated acid form (CH3 – COOH) is the predominantspecies. At pH values greater than the pKa, the deprotonated base form(CH3 – COO–) is the predominant species in solution.

C. Titration of an amino acid

1. Dissociation of the carboxyl group: The titration curve of anamino acid can be analyzed in the same way as described foracetic acid. Consider alanine, for example, which contains bothan α-carboxyl and an α-amino group. At a low (acidic) pH, both ofthese groups are proton ated (shown in Figure 1.10). As the pH ofthe solution is raised, the – COOH group of Form I can dissociateby donating a proton to the medium. The release of a protonresults in the formation of the carboxylate group, – COO–. Thisstructure is shown as Form II, which is the dipolar form of themolecule (see Figure 1.10). This form, also called a zwitterion, isthe isoelectric form of alanine, that is, it has an overall (net)charge of zero.

2. Application of the Henderson-Hasselbalch equation: The dissoci-ation constant of the carboxyl group of an amino acid is called K1,rather than Ka, because the molecule contains a second titratablegroup. The Henderson-Hasselbalch equation can be used to analyze the dissociation of the carboxyl group of alanine in thesame way as described for acetic acid:

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

III. Acidic and Basic Properties of Amino Acids 7

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

COOH

FORM I

Alanine in acid solution(pH less than 2)

Net charge = +1

CH3

C+H3N HCOO–

FORM II

Alanine in neutral solution(pH approximately 6)

Net charge = 0(isoelectric form)

CH3

C+H3N HCOO–

FORM III

Alanine in basic solution(pH greater than 10)

Net charge = –1

CH3

CH2N H

H20OH–

H+

H20OH–

H+

pK1 = 2.3 pK2 = 9.1

K1[II]

[I][H+]


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 thereforelarger.] 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 titratable group has a pKa that is numer ically equal tothe pH at which exactly one half of the protons have beenremoved from that group. The pKa for the most acidic group(–COOH) is pK1, whereas the pKa for the next most acidic group(– NH3

+) is pK2.

5. Titration curve of alanine: By applying the Hender son-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 thecompletely 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. Whenthe pH is equal to pK2 (9.1), equal amounts of Forms II and IIIare present 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, thatis, in which the sum of the positive charges equals the sum ofthe negative charges. For an amino acid, such as alanine, thathas only two dissociable hydrogens (one from the α-carboxyland one from the α-amino group), the pI is the average of pK1

and pK2 (pI = [2.3 + 9.1]/2 = 5.7, see Figure 1.11). The pI isthus midway between pK1 (2.3) and pK2 (9.1). pI correspondsto the pH at which the Form II (with a net charge of zero) pre-dominates, and at which there are also equal amounts ofForms I (net charge of +1) and III (net charge of –1).

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

ts O

H– a

dd

ed

pK2 = 9.1

[II] = [III]

0.5

1.5

pK1 = 2.3

[I] = [II]

pI = 5.7

Region of buffering

Region of buffering

0 2 40

p

[II] = [III]

Region of buffering

6 8 10pH

ppK2 = 9.=

= 2.3

p

COOH

FORM I

CH3

C+H3N H

COO–

FORM III

CH3

CH2N H

COO–

FORM II

CH3

C+H3N H

pH pK1 log[II][I]

+


Separation of plasma proteins by charge typicallyis done at a pH above the pI of the major pro-teins, thus, the charge on the proteins is negative.In an electric field, the proteins will move towardthe positive electrode at a rate determined bytheir net negative charge. Variations in the mobil-ity pattern are suggestive of certain diseases.

6. Net charge of amino acids at neutral pH: At physiologic pH,amino 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 acidor a 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-tration of a weak acid and/or its corresponding “salt” form. For exam-ple, in the bicarbonate buffer system, the Henderson-Hasselbalchequation predicts how shifts in the bicarbonate ion concentration,[HCO3

–], and CO2 influence pH (Figure 1.12A). The equation is alsouseful for calculating the abundance of ionic forms of acidic andbasic drugs. For example, most drugs are either weak acids or weakbases (Figure 1.12B). Acidic drugs (HA) release a proton (H+), caus-ing 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 the 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 such as aspirin, the uncharged HA can per-meate through membranes and A– cannot. For a weak base, suchas morphine, the uncharged form, B, penetrates through the cellmembrane and BH+ does not. Therefore, the effective concentrationof the permeable form of each drug at its absorption site is deter-mined by the relative concentrations of the charged and unchargedforms. The ratio between the two forms is determined by the pH atthe site of absorption, and by the strength of the weak acid or base,which is represented by the pKa of the ionizable group. TheHenderson-Hasselbalch equation is useful in determining how muchdrug is found on either side of a membrane that separates two com-partments that differ in pH, for example, the stomach (pH 1.0–1.5)and blood plasma (pH 7.4).

→←

→←

Figure 1.12The Henderson-Hasselbalch equation is used to predict: A, changes in pH as the concentrations of HCO3

– or CO2 are altered; or B, the ionic forms of drugs.

H2CO3 HCO3-H+H2OCO2 + +

BICARBONATE AS A BUFFER

An increase in HCO3–

causes the pH to rise.

Pulmonary obstruction causes an increase in carbon dioxide and causes the pH to fall, resultingin respiratory acidosis.

pH = pK + log [HCO3– ]

[CO2]

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

STOMACH

LUNGALVEOLI

BLOOD

H+

H+

H+

A

HA

-H+

III. Acidic and Basic Properties of Amino Acids 9


IV. CONCEPT MAPS

Students sometimes view biochemistry as a blur of facts or equations tobe memorized, rather than a body of concepts to be understood. Detailsprovided to enrich understanding of these concepts inadvertently turninto distractions. What seems to be missing is a road map—a guide thatprovides the student with an intuitive understanding of how various top-ics fit together to make sense. The authors have, therefore, created aseries of biochemical concept maps to graphically illustrate relationshipsbetween ideas presented in a chapter, and to show how the informationcan be grouped or organized. A concept map is, thus, a tool for visualiz-ing the connections between concepts. Material is represented in a hier-archic fashion, with the most inclusive, most general concepts at the topof the map, and the more specific, less general concepts arrangedbeneath. The concept maps ideally function as templates or guides fororganizing information, so the student can readily find the best ways tointegrate new information into knowledge they already possess.

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 thendrawn in boxes (Figure 1.13A). The size of the type indicates therelative importance of each idea. Lines are drawn between con-cept boxes to show which are related. The label on the linedefines the relationship between two concepts, so that it reads asa valid statement, that is, the connection creates meaning. Thelines with arrowheads indicate in which direction the connectionshould be read (Figure 1.14).

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 more than onediscipline, empowering students to be effective in clinical situa-tions, and on the United States Medical Licensure Exam ination(USMLE) or other examinations, that bridge disciplinary bound-aries. Students learn to visually perceive nonlinear relationshipsbetween facts, in contrast to cross-referencing within linear text.

V. CHAPTER SUMMARY

Each amino acid has an α-carboxyl group and a primary α-aminogroup (except for proline, which has a secondary amino group). Atphysiologic pH, the α-carboxyl group is dissociated, forming the nega-tively charged carboxylate ion (– COO–), and the α-amino group is pro-tonated (– NH3

+). Each amino acid also contains one of 20 distinctive

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 IllustratedReviews

Protein turnover

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 andto other books in theLippincott Series

. . . how theprotein foldsinto its nativeconformation

. . . how alteredprotein foldingleads to priondisease, suchas Creutzfeldt-Jakob disease

Simultaneous synthesis and degradation

Structureof Proteins 2


V. Chapter Summary 11

Figure 1.14Key concept map for amino acids.

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

grouped as

and act asis is

In proteins, most α-COO– and α-NH3

+ of amino acids are combined through 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 . . .

Nonpolar side chains

AlanineGlycineIsoleucineLeucineMethioninePhenylalanineProlineTryptophanValine

Uncharged polar side chains

AsparagineCysteineGlutamineSerineThreonineTyrosine

Henderson-Hasselbalch equation:

[A–][HA]

Amino acids

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

Acidic side chains

Aspartic acidGlutamic acid

Basic side chains

ArginineHistidineLysine

α-Carboxyl group(–COOH)

α-Amino group(–NH2)

Side chains (20 different ones)

are composed of when protonated can

. . . how theprotein foldsinto its nativeconformation.

Structureof Proteins 2

pH = pKa + log


Correct answer = C. C represents the isoelectricpoint or pI, and as such is midway between pK1

and pK2 for this monoamino monocarboxylicacid. Glycine is fully protonated at Point A. PointB represents a region of maximum buffering, asdoes Point D. Point E represents the regionwhere glycine is fully deprotonated.

Correct answer = D. The two cysteine residuescan, under oxidizing conditions, form a disulfidebond. Glutamine’s 3-letter abbreviation is Gln.Proline (Pro) contains a secondary amino group.Only one (Arg) of the seven would have a posi-tively charged side chain at pH 7.

Correct answer = negative electrode. When thepH is less than the pI, the charge on glycine ispositive because the α-amino group is fully pro-tonated. (Recall that glycine has H as its Rgroup).

12 1. Amino Acids

side chains attached to the α-carbon atom. The chemical nature of this side chain determines the function ofan amino acid in a protein, and provides the basis for classification of the amino acids as nonpolar,uncharged polar, acidic, or basic. All free amino acids, plus charged amino acids in peptide chains, can serveas buffers. The quantitative relationship between the pH of a solution and the concentration of a weak acid(HA) and its con jugate base (A–) is described by the Henderson-Hasselbalch equation. Buffering occurswithin ±1pH unit of the pKa, and is maximal when pH = pKa, at which [A–] = [HA]. The α-carbon of each aminoacid (except glycine) is attached to four different chemical groups and is, therefore, a chiral or optically activecarbon atom. Only the L-form of amino acids is found in proteins synthesized by the human body.

Study Questions

Choose the ONE correct answer.

1.1 The letters A through E designate certain regions onthe titration curve for glycine (shown below). Whichone of the following statements concerning this curveis correct?

A. Point A represents the region where glycine isdeprotonated.

B. Point B represents a region of minimal buffering.C. Point C represents the region where the net charge

on glycine is zero.D. Point D represents the pK of glycine’s carboxyl

group.E. Point E represents the pI for glycine.

1.2 Which one of the following statements concerning thepeptide shown below is correct?

Gly-Cys-Glu-Ser-Asp-Arg-CysA. The peptide contains glutamine.B. The peptide contains a side chain with a secondary

amino group.C. The peptide contains a majority of amino acids with

side chains that would be positively charged at pH 7.D. The peptide is able to form an internal disulfide

bond.

1.3 Given that the pI for glycine is 6.1, to which electrode,positive or negative, will glycine move in an electricfield at pH 2? Explain.

0 2 4 6 8 100

1.0

2.0

pH

Eq

uiv

alen

ts O

H– a

dd

ed

0.5

1.5

A

B

C

D

E


protein structure and function amino acids...

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