ch2

© 2013 Pearson Education, Inc.

Molecular Interactions

Chapter 2

Biomolecules

• Organic molecules contain carbon– Biomolecules are associated with living organisms

– Carbohydrates– Lipids– Proteins– Nucleotides– Conjugated proteins: combined biomolecules (e.g.,

lipoproteins; blood transport molecules)– Glycosylated molecules: carbohydrates are attached (e.g.,

glycoproteins, glycolipids) in cell membranes– Polymers, large molecules made of repeating unit


Figure 2.1-1 REVIEW – Biochemistry of Lipids

Fatty Acids

Fatty acids are long chains of carbon atoms bound to hydrogens,with a carbon (–COOH) or “acid” group at one end of the chain.

Saturated fatty acids have no double bonds between carbons, sothey are “saturated” with hydrogens. The more saturated a fatty acidis, the more likely it is to be solid at room temperature.

Palmitic acid, a saturated fatty acid

Linolenic acid, a polyunsaturated fatty acid

Oleic acid, a monounsaturated fatty acid

Polyunsaturated fatty acids have two or more double bonds between carbons in the chain.

Monounsaturated fatty acids have one double bond between twoof the carbons in the chain. For each double bond, the moleculehas two fewer hydrogen atoms attached to the carbon chain.

Figure 2.1-3 REVIEW – Biochemistry of Lipids

Lipid-Related Molecules

Steroids are lipid-related moleculeswhose structureincludes fourlinked carbonrings.

SteroidsEicosanoids

In addition to true lipids, this category includes three types of lipid-related molecules.

Eicosanoids {eikosi, twenty} aremodified 20-carbon fatty acids with acomplete or partial carbon ring atone end and two long carbon chain“tails.”

Phospholipids have 2 fatty acidsand a phosphate group (–H2PO4).Cholesterol and phospholipids areimportant compounds of animalcell membranes.

Phospholipids

Prostaglandin E2 (PGE2)

Eicosanoids, such as thromboxanes,leukotrienes, and prostaglandins, actas regulators of physiologicalfunctions.

Cortisol

Cholesterol is the primary sourceof steroids in the human body. Fatty acid

Fatty acid

GLYCEROL

Phosphate group

P

Figure 2.2-1 REVIEW – Biochemistry of Carbohydrates

Monosaccharides

Five Carbon Sugars (Pentoses)

Forms the sugar-phosphatebackbone of RNA

Forms the sugar-phosphate backbone of RNA

Notice that the only differencebetween glucoseand galactose isthe spatialarrangement ofthe hydroxyl(–OH) groups.

Six Carbon Sugars (Hexoses)

Monosaccharides are simple sugars. The most common monosaccharides are the building blocksof complex carbohydrates and have either five carbons, like ribose, or six carbons, like glucose.

Ribose Deoxyribose Glucose (dextrose)Fructose Galactose

Carbohydrates


Disaccharides

Disaccharides consist of glucoseplus another monosaccharide. Sucrose (table sugar)

*In shorthand chemical notation,the carbons in the rings andtheir associated hydrogenatoms are not written out.Compare this notation to theglucose structure in the rowabove.

Maltose

Glucose* + Fructose Glucose + Glucose

Lactose

Galactose + Glucose


Polysaccharides

Polysaccharides are glucosepolymers. All living cells storeglucose for energy in the formof a polysaccharide.

** Chitin and cellulose are structural polysaccharides.

Chitin** Glycogen

Animals

in invertebrateanimals

Glucosemolecules

Digestion of starchor glycogen yields

maltose.

Cellulose**Humans cannotdigest celluloseand obtain itsenergy, even

though it is themost abundantpolysaccharide

on earth.

Plants

Starch

Yeastsand bacteria

Dextran

Figure 2.3-1 REVIEW – Biochemistry of Proteins

Amino Acids

The R groups differ in their size, shape,and ability to form hydrogen bonds orions. Because of the different R groups,each amino acid reacts with othermolecules in a unique way.

The nitrogen (N) in the amino groupmakes proteins our major dietarysource of nitrogen.

All amino acids have a carboxyl group (–COOH), an amino group(–NH2), and a hydrogen attached to the same carbon. The fourthbond of the carbon attaches to a variable “R” group.


Amino Acids in Natural Proteins

A few amino acids do not occur in proteins but have importantphysiological functions.

Twenty different amino acids commonly occur in naturalproteins. The human body can synthesize most of them, but atdifferent stages of life some amino acids must be obtainedfrom diet and are therefore considered essential amino acids.

Amino AcidOne-LetterSymbol

Three-LetterAbbreviation

Asparagine

Alanine

Arginine

Asparagine or aspartic acid

Aspartic acid

Cysteine

Glycine

IsoleucineHistidine

Glutamine or glutamic acid

Glutamic acid

Glutamine

Leucine

Proline

Serine

Phenylalanine

LysineMethionine

Tyrosine

Valine

TryptophanThreonine

Gly

IleHis

Leu

Pro

Ser

Phe

LysMet

Tyr

Val

TrpThr

Asn

Ala

Arg

Asx

Asp

Cys

Glx

Glu

Gln

G

IH

L

P

S

F

KM

Y

V

WT

N

A

R

B

D

C

Z

E

Q

Note:

• Creatine: a molecule that stores energy when it binds to a phosphate group

• Homocysteine: a sulfur-containing amino acid that in excessis associated with heart disease

• γ-amino butyric acid (gamma-amino butyric acid) or GABA: a chemical made by nerve cells


Primary Structure

Structure of Peptides and Proteins

Sequence of amino acids

The 20 protein-forming amino acids assemble into polymerscalled peptides. The sequence of amino acids in a peptide chainis called the primary structure. Just as the 26 letters of our alphabet combine to create different words, the 20 amino acidscan create an almost infinite number of combinations.

Peptides range in length from two to two million amino acids:

• Proteins: >100 amino acids

• Polypeptide: 10–100 amino acids

• Oligopeptide {oligo-, few}: 2–9 amino acids

Molecular Shape and Function

• Molecular bonds determine shape– Shape is closely related to function

• Proteins have the most complex and varied shapes– Primary structure: amino acids, differ by functional group– Secondary structures: alpha-helix and beta-pleated sheets

– Chains like structures– Tertiary structure

– Chains fold– Quaternary Structure

– Disulfide bonds (S-S)– multiple subunits/proteins combine– binding sites


Figure 2.4-2 REVIEW – Nucleotides and Nucleic Acids

A nucleotide consists of (1) one or more phosphategroups, (2) a 5-carbon sugar, and (3) a carbon-nitrogenring structure called anitrogenous base.

Nucleotide

Base

Sugar

Phosphate


Nitrogenous Base

Pyrimidines have a single ring.

Purines have a double ring structure.

Adenine (A) Guanine (G) Cytosine (C) Thymine (T) Uracil (U)


Deoxyribose{de-, without: oxy-, oxygen}

5-carbon Sugar

Ribose


Phosphate


Nucleotide

Single Nucleotide Molecules

Base Sugar Phosphate Groupsconsists of Other Component+ + + Function

Cell-to-cell communication

Energy capture and transfer

ATP

ADP

NAD

= Adenine Ribose 3 phosphate groups

Adenine Ribose 2 phosphate groups

Adenine 2 Ribose 2 phosphate groups Nicotinamide

Adenine

+

+

+

+ FAD

cAMP Adenine

=

=

=

= +

Ribose

Ribose

+

+

+

+

+

2 phosphate groups Riboflavin +

+

Molecules and Bonds

• Bonds link atoms• Bonds store and transfer energy• Molecules versus weaker interactions


Isotopes and Ions

An atom that gains orloses neutrons becomes anisotope of the same element.

An atom that gains or loses electrons becomes an ion of the same element.

1H, Hydrogen

2H, Hydrogen isotope

H+, Hydrogen ion

gains aneutron

loses anelectron

Figure 2.5-2 REVIEW – Atoms and Molecules

Four Important Roles of Electrons

• Covalent bonds• Ions• High-energy electrons• Free radicals


Table 2. 2 Important Ions of the Body

Types of Chemical Bonds – Covalent Bonds

• Covalent bonds– Share a pair of electrons– Single, double, and triple bonds– Polar covalent vs nonpolar covalent molecules– Ex of Covalent bonds: CO2, H2O, CH4, NH3


Figure 2.6a-b REVIEW – Molecular Bonds

Covalent Bonds

Nonpolar Molecules

Polar Molecules

Covalent bonds result when atoms share electrons.These bonds require the most energy to make or break.

Nonpolar molecules have an evendistribution of electrons. Forexample, molecules composedmostly of carbon and hydrogen tendto be nonpolar.

Polar molecules have regions ofpartial charge (δ+ or δ -). The mostimportant example of a polarmolecule is water.

δ+ δ+

δ -δ -

Fatty acidHydrogen

Carbon

Negative pole

Positive pole

Water molecule

Ions

• Ions are charged atoms – Cations

– Lost electrons– Positively charged (+)

– Anions – Gained electrons– Negatively charged (−)


Types of Chemical Bonds – Ionic Bonds

• Ionic bonds– Atoms gain or lose electrons– Opposite charges attract– Ex of ionic bonds: NaCl, KCl, CaCl2, NaF


Figure 2.6c REVIEW – Molecular Bonds

Noncovalent Bonds

Ionic Bonds

Na NaCl Cl

−+

Sodium atom Chlorine atomSodium ion (Na+)

Chloride ion (Cl−)

Ionic bonds are electrostatic attractions between ions. A common example is sodium chloride.

Sodium gives up its one weakly heldelectron to chlorine, creating sodium andchloride ions, Na+ and Cl−.

The sodium and chloride ions both have stableouter shells that are filled with electrons. Becauseof their opposite charges, they are attracted toeach other and, in the solid state, the ionic bondsform a sodium chloride (NaCl) crystal.

Types of Chemical Bonds – Hydrogen and Van der Waals

• Hydrogen bonds– Weak and partial : btw H and nearby O, N, or F atom– Water properties: surface tension, capillary action, solutions– Important in DNA and proteins– broken by heat and extreme pH

• Van der Waals forces – Weak and nonspecific– Btw nucleus of one atom and electrons of another– occurs until electrons repel each other


Figure 2.6d REVIEW – Molecular Bonds

Hydrogen Bonds

Hydrogenbonding

Hydrogen bonds form betweena hydrogen atom and a nearbyoxygen, nitrogen, or fluorineatom. So, for example, thepolar regions of adjacentwater molecules allow themto form hydrogen bondswith one another. Hydrogen bonding

between water moleculesis responsible for thesurface tension of water.

Aqueous Solutions

• Aqueous– Water-based

• Solution– Solute dissolves in solvent

• Solubility– Ease of dissolving

– Hydrophilic– Hydrophobic


Figure 2.7-2 REVIEW – Solutions

TERMINOLOGY

Concentration = solute amount/volume of solution

A solute is any substance that dissolves in a liquid. The degree towhich a molecule is able to dissolve in a solvent is the molecule’s solubility. The more easily a solute dissolves, the higher itssolubility.

A solvent is the liquid into which solutes dissolve. In biologicalsolutions, water is the universal solvent.

A solution is the combination of solutes dissolved in a solvent. The concentration of a solution is the amount of solute per unitvolume of solution.


EXPRESSIONS OF SOLUTE AMOUNT

Example

• Mass (weight) of the solute before it dissolves. Usually given in grams (g) or milligrams (mg).

• Molecular mass is calculated from the chemical formula of a molecule. This is the mass of one molecule, expressed in atomic mass units (amu) or, more often, in daltons (Da), where 1 amu = 1 Da.

Molecular mass = SUM ×atomic massof each element

the number of atomsof each element[ ]

What is themolecular massof glucose,C6H12O6? Carbon

Hydrogen

Oxygen 6

612

12.0 amu × 6 = 72

1.0 amu × 12 = 12

16.0 amu × 6 = 96

Molecular mass of glucose = 180 amu (or Da)

AnswerElement # of Atoms Atomic Mass of Element

• Moles (mol) are an expression of the number of solute molecules, without regard for their weight. One mole = 6.02 × 1023 atoms, ions, or molecules of a substance. One mole of a substance has the same number of particles as one mole of any other substance, just as a dozen eggs has the same number of items as a dozen roses.

• Gram molecular weight. In the laboratory, we use the molecular mass of a substance to measure out moles. For example, one mole of glucose (with 6.02 × 1023 glucose molecules) has a molecular mass of 180 Da and weighs 180 grams. The molecular mass of a substance expressed in grams is called the gram molecular weight.

• Equivalents (eq) are a unit used for ions, where 1 equivalent = molarity of the ion × the number of charges the ion carries. The sodium ion, with its charge of +1, has one equivalent per mole. The hydrogen phosphate ion (HPO4

2-) has two equivalents per mole. Concentrations of ions in the blood are often reported in milliquivalents per liter (meq/L).


EXPRESSIONS OF VOLUME

Volume is usually expressed as liters (L) or milliliters (mL)(milli-, 1/1000). A volume convention common in medicine isthe deciliter (dL), which is 1/10 of a liter, or 100 mL.

deci- (d)

milli- (m)

micro- (μ)

nana- (n)

pico- (p)

Prefixes

1/10

1/1000

1/1,000,000

1/1,000,000,000

1/1,000,000,000,000

1 × 10-1

1 × 10-3

1 × 10-6

1 × 10-9

1 × 10-12


EXPRESSIONS OF CONCENTRATION

Answer

Answer

Example

Example

• Percent solutions. In a laboratory or pharmacy, scientists cannot measure out solutes by the mole. Instead, they use the more conventional measurement of weight. The solute concentration may then be expressed as a percentage of the total solution, or percent solution. A 10% solution means 10 parts of a solute per 100 parts of total solution. Weight/volume solutions, used for solutes that are solids, are usually expressed as g/100 mL solution or mg/dL. An out-of-date way of expressing mg/dL is mg% where % means per 100 parts or 100 mL. A concentration of 20 mg/dL could also be expressed as 20mg%.

Solutions used forintravenous (IV)infusions are oftenexpressed aspercent solutions.How would youmake 500 mL of a5% dextrose(glucose) solution?

5% solution = 5 g glucose dissolved in water to make afinal volume of 100 mL solution.

5 g glucose/100 mL = ? g/500 mL

25 g glucose with water added to give a final volume of500 mL

• Molarity is the number of moles of solute in a liter of solution, and is abbreviated as either mol/L or M. A one molar solution of glucose (1 mol/L, 1 M) contains 6.02 × 1023 molecules of glucose per liter of solution. It is made by dissolving one mole (180 grams) of glucose in enough water to make one liter of solution. Typical biological solutions are so dilute that solute concentrations are usually expressed as millimoles per liter (mmol/l or mM).

What is themolarity of a5% dextrosesolution?

5 g glucose/100 mL = 50 g glucose/1000 mL (or 1 L)

1 mole glucose = 180 g glucose

50 g/L × 1 mole/180 g = 0.278 moles/L or 278 mM

Figure 2.8a REVIEW – Molecular Interactions

Hydrophilic Interactions

Molecules that have polarregions or ionic bondsreadily interact with the polarregions of water. This enablesthem to dissolve easily inwater. Molecules thatdissolve readily in water aresaid to be hydrophilic(hydro-, water + philos,loving).

Water molecules interact withions or other polar molecules toform hydration shells aroundthe ions. This disrupts thehydrogen bonding betweenwater molecules, therebylowering the freezing tempera-ture of water (freezing pointdepression).

NaCl in solution Glucose molecule in solution

Hydrationshells

Glucosemolecule

Watermolecules

Cl-

Na+

Figure 2.8b REVIEW – Molecular Interactions

Hydrophobic Interactions

Because they have an evendistribution of electrons andno positive or negative poles,nonpolar molecules have noregions of partial charge, andtherefore tend to repel watermolecules. Molecules likethese do not dissolve readilyin water and are said to behydrophobic (hydro-, water+ phobos, fear). Moleculessuch as phospholipids haveboth polar and nonpolarregions that play critical rolesin biological systems and inthe formation of biologicalmembranes.

Phospholipid molecules have polar heads and nonpolar tails. Phospholipids arrange themselves sothat the polar heads are in contact withwater and the nonpolar tails aredirected away from water.

This characteristic allows the phospho-lipid molecules to form bilayers, thebasis for biological membranes thatseparate compartments.

Water

Water

Hydrophilic head

Hydrophobic tails

Hydrophilic head

Polar head(hydrophilic)

Nonpolarfatty acid

tail(hydrophobic)

Molecular models Stylized model

Hydrogen Ion Concentration (pH)

• Free H+ can change a molecule’s shape (hydrogen bonds and van der Waals forces)

• pH– Measure of the concentration of free H+ – pH scale

• Acid– Contributes to H+ solution

• Buffer moderates changes in pH (bicarbonate, phosphate, protein)

• pH is important for proteins to function normally=sustainable for life 7.0-7.8; 7.4 ideally)


Figure 2.9-1 REVIEW – pH

ACIDS AND BASES

An acid is a molecule thatcontributes H+ to a solution.

A base is a molecule that decreases the H + concentration of a solution by combining with free H +.

• The carboxyl group, –COOH, is an acid because in solution it tends to lose its H+:

• Another molecule that acts as a base in ammonia, NH3. It reacts with a free H+ to form an ammonium ion:

• Molecules that produce hydroxide ions, OH−, in solution are bases because the hydroxide combines with H+ to form water:

Figure 2.9-2 REVIEW – pH

pH

The concentration of H+ in body fluids is measured in terms of pH.

• The expression pH stands for “power of hydrogen.”

This equation is read as “pH is equal to the negative log ofthe hydrogen ion concentration.” Square brackets areshorthand notation for “concentration” and by convention,concentration is expressed in meq/L.

• Using the rule of logarithms that says −log x = log(1/x), pH equation (1) can be rewritten as:

This equation shows that pH is inversely related to H+

concentration. In other words, as the H + concentrationgoes up, the pH goes down.

Example

What is the pH ofa solution whosehydrogen ionconcentration[H+] is 10-7

meq/L?

AnswerpH = −log [H+]pH = −log [10-7]

pH = log (1/10-7)

pH = log 107

Using the rule of logs,this can be rewritten as

Using the rule of exponentsthat says 1/10x = 10-x

the log of 107 is 7, sothe solution has a pH of 7.

Proteins

• Enzymes• Membrane transporters• Signal molecules• Receptors• Binding proteins• Immunoglobulins• Regulatory proteins


Protein Interactions

• Binding– Noncovalent bonds with other molecules– Occurs at binding site (specificity, affinity, competition,

saturation)– Go to a state of equilibrium

• Ligands: any molecule that binds to another molecule– Substrates

• Proteins are specific about bonding• Molecular complementarity

– Induced-fit model– Affinity


Figure 2.10 The induced-fit model of protein–ligand (L) binding

In this model of protein binding,the binding site shape is not an

exact match to the ligands’ (L) shape.

Binding sites

L1

L2

Binding sites

PROTEIN

Induced-fit model

Figure 2.11a The law of mass action (1 of 4)

Reaction at equilibrium

[PL][P] [L]

Keq

r2

r1

Rate of reaction inforward direction (r1)

rate of reaction inreverse direction (r2)

=

[PL]= Keq[P] [L]

Figure 2.11b The law of mass action (2 of 4)

[PL]

Add more P or L to system

Equilibrium disturbed

Keq

r2

r1

[PL][P] [L] < Keq

Figure 2.11c The law of mass action (3 of 4)

[PL][P] [L]

Keq

r2

r1

Reaction rate r1 increases to convert some of addedP or L into product PL

Figure 2.11d The law of mass action (4 of 4)

[PL][P] [L]

Keq

r2

r1

The ratio of bound to unboundis always the same at equilibrium.

Equilibrium restored when once more[PL]= Keq[P] [L]

Dissociation Constant Indicates Affinity

• Dissociation constant (Kd) likely of a protein and ligand remaining apart or dissociated, opposite of equilibrium constant, low dissociation constant = high affinity btw protein and ligand

• Competitors: ligands (and related molecules) compete for the binding site on proteins

• Agonists: competitive ligands that bind and stimulate• Antagonists: inhibitors


Multiple Factors Affect Protein Binding

• Isoforms: multiple forms of a protein (Ex. Hemoglobin)• Activation

– Proteolytic activation (lysis)– Cofactors: ion or molecule required for protein to function

properly, changes shape to allow ligand(s) to bind to binding site (Ca2+, Mg 2+, etc.)

• Modulation/modulators: ability of protein to bind a ligand (1) and initiate response (2) can be regulated by:– Chemical modulators: molecules– Physical factors (temp, pH, etc.)


Modulators: molecules alter protein binding ability or acidity: Inhibitors and activators– Antagonists (inhibitors): chemical modulators that

bind to a protein and decrease its activity– Activator: binding of molecule results in enhanced

activity– Competitive inhibitor: binds to the protein’s binding site and

block another ligand from binding (considered reversible, meaning that it is not permanent). Irreversible antagonists cannot be displaced

– Allosteric inhibitor/activator: binds to a protein (not at the binding site) and alters its shape so that a ligand can either bind (activator) or not bind (inhibitor)

– covalent modulators: atoms or functional groups that bind to a protein and alter the properties (phosphate group)

Figure 2.12a ESSENTIALS – Protein Activation and Inhibition

ACTIVATION

Inactive protein Active protein

Peptide fragments

Proteolytic activation: Protein is inactive until peptide fragments are removed.

Figure 2.12c ESSENTIALS – Protein Activation and Inhibition

ACTIVATION

Cofactors are required for an active binding site.

ACTIVEPROTEIN

INACTIVEPROTEIN

Bindingsite

COFACTORL1

L2

Without the cofactorattached, the protein is

not active.

Cofactor bindingactivates the protein.

Table 2.3 Factors That Affect Protein Binding

Figure 2.12d ESSENTIALS – Protein Activation and Inhibition

INHIBITION

Competitive inhibitor

A competitive inhibitor blocks ligand bindingat the binding site.

L1

L2

ACTIVEPROTEIN

INACTIVEPROTEIN

Figure 2.12e ESSENTIALS – Protein Activation and Inhibition

INHIBITION

Allosteric inhibitor is a modulator that binds toprotein away from binding site and inactivates thebinding site.

INACTIVEPROTEIN

ACTIVEPROTEIN

Ligand Ligand

Binding site

Allostericinhibitor

Protein withoutmodulator is active.

Modulator binds to protein awayfrom binding site and inactivates

the binding site.

Figure 2.12b ESSENTIALS – Protein Activation and Inhibition

Allosteric activator is a modulator that binds toprotein away from binding site and turns it on.

LigandLigand

Bindingsite

Allosteric activator

INACTIVEPROTEIN ACTIVE

PROTEIN

Protein withoutmodulator is inactive.

Modulator binds to proteinaway from binding site.

AA

ACTIVATION

Figure 2.13a ESSENTIALS – Factors That Influence Protein Activity

Temperature and pH

GRAPH QUESTION

Temperature and pH changes may disrupt protein structure and cause loss of function.

Active proteinin normal tertiaryconformation

Is the protein more activeat 30°C or at 48°C?

Denaturedprotein

This protein denaturesaround 50°C.

Temperature (°C)20 30 40 50 60

Rate

of

pro

tein

act

ivit

y

Body Regulates the Amount of Protein in Cells

• The amount of protein can be up-regulated (increased) or down-regulated (decreased) to control the amount of a protein=change physiological processes

• up-regulation: increased production of new proteins• down-regulation: decreased production or degradation

(removal) of proteins


Figure 2.13b ESSENTIALS – Factors That Influence Protein Activity

Amount of Protein

Reaction rate depends on the amount of protein.The more protein present, the faster the rate.

Protein concentration

In this experiment, the ligand amount remains constant.

GRAPH QUESTIONS

A B C

3

2

1

0

Resp

on

se r

ate

(m

g/s

ec)

• What is the rate when the protein concentration is equal to A?• When the rate is 2.5 mg/sec, what is the protein concentration?

Reaction Rate Can Reach a Maximum

• Concentration of ligand• Maximum reaction rate

– Saturation: all ligands are bound to protein molecules– can occur in enzymes, membrane transporters, receptors,

binding proteins, and immunoglobulins


Figure 2.13c ESSENTIALS – Factors That Influence Protein Activity

Amount of Ligand

If the amount of binding protein is held constant, thereaction rate depends on the amount of ligand, up to thesaturation point.

Maximum rate at saturationR

esp

on

se r

ate

(m

g/s

ec)

What is the rate whenthe ligand concentrationis 200 mg/mL?

GRAPH QUESTION

Ligand concentration (mg/mL)25 50 75 100 125 150 175

In this experiment, the amount of binding protein wasconstant. At the maximum rate, the protein is said to besaturated.

4

3

2

1

0

ch2

Documents

carbon fatty acids

acid group

fatty acid fatty acid

different amino acids

monounsaturated fatty

essential amino acids

palmitic acid

carbon biomolecules