Chapter 5

The Structure and Function of Macromolecules

1

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

organization is reached when small organic molecules are joined together

– Atom ---> molecule --- compound– Big Idea 2: Biological systems utilize Free

Energy and molecular Building Blocks to grow, reproduce, and maintain dynamic homeostasis.

– Big Idea 3: Biological systems store, retrieve, transmit, and respond to information essential to life processes.

2

Macromolecules

•Most macromolecules are polymers, built from monomers• Four classes of life’s organic molecules are polymers– Carbohydrates– Proteins– Nucleic acids– Lipids

3

• A polymer– Is a long molecule consisting of many

similar building blocks called monomers– Specific monomers make up each

macromolecule– E.g. amino acids are the monomers for

proteins

4

The Synthesis and Breakdown of Polymers

• Monomers form larger molecules by condensation reactions called dehydration synthesis

5

(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

Figure 5.2A

The Synthesis and Breakdown of Polymers

• Polymers can disassemble by– Hydrolysis (addition of water molecules)

6

(b) Hydrolysis of a polymer

HO 1 2 3 H

HO H1 2 3 4

H2O

HHO

Hydrolysis adds a watermolecule, breaking a bond

Figure 5.2B

• 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

7

Sugars• Monosaccharides– Are the simplest sugars– Can be used for fuel– Can be converted into other organic molecules– Can be combined into polymers

8

Carbohydrates• Serve as fuel and building material• Include both sugars and their polymers

(starch, cellulose, etc.)

• Examples of monosaccharides

9

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

Keto

ses

FructoseFigure 5.3

• Monosaccharides– May be linear– Can form rings

10

H

H C OH

HO C H

H C OH

H C OH

H C

O

C

H

1

2

3

4

5

6

H

OH

4C

6CH2OH 6CH2OH

5C

HOH

C

H OH

H

2 C

1C

H

O

H

OH

4C

5C

3 C

H

HOH

OH

H

2C

1 C

OH

H

CH2OH

H

H

OHHO

H

OH

OH

H5

3 2

4

(a) Linear and ring forms. Chemical equilibrium between the linear and ring structures greatly favors the formation of rings. To form the glucose ring, carbon 1 bonds to the oxygen attached to carbon 5.

OH3

O H OO

6

1

Figure 5.4

11

Dehydration reaction in the synthesis of maltose. The bonding of two glucose units forms maltose. The glycosidic link joins the number 1 carbon of one glucose to the number 4 carbon of the second glucose. Joining the glucose monomers in a different way would result in a different disaccharide.

Dehydration reaction in the synthesis of sucrose. Sucrose is a disaccharide formed from glucose and fructose.Notice that fructose,though a hexose like glucose, forms a five-sided ring.

(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 H

CH2OH

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

Figure 5.5

• Disaccharides– Consist of two monosaccharides– Are joined by a glycosidic linkage

Polysaccharides

• Polysaccharides– Are polymers of sugars– Serve many roles in organisms

12

Storage Polysaccharides

• Starch– Is a polymer

consisting entirely of glucose monomers

– Is the major storage form of glucose in plants

13

Chloroplast Starch

Amylose Amylopectin

1 m

(a) Starch: a plant polysaccharideFigure 5.6

• Glycogen– Consists of glucose monomers– Is the major storage form of glucose in animals

14

Mitochondria Giycogen granules

0.5 m

(b) Glycogen: an animal polysaccharide

Glycogen

Figure 5.6

Structural Polysaccharides

• Cellulose– Is a polymer of

glucose

15

– 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

OHOHOH

H

O

CH2OH

HH

H

OH

OHH

H

HO

4 OH

CH2OH

OOH

OH

HO

41

O

CH2OH

OOH

OH

O

CH2OH

OOH

OH

CH2OH

O

OH

OH

O O

CH2OH

OOH

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

Figure 5.7 A–C

– Is a major component of the tough walls that enclose plant cells

16

Plant cells

0.5 m

Cell walls

Cellulose microfibrils in a plant cell wall

Microfibril

CH2OH

CH2OH

OH

OH

OO

OHOCH2OH

O

OOH

OCH2OH OH

OH OHO

O

CH2OH

OO

OH

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

Figure 5.8

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

this process

17

Figure 5.9

• Chitin, another important structural polysaccharide– Is found in the exoskeleton of arthropods– Can be used as surgical thread

18

(a) The structure of the chitin monomer.

O

CH2OH

OHHH OH

H

NH

CCH3

O

H

H

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

(c) Chitin is used to make a strong and flexible surgical

thread that decomposes after the wound or incision heals.

OH

Figure 5.10 A–C

Lipids• Lipids are a diverse group of hydrophobic

molecules• Lipids– Are the one class of large biological

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

19

Triglycerides (Fats)– Are constructed from two types of smaller molecules, a

single glycerol and usually three fatty acids– Vary in the length and number and locations of double

bonds they contain

20

(a) Saturated fat and fatty acid

Stearic acid

Figure 5.12

(b) Unsaturated fat and fatty acidcis double bondcauses bending

Oleic acid

Figure 5.12

21

• Saturated fatty acids– Have the maximum number of hydrogen

atoms possible– Have no double bonds

• Unsaturated fatty acids– Have one or more double bonds

• Phospholipids– Have only two fatty acids– Have a phosphate group instead of a third

fatty acid

22

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

hydrophobic “tails”

23

CH2

O

PO O

O

CH2CHCH2

OO

C O C O

Phosphate

Glycerol

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

Fatty acids

(c) Phospholipid symbol

Hyd

rop

hob

i c t

ails

Hydrophilichead

Hydrophobictails

–

Hyd

rop

hi li c

head

CH2 Choline+

Figure 5.13

N(CH3)3

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

membranes

24

Hydrophilichead

WATER

WATER

Hydrophobictail

Figure 5.14

Steroids• Steroids– Are lipids characterized by a carbon skeleton

consisting of four fused rings

25

• E.g. Cholesterol– Is found in cell membranes– Is a precursor for some hormones

HO

CH3

CH3

H3C CH3

CH3

Figure 5.15

Proteins

• Proteins have many structures, resulting in a wide range of functions

• Proteins do most of the work in cells and act as enzymes

• Proteins are made of monomers called amino acids

26

• An overview of protein functions

27

Table 5.1

• Enzymes– Are a type of protein that acts as a catalyst,

speeding up chemical reactions

28

Substrate(sucrose)

Enzyme (sucrase)

Glucose

OH

H O

H2O

Fructose

3 Substrate is convertedto products.

1 Active site is available for a molecule of substrate, the

reactant on which the enzyme acts.

Substrate binds toenzyme.

22

4 Products are released.Figure 5.16

Polypeptides• Polypeptides– Are polymers (chains) of amino acids

• A protein– Consists of one or more polypeptides

• Amino acids– Are organic molecules possessing both carboxyl

and amino groups– Differ in their properties due to differing side

chains, called R groups

29

Twenty Amino Acids

• 20 different amino acids make up proteins

30

O

O–

H

H3N+ C C

O

O–

H

CH3

H3N+ C

H

C

O

O–

CH3 CH3

CH3

C C

O

O–

H

H3N+

CH

CH3

CH2

C

H

H3N+

CH3CH3

CH2

CH

C

H

H3N+

C

CH3

CH2

CH2

CH3N+

H

C

O

O–

CH2

CH3N+

H

C

O

O–

CH2

NH

H

C

O

O–

H3N+ C

CH2

H2C

H2N C

CH2

H

C

Nonpolar

Glycine (Gly) Alanine (Ala) Valine (Val) Leucine (Leu) Isoleucine (Ile)

Methionine (Met) Phenylalanine (Phe)

C

O

O–

Tryptophan (Trp) Proline (Pro)

H3C

Figure 5.17

S

O

O–

31

O–

OH

CH2

C C

H

H3N+

O

O–

H3N+

OH CH3

CH

C C

HO–

O

SH

CH2

C

H

H3N+ C

O

O–

H3N+

C C

CH2

OH

H H H

H3N+

NH2

CH2

OC

C CO

O–

NH2 O

C

CH2

CH2

C CH3N

+

O

O–

O

Polar

Electricallycharged

–O O

C

CH2

C CH3N

+

H

O

O–

O– O

C

CH2

C CH3N

+

H

O

O–

CH2

CH2

CH2

CH2

NH3+

CH2

C CH3N

+

H

O

O–

NH2

C NH2+

CH2

CH2

CH2

C CH3N

+

H

O

O–

CH2

NH+

NHCH2

C CH3N

+

H

O

O–

Serine (Ser) Threonine (Thr)Cysteine

(Cys)Tyrosine

(Tyr)Asparagine

(Asn)Glutamine

(Gln)

Acidic Basic

Aspartic acid (Asp)

Glutamic acid (Glu)

Lysine (Lys) Arginine (Arg) Histidine (His)

Amino Acid Polymers

• Amino acids– Are linked by peptide bonds

32

Protein Conformation and Function

• A protein’s specific conformation (shape) determines how it functions

33

Four Levels of Protein Structure

• Primary structure– Is the unique sequence

of amino acids in a polypeptide

34

Figure 5.20–

Amino acid

subunits

+H3NAmino

end

oCarboxyl end

oc

GlyProThrGlyThr

Gly

GluSeuLysCysProLeu

MetVal

Lys

ValLeu

AspAlaValArgGly

SerPro

Ala

Gly

lle

SerProPheHisGluHis

Ala

GluValValPheThrAla

Asn

AspSer

GlyProArg

ArgTyrThr

lleAla

Ala

Leu

LeuSer

ProTyrSerTyrSerThr

Thr

Ala

ValVal

ThrAsnProLysGlu

ThrLys

SerTyrTrpLysAlaLeu

GluLleAsp

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

repeating configuration– Includes the helix and the pleated sheet

35

O C helix

pleated sheetAmino acid

subunitsNCH

C

O

C N

H

CO H

R

C NH

C

O H

C

R

N

HH

R C

O

R

C

H

NH

C

O H

NCO

R

C

H

NH

H

C

R

C

O

C

O

C

NH

H

R

C

C

ON

HH

C

R

C

O

NH

R

C

H C

ON

HH

C

R

C

O

NH

R

C

H C

ON

HH

C

R

C

O

N H

H C R

N HO

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

C

RN

H

CO

C

NH

R

C

H C

O

N

H

C

H H

Figure 5.20

• Tertiary structure– Is the overall three-dimensional shape of a

polypeptide– Results from interactions between amino acids

and R groups

36

CH2CH

OH

O

CHO

CH2

CH2 NH3+ C-O CH2

O

CH2SSCH2

CH

CH3

CH3

H3C

H3C

Hydrophobic interactions and van der Waalsinteractions Polypeptid

ebackbone

Hyrdogenbond

Ionic bond

CH2

Disulfide bridge

• Quaternary structure– Is the overall protein structure that results from

the aggregation of two or more polypeptide subunits

37

Polypeptidechain

Collagen

Chains

ChainsHemoglobin

IronHeme

Review of Protein Structure

38

+H3NAmino end

Amino acidsubunits

helix

39

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 SMolecules 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 . . .. . .

Figure 5.21

Exposed hydrophobic

region

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

Sickle-Cell Disease: A Simple Change in Primary Structure

What Determines Protein Conformation?

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

• Temperature, pH, etc. affect protein structure

40

•Denaturation is when a protein unravels and loses its native conformation(shape)

41

Denaturation

Renaturation

Denatured protein

Normal protein

Figure 5.22

The Protein-Folding Problem

• Most proteins– Probably go through several intermediate

states on their way to a stable conformation

– Denaturated proteins no longer work in their unfolded condition

– Proteins may be denaturated by extreme changes in pH or temperature

42

• Chaperonins– Are protein molecules that assist in the proper

folding of other proteins

43

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

Figure 5.23

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

dimensional structure

44

X-raydiffraction pattern

Photographic filmDiffracted X-

raysX-ray

source

X-ray

beam

CrystalNucleic acid Protein

(a) X-ray diffraction pattern(b) 3D computer modelFigure 5.24

Nucleic Acids

• Nucleic acids store and transmit hereditary information

• Genes– Are the units of inheritance– Program the amino acid sequence of

polypeptides– Are made of nucleotide sequences on

DNA

45

The Roles of Nucleic Acids• There are two types of nucleic acids– Deoxyribonucleic acid (DNA)– Ribonucleic acid (RNA)

46

Deoxyribonucleic Acid• DNA– Stores information for

the synthesis of specific proteins

– Found in the nucleus of cells

– Directs RNA synthesis (transcription)

– Directs protein synthesis through RNA (translation)

47

1

2

3

Synthesis of mRNA in the nucleus

Movement of mRNA into cytoplasm

via nuclear pore

Synthesisof protein

NUCLEUSCYTOPLASM

DNA

mRNA

Ribosome

AminoacidsPolypeptide

mRNA

Figure 5.25

The Structure of Nucleic Acids– Consists of monomers called

nucleotides– Sugar + phosphate + nitrogen

base

48

(a) Polynucleotide, or nucleic acid

3’C

5’ end

5’C

3’C

5’C

3’ endOH

Figure 5.26

O

O

O

O

Nitrogenousbase

Nucleoside

O

O

O

O P CH2

5’C

3’CPhosphate

group Pentosesugar

(b) NucleotideFigure 5.26

O

The Nitrogen bases: A, T, U, G, and C

• Purine Rings:• Adenine, Guanine

• Pyrimidine Rings:• Cytosine, Uracil, thymine

49

Nucleotide Polymers• Nucleotide polymers are linked by

phosphodiester bonds. – OH group on the 3´ carbon to phosphate of 5’

carbon on next molecule.

50

The DNA Double Helix• Cellular DNA molecules– Have two anti-parallel strands that spiral around

an imaginary axis forming a double helix– Are held together by hydrogen bonding between

nitrogen bases on anti-paralle strands

51

complementary base pair rules: A with T only in DNA/ A with U only in RNAC with G only

DNA and Proteins as Tape Measures of Evolution

• Molecular comparisons – Help biologists sort out the evolutionary

connections among species – We will come back to this in Investigation 3:

Using BLAST to compare DNA sequences to determine evolutionary sequences

52

Big Ideas 2 and 3

• Big Idea 2: Biological systems utilize Free Energy and molecular Building Blocks to grow, reproduce, and maintain dynamic homeostasis.

• Big Idea 3: Biological systems store, retrieve, transmit, and respond to information essential to life processes.

53