Chapter 5

The Structure and Function of Macromolecules

• Overview: The Molecules of Life– Another level in the hierarchy of biological

organization is reached when small organic molecules are joined together

• Macromolecules– Are large molecules composed of smaller

molecules

– Are complex in their structures

• 4 main classes of macromolecules:

• carbohydrates

• lipids

• proteins

• nucleic acids

Most macromolecules are polymers, built from smaller molecules (repeating units)

• three of the classes of life’s organicmolecules are polymers

– Carbohydrates

– Proteins

– Nucleic acids

• A polymer– Is a long molecule consisting of many similar

building blocks called monomers

The Synthesis and Breakdown of Polymers

• Monomers form larger molecules by condensation reactions called dehydration(synthesis) reactions

(a) Dehydration reaction in the synthesis of a polymer

HO H1 2 3 HO

HO H1 2 3 4

H

H2O

Short polymer Unlinked monomer

Longer polymer

Dehydration removes a watermolecule, forming a new bond

• Polymers can disassemble by hydrolysis

(b) Hydrolysis of a polymer

HO 1 2 3 H

HO H1 2 3 4

H2O

HHO

Hydrolysis adds a watermolecule, breaking a bond

The Diversity of Polymers

• Each class of polymer is formed from a specific set of monomers

• Although organisms share the same limited number of monomer types, each organism is unique based on the arrangement of monomers into polymers

• An immense variety of polymers can be built from a small set of monomers

Carbohydrates

• Elements: C, H, O

• General formula: CH2O (ex. C6H12O6)

• Include: – sugars and their polymers (ex. starches)

• Functions: – Energy (fuel & storage)

– Raw materials (for synthesis of other organic molecules)

– Structural materials

Sugars

• Most names end in “-ose”

• Classified by # of carbons:

– 6C = hexose (ex. Glucose)

– 5C = pentose (ex. deoxyribose & ribose)

– 3C = triose (ex. Glyceraldehyde

• Characteristic functional groups:– Hydroxyl (multiple)

– Carbonyl (one; in linear form only)

Sugars

• Aldehyde vs. Ketone sugars:– Depends on location of carbonyl group

– Sugars start out as linear molecules!

– If carbonyl located on C1 (at end) = aldehyde sugar = aldose (ex. Glucose)

– If carbonyl located on C2 = ketone sugar = ketose (ex. Fructose)

Sugars

• Linear vs. ring structure:– Equilibrium greatly favors ring

– 5C & 6C sugars form rings in aqueous solutions (i.e. in cells!)

– Carbons are numbered!

– Spatial arrangement of parts around asymmetric carbon becomes important

– Many isomers result from arrangement of hydroxyl groups (“down, down, up, down”)

– Glucose vs. galactose (1 asymmetric carbon)

Sugars

• Monosaccharides

– simplest sugars = monomers• Ex. Glucose, fructose, galactose

– can be:

• used directly for fuel

• converted into other organic molecules

• combined into polymers

• Examples of monosaccharides

Triose sugars(C3H6O3)

Pentose sugars(C5H10O5)

Hexose sugars(C6H12O6)

H C OH

H C OH

H C OH

H C OH

H C OH

H C OH

HO C H

H C OH

H C OH

H C OH

H C OH

HO C H

HO C H

H C OH

H C OH

H C OH

H C OH

H C OH

H C OH

H C OH

H C OH

H C OH

C OC O

H C OH

H C OH

H C OH

HO C H

H C OH

C O

H

H

H

H H H

H

H H H H

H

H H

C C C COOOO

Ald

oses

Glyceraldehyde

RiboseGlucose Galactose

Dihydroxyacetone

Ribulose

Ket

oses

Fructose

• Monosaccharides– May be linear or can form rings

H

H C OH

HO C H

H C OH

H C OH

H C

OC

H

1

2

3

4

5

6

H

OH

4C

6CH2OH 6CH2OH

5C

HOH

C

H OH

H2 C

1C

H

O

H

OH

4C

5C

3 C

H

HOH

OH

H2C

1 C

OH

H

CH2OH

H

H

OHHO

H

OH

OH

H5

3 2

4

Linear and ring forms: • Chemical equilibrium between linear & ring structures

greatly favors ring formation.• To form the glucose ring, carbon 1 bonds to the oxygen

attached to carbon 5.

OH 3

O H OO

6

1

• Disaccharides– Consist of two monosaccharides

– Are joined by a glycosidic linkage

• Examples of disaccharides Dehydration synthesis of maltose: glycosidic link joins carbon 1 of glucose to carbon 4 of another glucose

Dehydration synthesis of sucrose: glycosidic link joins carbon 1 of glucose to carbon 2 of fructose

(a)

(b)

H

HO

H

HOH H

OH

O H

OH

CH2OH

H

HO

H

HOH H

OH

O H

OH

CH2OH

H

O

H

HOH H

OH

O H

OH

CH2OH

H

H2O

H2O

H

H

O

H

HOH

OH

O HCH2OH

CH2OH HO

OHH

CH2OH

HOH H

H

HO

OHH

CH2OH

HOH H

O

O H

OHH

CH2OH

HOH H

O

HOH

CH2OH

H HO

O

CH2OH

H

H

OH

O

O

1 2

1 41– 4

glycosidiclinkage

1–2glycosidic

linkage

Glucose

Glucose Glucose

Fructose

Maltose

Sucrose

OH

H

H

Polysaccharides

• Are polymers of sugars

• Serve many roles in organisms

Storage Polysaccharides

• Starch– Is a polymer consisting

entirely of glucose monomers

– Is the major storage form of glucose in plants

Chloroplast Starch

Amylose Amylopectin

1 m

Starch: a plant polysaccharide

• Glycogen– Also consists of

glucose monomers

– Is the major storage form of glucose in animals

Mitochondria Giycogen granules

0.5 m

Glycogen: an animal polysaccharide

Glycogen

Structural Polysaccharides• Cellulose

– Is a also polymer of glucose

– Has different glycosidic linkages than starch

(c) Cellulose: 1– 4 linkage of glucose monomers

H O

O

CH2OH

HOH H

H

OH

OHH

H

HO

4

C

C

C

C

C

C

H

H

H

HO

OH

H

OH

OH

OH

H

O

CH2OH

HH

H

OH

OHH

H

HO4 OH

CH2OH

O

OH

OH

HO41

O

CH2OH

O

OH

OH

O

CH2OH

O

OH

OH

CH2OH

O

OH

OH

O O

CH2OH

O

OH

OH

HO 4O

1

OH

O

OH OHO

CH2OH

O

OH

O OH

O

OH

OH

(a) and glucose ring structures

(b) Starch: 1– 4 linkage of glucose monomers

1

glucose glucose

CH2OH

CH2OH

1 4 41 1

– Cellulose is a major component of the tough cell walls that enclose plant cells

Plant cells

0.5 m

Cell walls

Cellulose microfibrils in a plant cell wall Microfibril

CH2OH

CH2OH

OHOH

OO

OHOCH2OH

OO

OHO

CH2OH OH

OH OHO

O

CH2OHO

OOH

CH2OH

OO

OH

O

O

CH2OHOH

CH2OHOHOOH OH OH OH

O

OH OH

CH2OH

CH2OH

OHO

OH CH2OH

OO

OH CH2OH

OH

Glucose monomer

O

O

O

O

O

O

Parallel cellulose molecules areheld together by hydrogenbonds between hydroxyl

groups attached to carbonatoms 3 and 6.

About 80 cellulosemolecules associate

to form a microfibril, themain architectural unitof the plant cell wall.

A cellulose moleculeis an unbranched glucose polymer.

OH

OH

O

OOH

Cellulosemolecules

• Cellulose is difficult to digest– Cows have microbes in their stomachs to facilitate

this process

• Chitin, another important structuralpolysaccharide– arthropods (exoskeletons) & fungi (cell walls)– 2nd most abundant after cellulose; most organisms

can’t digest it (N-containing side group)– leathery in pure form; becomes hardened by CaCO3

(a) The structure of thechitin monomer.

O

CH2OH

OHHH OH

HNHCCH3

O

H

H

(b) Chitin forms the exoskeletonof arthropods. This cicada is molting, shedding its old exoskeleton and emergingin adult form.

(c) Chitin is used to make a strong and flexible surgicalthread that decomposes afterthe wound or incision heals.

OH

• A.K.A. fats or triglycerides• diverse group of hydrophobic molecules• are the one class of large biological molecules

that do not consist of polymers– Share the common trait of being hydrophobic

Lipids

Lipids • Are constructed from two types of smaller

molecules, a single glycerol and usually three fatty acids

(b) Fat molecule (triacylglycerol)

H HH H

HHH H

HH H H

HH

HHO

H O HC

C

C

H

H OH

OH

H

HH

HH

H H HH

H H H H HH

H

HCCCCC

CCCCC

CC

CCC C

Glycerol

Fatty acid(palmitic acid)

HH

H

H

H H HH

HH

HH

HH H H

HH H H

HHHHHHHHHHHHHHHH

H

HH H H H H H H H H H H H H H

H

HHHHHHHHHHHHHH

H H H H H H H H H H H H H H HH

HHHHHHHHHHHHHHH

HO

OO

O

OC

C

C C C C C C C C C C C C C C C C C

C

CCCCCCCCCCCCCCCC

C C C C C C C C C C C C C C CO

O

(a) Dehydration reaction in the synthesis of a fatEster linkage

• Fatty acids vary in:– length– number– locations of double bonds they contain

• Saturated fatty acids– Have the maximum number of hydrogen atoms

possible– Have no double bonds– Are solid at room temperatures. Why??

(a) Saturated fat and fatty acid

Stearic acid

• Unsaturated fatty acids– Have one or more double bonds (causes “kink”)– Are liquid at room temperatures. Why??

(b) Unsaturated fat and fatty acidcis double bondcauses bending

Oleic acid

• Phospholipids– Have only two fatty acids

– Have a phosphate group instead of a third fatty acid

• Phospholipid structure– Consists of a hydrophilic “head” and hydrophobic

“tails”

CH2

OPO OO

CH2CHCH2

OO

C O C O

Phosphate

Glycerol

(a) Structural formula (b) Space-filling model

Fatty acids

(c) Phospholipid symbol

Hydrophilichead

Hydrophobictails

–

CH2 Choline+N(CH3)3

• The structure of phospholipids– Results in a bilayer arrangement found in cell

membranes

Hydrophilichead

WATER

WATER

Hydrophobictail

• Steroids– Are lipids characterized by a carbon skeleton

consisting of 4 fused rings

• Cholesterol– steroid found in cell membranes

– precursor for some hormones

HO

CH3

CH3

H3C CH3

CH3

• have many structures, resulting in a wide range of functions– Have many roles inside the cell

Proteins

• An overview of protein functions

Animation: Structural ProteinsAnimation: Structural Proteins

Animation: Storage ProteinsAnimation: Storage Proteins

Animation: Transport ProteinsAnimation: Transport Proteins

Animation: Receptor ProteinsAnimation: Receptor Proteins

Animation: Contractile ProteinsAnimation: Contractile Proteins

Animation: Defensive ProteinsAnimation: Defensive Proteins

Animation: Hormonal ProteinsAnimation: Hormonal Proteins

Animation: Sensory ProteinsAnimation: Sensory Proteins

Animation: Gene Regulatory ProteinsAnimation: Gene Regulatory Proteins

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Polypeptides• Polypeptides are polymers of amino acids

• A protein consists of one or more polypeptides– All proteins are polypeptides, but not all

polypeptides are proteins

Amino Acid Monomers

• Amino acids are organic molecules possessing both carboxyl and amino groups– 20 different amino acids make up proteins

– properties differ based on different side chains called R groups

Fig. 5-UN1

Aminogroup

Carboxylgroup

carbon(asymmetric)

Nonpolar

Glycine(Gly or G)

Alanine(Ala or A)

Valine(Val or V)

Leucine(Leu or L)

Isoleucine(Ile or I)

Methionine(Met or M)

Phenylalanine(Phe or F)

Tryptophan(Trp or W)

Proline(Pro or P)

Polar

Asparagine(Asn or N)

Glutamine(Gln or Q)

Serine(Ser or S)

Threonine(Thr or T)

Cysteine(Cys or C)

Tyrosine(Tyr or Y)

Acidic

Arginine(Arg or R)

Histidine(His or H)

Aspartic acid(Asp or D)

Glutamic acid(Glu or E)

Lysine(Lys or K)

Basic

Electricallycharged

Amino Acid Polymers• Amino acids are linked by peptide bonds

OH

DESMOSOMES

DESMOSOMESDESMOSOMES

OH

CH2

C

N

H

CH O

H OH OH

Peptidebond

OH

OH

OH

H H

HH

H

HH

H

H

H H

H

N

N N

N N

SHSide

chains

SH

OO

O O O

H2O

CH2 CH2

CH2 CH2 CH2

C C C C C C

C CC C

Peptidebond

Amino end(N-terminus)

Backbone

(a)

(b) Carboxyl end(C-terminus)

Protein Conformation and Function

• The amino acid sequence determines a protein’s specific conformation (shape)

• A protein’s shape determines how it functions

• The amino acid sequences of polypeptides– Were first determined using chemical means

– Can now be determined by automated machines

• Two models of protein conformation

(a) A ribbon model

(b) A space-filling model

Groove

Groove

• Shape determines function!– Example: enzymes act as catalysts (speed up

chemical reactions) by binding with specific molecules (substrates); the shape of the enzyme’s active site matches the shape of the substrate.

Substrate(sucrose)

Enzyme (sucrase)

Glucose

OH

H O

H2OFructose

2Active site

Four Levels of Protein Structure

• Primary structure– unique amino acid

sequence in a polypeptide

–

Amino acid subunits

+H3NAmino end

oCarboxyl end

oc

Gly ProThr GlyThr

Gly

GluSeuLysCysProLeu

MetVal

Lys

ValLeu

AspAla Val ArgGly

SerPro

Ala

Gly

lleSerProPheHis Glu His

Ala

GluValValPheThrAla

Asn

AspSer

Gly ProArg

ArgTyrThr

lleAla

Ala

Leu

LeuSer

ProTyrSerTyrSerThrThr

AlaVal

ValThrAsn ProLysGlu

ThrLys

SerTyrTrpLysAlaLeu

Glu Lle Asp

O C helix

pleated sheet

Amino acidsubunits NC

H

CO

C N

H

CO H

R

C NH

C

O H

CR

NHH

R CO

R

CH

NH

C

O HN

CO

R

CH

NH

H

CR

C

O

C

O

C

NH

H

R

CCO

NH

H

CR

C

O

NH

R

CH C

ONH H

CR

C

ONH

R

CH C

ONH H

CR

C

O

N H

H C RN H O

O C N

C

RC

H O

CHR

N HO C

RC

H

N H

O CH C R

N H

CC

N

R

H

O C

H C R

N H

O C

RC

H

H

CR

NH

CO

C

NH

R

CH C

ONH

C

• Secondary structure– folding or coiling of the polypeptide into a

repeating configuration

– includes the helix and the pleated sheet

H H

• Tertiary structure

– overall three-dimensional shape of a polypeptide

– Results from interactions between amino acids and R groups

CH2CH

OHOCHO

CH2

CH2 NH3+ C-O CH2

O

CH2SSCH2

CH

CH3

CH3

H3CH3C

Hydrophobic interactions and van der Waalsinteractions

Polypeptidebackbone

Hyrdogenbond

Ionic bond

CH2

Disulfide bridge

• Quaternary structure– overall protein structure that results from the

aggregation of two or more polypeptide subunits

Polypeptidechain

Collagen Chains

ChainsHemoglobin

IronHeme

• The four levels of protein structure

+H3NAmino end

Amino acidsubunits

helix

Let’s look at the animation!

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Sickle-Cell Disease: A Simple Change in Primary Structure

• Sickle-cell disease

– Results from a single amino acid substitution in the protein hemoglobin

• Hemoglobin structure and sickle-cell disease

Fibers of abnormalhemoglobin deform cell into sickle shape.

Primary structure

Secondaryand tertiarystructures

Quaternary structure

Function

Red bloodcell shape

Hemoglobin A

Molecules donot associatewith oneanother, eachcarries oxygen.Normal cells arefull of individualhemoglobinmolecules, eachcarrying oxygen

10 m 10 m

Primary structure

Secondaryand tertiarystructures

Quaternary structure

Function

Red bloodcell shape

Hemoglobin S

Molecules interact with one another tocrystallize into a fiber, capacity to carry oxygen is greatly reduced.

subunit subunit

1 2 3 4 5 6 7 3 4 5 6 721

Normal hemoglobin Sickle-cell hemoglobin. . .. . . Exposed

hydrophobic region

Val ThrHis Leu Pro Glul Glu Val His Leu Thr Pro Val Glu

What Determines Protein Conformation?

• Protein conformation depends on the physical and chemical conditions of the protein’s environment

• Denaturation– when a protein unravels and loses its native

conformation

Denaturation

Renaturation

Denatured proteinNormal protein

The Protein-Folding Problem

• Most proteins– Probably go through several intermediate states on

their way to a stable conformation– Can sometimes get misfolded along the way

• Chaperonins– Are protein molecules that assist in the proper

folding of other proteins

Hollowcylinder

Cap

Chaperonin(fully assembled)

Steps of ChaperoninAction:

An unfolded poly-peptide enters the cylinder from one end.

The cap attaches, causing the cylinder to change shape insuch a way that it creates a hydrophilic environment for the folding of the polypeptide.

The cap comesoff, and the properlyfolded protein is released.

Correctlyfoldedprotein

Polypeptide

2

1

3

• X-ray crystallography– Is used to determine a protein’s three-

dimensional structureX-raydiffraction pattern

Photographic filmDiffracted X-rays

X-raysource

X-raybeam

Crystal Nucleic acid Protein

(a) X-ray diffraction pattern (b) 3D computer model

Nucleic acids

• store and transmit hereditary information

• make up genes (units of inheritance)– program the amino acid sequence of

polypeptides

• There are two types of nucleic acids– Deoxyribonucleic acid (DNA)

– Ribonucleic acid (RNA)

• DNA– Stores information

for the synthesis of specific proteins

– Directs RNA synthesis

– Directs protein synthesis through RNA

1

2

3

Synthesis ofmRNA in the nucleus

Movement of mRNA into cytoplasm via nuclear pore

Synthesisof protein

NUCLEUSCYTOPLASM

DNA

mRNA

Ribosome

AminoacidsPolypeptide

mRNA

Structure of Nucleic Acids

• Nucleic acids exist as polymers called polynucleotides

(a) Polynucleotide, or nucleic acid

3’C

5’ end

5’C

3’C

5’C

3’ endOH

O

O

O

O

• Each polynucleotide consists of monomers called nucleotides

Nitrogenousbase

Nucleoside

O

O

O

O P CH2

5’C

3’CPhosphategroup Pentose

sugar

(b) Nucleotide

O

• Nucleotide monomers are made up of nucleosides and phosphate groups

(c) Nucleoside components

CHCH

Uracil (in RNA)U

Ribose (in RNA)

Nitrogenous basesPyrimidines

CN

NCO

H

NH2

CHCH

OC

NH

CHHN

CO

CCH3

N

HNC

C

HO

O

CytosineC

Thymine (in DNA)T

NHC

N C

C N

C

CHN

NH2 ON

HCNHH

C C

N

NHC NH2

AdenineA

GuanineG

Purines

OHOCH2

HH H

OH

H

OHOCH2

HH H

OH

H

Pentose sugars

Deoxyribose (in DNA) Ribose (in RNA)OHOH

CHCH

Uracil (in RNA)U

4’

5”

3’OH H

2’

1’

5”

4’

3’ 2’

1’

• Nucleotide polymers are made up of nucleotides linked by the–OH group on the 3´carbon of one nucleotide and the phosphate on the 5´ carbon on the next

Nitrogenousbase

Nucleoside

O

O

O

O P CH2

5’C

3’CPhosphategroup Pentose

sugar

(b) Nucleotide

O

• The sequence of bases along a nucleotide polymer is unique for each gene

DNA Double Helix

• Cellular DNA molecules– Have two polynucleotides that spiral around an

imaginary axis

– Form a double helix

• The DNA double helix– Consists of two antiparallel nucleotide strands

3’ end

Sugar-phosphatebackbone

Base pair (joined byhydrogen bonding)Old strands

Nucleotideabout to be added to a new strand

A

3’ end

3’ end

5’ end

Newstrands

3’ end

5’ end

5’ end

• The nitrogenous bases in DNA– Form hydrogen bonds in a complementary fashion

(A with T only, and C with G only)

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The Theme of Emergent Properties in the Chemistry of Life: A Review

• Higher levels of organization

– Result in the emergence of new properties

• Organization

– Is the key to the chemistry of life