Chapter 5. The Structure and Function of Macromolecules

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Chapter 5

The Structure and Function of

Macromolecules

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• Overview: The Molecules of Life

– Another level in the hierarchy of biological

organization is reached when small organic molecules are joined together

(3)

• Macromolecules

– Are large molecules composed of smaller

molecules

(4)

• 4 main classes of macromolecules:

• carbohydrates

• lipids

• proteins

(5)

Most macromolecules are polymers, built from

smaller molecules (repeating units)

• three of the classes of life’s organic

molecules are polymers

– Carbohydrates

– Proteins

(6)

• A polymer

– Is a long molecule consisting of many similar

(7)

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 1 ₂ 3 HO H

HO 1 2 3 4 H

H

H₂O

Short polymer Unlinked monomer

Longer polymer Dehydration removes a water molecule, forming a new bond

(8)

• Polymers can disassemble by hydrolysis

(b) Hydrolysis of a polymer HO 1 2 3 H HO 1 2 3 4 H H₂O H HO

Hydrolysis adds a water molecule, breaking a bond

(9)

The Diversity of Polymers

• Each class of polymer is formed from a specific

(10)

• 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

(11)

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)

(12)

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)

(13)

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 =

(14)

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”)

(15)

Sugars

• Monosaccharides

–

_{simplest sugars = monomers}

• Ex. Glucose, fructose, galactose

–

_{can be:}

• _{used directly for}

_fuel

• _{converted into other}

_{organic molecules}

• _{combined into}

_polymers

(16)

• 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 O C 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 C O O O O A ld o s e s Glyceraldehyde Ribose Glucose Galactose Dihydroxyacetone Ribulose K e to s e s Fructose

(17)

• Monosaccharides

– May be linear or can form rings

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 4_C 6_CH 2OH 6CH₂OH 5C H OH C H OH H 2 _C 1_C H O H OH 4_C 5_C 3 _C H H OH OH H 2_C 1 _C OH H CH₂OH H H OH HO H OH OH H 5 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 O O 6 1

(18)

• Disaccharides

– Consist of two monosaccharides

(19)

• Examples of disaccharides

Dehydration synthesis of maltose: glycosidic link joins carbon 1of glucose to carbon 4of another glucose Dehydration synthesis of sucrose: glycosidic link joins carbon 1of glucose to carbon 2of fructose (a) (b) H HO H H OH H OH O _H OH CH₂OH H HO H H OH H OH O _H OH CH₂OH H O H H OH H OH O _H OH CH₂OH H H₂O H₂O H H O H HO H OH O H CH₂OH CH₂OH HO OH H CH₂OH H OH H H HO OH H CH₂OH H OH H O O _H OH H CH₂OH H OH H O H OH CH₂OH H HO O CH₂OH H H OH O O 1 2 1 _glycosidic1– 4 4 linkage 1–2 glycosidic linkage Glucose Glucose Glucose Fructose Maltose Sucrose OH H H

(20)

Polysaccharides

• Are polymers of sugars

(21)

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

(22)

• 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

(23)

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 CH₂O H H OH H H OH OH H H HO 4 C C C C C C H H H HO OH H OH OH OH H O CH₂O H H H H OH OH H H HO 4 OH CH₂O H O OH OH HO 4 1 O CH2O H O OH OH O CH2O H O OH OH CH2O H O OH OH O _O CH₂O H O OH OH HO 4 O 1 OH O OH _OH O CH₂O H O OH O OH O OH OH

(a)  and  glucose ring structures

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

1  glucose  glucose CH₂O H CH₂O H 1 4 1 4 1

(24)

– 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 OH O H O O OH O CH2OH O O OH O CH2OH OH OH OH O O CH2OH O O O H CH2OH O O O H O O CH2OH OH CH2OH OH O OH _OH OH OH O OH OH CH2OH CH2OH OHO OH CH2OH O O OH CH2OH OH Glucose monomer O O O O O O

Parallel cellulose molecules are held together by hydrogen

bonds between hydroxyl groups attached to carbon

atoms 3 and 6.

About 80 cellulose molecules associate to form a microfibril, the

main architectural unit of the plant cell wall.

A cellulose molecule is an unbranched  glucose polymer. OH OH O O OH Cellulose molecules

(25)

• Cellulose is difficult to digest

– Cows have microbes in their stomachs to facilitate

(26)

• Chitin, another important structural

polysaccharide

– 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 the chitin monomer. O CH₂O H OH H H OH H NH C CH3 O H H

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

exoskeleton and emerging in adult form.

(c) Chitin is used to make a strong and flexible surgical thread that decomposes after the wound or incision heals.

(27)

• _{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

(28)

Lipids

• Are constructed from two types of smaller

molecules, a single glycerol and usually three

fatty acids

(b) Fat molecule (triacylglycerol)

H _H H _H H _H H H H H H H H H H H O H C O H C C H H OH OH H H H H H H H H H H H H H H H H H C C C C C C C C C C C C C C C _C Glycerol Fatty acid (palmitic acid) H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H HO O O O O C C C C _C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C _C C _C C _C C _C C _C C _C C C C O O

(a) Dehydration reaction in the synthesis of a fat

(29)

• Fatty acids vary in:

– length

– number

(30)

• _{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

(31)

• Unsaturated fatty acids

– Have one or more double bonds (causes “kink”)

– Are liquid at room temperatures. Why??

(b) Unsaturated fat and fatty acid

cis double bond causes bending

(32)

• Phospholipids

– Have only two fatty acids

– Have a phosphate group instead of a third

(33)

• Phospholipid structure

– Consists of a hydrophilic “head” and hydrophobic

“tails” CH2 O P O O O CH2 CH CH2 O O C O C O Phosphate Glycerol

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

Fatty acids (c) Phospholipid symbol Hydrophilic head Hydrophobic tails – CH2 +_N(CH _Choline 3)3

(34)

• The structure of phospholipids

– Results in a bilayer arrangement found in cell

membranes Hydrophilic head WATER WATER Hydrophobic tail

(35)

• Steroids

– Are lipids characterized by a carbon skeleton

(36)

• Cholesterol

– steroid found in cell membranes

– precursor for some hormones

HO CH₃ CH3 H₃C _CH 3 CH₃

(37)

• have many structures, resulting in a wide range

of functions

– Have many roles inside the cell

(38)

(39)

Animation: Structural Proteins Animation: Structural Proteins Animation: Storage Proteins Animation: Storage Proteins Animation: Transport Proteins Animation: Transport Proteins Animation: Receptor Proteins Animation: Receptor Proteins Animation: Contractile Proteins Animation: Contractile Proteins Animation: Defensive Proteins Animation: Defensive Proteins Animation: Hormonal Proteins Animation: Hormonal Proteins Animation: Sensory Proteins Animation: Sensory Proteins

Animation: Gene Regulatory Proteins Animation: Gene Regulatory Proteins

(40)

Polypeptides

• Polypeptides are polymers of amino acids

• _{A protein consists of one or more polypeptides}

– All proteins are polypeptides, but not all

(41)

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

(42)

Fig. 5-UN1

Amino

group

Carboxyl

group

 carbon

(asymmetric)

(43)

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)

(44)

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)

(45)

Acidic Arginine (Arg or R) Histidine (His or H) Aspartic acid (Asp or D) Glutamic acid (Glu or E) Lysine (Lys or K) Basic Electrically charged

(46)

Amino Acid Polymers

• Amino acids are linked by

peptide bonds

OH DESMOSOMES DESMOSOMES DESMOSOMES OH CH₂ C N H C H O H OH OH Peptide bond OH OH OH H H H H H H H H H H _H H N N N N N SH _chainsSide SH O O O O O H2O CH₂ CH₂ CH2 CH2 CH2 C C C C C C C C C C Peptide bond Amino end (N-terminus) Backbone (a) (b) Carboxyl end (C-terminus)

(47)

Protein Conformation and Function

• The

amino acid sequence

determines a

protein’s specific conformation (shape)

(48)

• The amino acid sequences of polypeptides

– Were first determined using chemical means

(49)

• Two models of protein conformation

(a) A ribbon model

(b) A space-filling model

Groove

(50)

• 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 H₂O Fructose 2 Active site

(51)

Four Levels of Protein Structure

• Primary structure

– unique amino acid

sequence in a polypeptide – Amino acid subunits +_H 3N Amino end o Carboxyl end o c

Gly ProThr Gly Thr Gly Glu Seu Lys Cys Pro Leu Met Val Lys Val Leu Asp Ala Val ArgGly

Ser Pro Ala Gly lle Ser ProPheHis_{Glu His}

Ala Glu Val Val Phe Thr Ala Asn Asp Ser

Gly ProArg ArgTyr Thrlle_Ala Ala Leu Leu Ser Pro Tyr Ser Tyr Ser Thr Thr Ala Val Val Thr Asn Pro LysGlu Thr Lys Ser Tyr Trp Lys Ala Leu

(52)

O C  helix  pleated sheet Amino acid subunits C N H C O C N H C O H R C N H C O H C R N H H R C O R C H N H C O _H N C O R C H N H H C R C O C O C N H H R C C O N H H C R C O N H R C H C O N H H C R C O N H R C H C O N H H C R C O N H H C R N H O O C _N C RC H O C H R N H O C R C H N H O C H C R N H C C N R H O C H C R N H O C R C H H C R N H C O C N H R C H C O N H C

• Secondary structure

– folding or coiling of the polypeptide into a repeating configuration

– includes the  helix and the  pleated sheet

(53)

• Tertiary structure

– overall three-dimensional shape of a polypeptide

– Results from interactions between amino acids and R

groups CH₂ CH O H O C HO CH₂ CH₂NH₃+-_O _C _CH 2 O CH2 S S CH2 CH CH3 CH3 H₃C H3C Hydrophobic interactions and van der Waals interactions Polypeptide backbone Hyrdogen bond Ionic bond CH₂ Disulfide bridge

(54)

• Quaternary structure

– overall protein structure that results from the

aggregation of two or more polypeptide subunits

Polypeptide chain Collagen  Chains  Chains Hemoglobin Iron Heme

(55)

• The four levels of protein structure

+_H 3N Amino end Amino acid subunits helix

(56)

Sickle-Cell Disease: A Simple Change in

Primary Structure

• Sickle-cell disease

– Results from a single amino acid

(57)

• Hemoglobin structure and sickle-cell disease

Fibers of abnormal hemoglobin

deform cell into sickle shape. Primary structure Secondary and tertiary structures Quaternary structure Function Red blood cell shape Hemoglobin A Molecules do not associate with one another, each carries oxygen.

Normal cells are full of individual hemoglobin molecules, each carrying oxygen     10 m 10 m     Primary structure Secondary and tertiary structures Quaternary structure Function Red blood cell shape Hemoglobin S Molecules interact with one another to crystallize into a fiber, capacity to carry oxygen is greatly reduced.  subunit  subunit 1 2 3 4 5 6 7 1 2 3 4 5 6 7

Normal hemoglobin Sickle-cell hemoglobin

. . .

. . . Exposed

hydrophobic region

(58)

What Determines Protein Conformation?

• Protein conformation depends on the physical

and chemical conditions

of the protein’s

(59)

• Denaturation

– when a protein unravels and loses its native

conformation

Denaturation

Renaturation

Denatured protein Normal protein

(60)

The Protein-Folding Problem

• Most proteins

– Probably go through several intermediate states on

their way to a stable conformation

(61)

• Chaperonins

– Are protein molecules that assist in the proper

folding of other proteins

Hollow cylinder Cap Chaperonin (fully assembled) Steps of Chaperonin Action: An unfolded poly-peptide enters the cylinder from one end.

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

The cap comes off, and the properly folded protein is released. Correctly folded protein Polypeptide 2 1 3

(62)

• X-ray crystallography

– Is used to determine a protein’s

three-dimensional structure _X-ray

diffraction pattern Photographic film Diffracted X-rays X-ray source X-ray beam

Crystal Nucleic acid Protein

(63)

Nucleic acids

• store and transmit hereditary information

• _{make up genes (units of inheritance)}

– program the amino acid sequence of

(64)

• There are two types of nucleic acids

– Deoxyribonucleic acid (DNA)

(65)

• DNA

– Stores information

for the synthesis of specific proteins – Directs RNA synthesis – Directs protein synthesis through RNA 1 2 3 Synthesis of mRNA in the nucleus

Movement of mRNA into cytoplasm via nuclear pore

Synthesis of protein NUCLEUS CYTOPLASM DNA mRNA Ribosome Amino acids Polypeptide mRNA

(66)

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’ end OH O O O O

(67)

• Each polynucleotide consists of monomers

called nucleotides

Nitrogenous base Nucleoside O O O  O P CH2 5’C 3’C Phosphate group Pentose sugar (b) Nucleotide O

(68)

• Nucleotide monomers are made up of

nucleosides

and phosphate groups

(c) Nucleoside components

CH CH

Uracil (in RNA) U

Ribose (in RNA) Nitrogenous bases Pyrimidines C N N C O H NH2 CH CH O CN H CH HN C O CCH3 N HN C C H O O Cytosine C

Thymine (in DNA) T N HC N C C N C CH N NH2 O N HC N H H C C N NH C NH2 Adenine A Guanine G Purines O HOCH2 H H H OH H O HOCH2 H H H OH H Pentose sugars

Deoxyribose (in DNA) Ribose (in RNA)

OH OH

CH CH

Uracil (in RNA) U 4’ 5” 3’ OH H2’ 1’ 5” 4’ 3’ 2’ 1’

(69)

• 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

Nitrogenous base Nucleoside O O O  O P CH₂ 5’C 3’C Phosphate group Pentose sugar (b) Nucleotide O

(70)

• The sequence of bases along a nucleotide

(71)

DNA Double Helix

• Cellular DNA molecules

– Have two polynucleotides that spiral around an

imaginary axis

(72)

• The DNA double helix

– Consists of two antiparallel nucleotide strands

3’ end

Sugar-phosphate backbone

Base pair (joined by hydrogen bonding) Old strands Nucleotide about to be added to a new strand A 3’ end 3’ end 5’ end New strands 3’ end 5’ end 5’ end

(73)

• The nitrogenous bases in DNA

– Form hydrogen bonds in a complementary fashion

(74)

The Theme of Emergent Properties in the

Chemistry of Life: A Review

• Higher levels of organization

– Result in the emergence of new properties