Chapter 5:

The Structure and Function

of Large Biological Molecules

AP Biology

Overview: The Molecules of Life

• Though there is an enormous diversity of molecules on Earth, the critically important

large molecules of all living things fall into just 4 main classes:

– 1) Carbohydrates

– 2) Lipids

– 3) Proteins

– 4) Nucleic Acids

• Within cells, small organic molecules are joined together to form larger molecules

– Members of these classes consist of 1000s of atoms and are thus called

macromolecules

• The architecture of these large biological molecules helps explain how they

work

– They exhibit unique emergent properties arising from the orderly arrangement

of their atoms

– This chapter considers how macromolecules are built, as well as examining the

structure and function of all 4 classes of large biological molecules

Concept 5.1: Macromolecules are polymers, built

from monomers

• The macromolecules in carbohydrates, proteins, and nucleic acids

are chain-like molecules called polymers

– Polys-many

– Meris-part

• POLYMER: long molecule consisting of many similar or

identical building blocks linked by covalent bonds (like a train

made up of many cars)

– The repeating units that are the building blocks of a polymer are

smaller molecules called MONOMERS

• Though the classes of polymers have different monomers, the chemical mechanisms

by which cells make and break down polymers are basically the same:

– Monomers are connected by covalently bonding to each other through loss of a

water molecules

• This type of reaction is called a CONDENSATION REACTION, or more

specifically, a DEHYDRATION REACTION (because a molecule of water

is lost)

– One of the monomers provides a hydroxyl group (-OH) and the other

provides a hydrogen (-H) to make up for the water molecule that is lost

• This reaction continues to

repeat, adding monomers to

the chain one by one,

forming a polymer

– Dehydration is sped up by enzymes

(specialized macromolecules that

speed up chemical reactions in cells)

The Synthesis of Polymers

• Polymers are broken down by HYDROLYSIS (reverse of dehydration; hydro = water,

lysis = break)

– Bonds between monomers are broken by

the addition of water molecules

• The hydrogen atom from water

attaches to one monomer

• The hydroxyl group (-OH) from water

attaches to adjacent monomer

– Example of hydrolysis: digestion

• Most of the organic material in food is in the form of polymers that must be

broken down because they are too large to enter our cells

• Released monomers are the absorbed into bloodstream for distribution to

all body cells

– Here, they can be reassembled (using dehydration reactions) into

new, different polymers that can perform specific function required by

those cells

The Breakdown of Polymers

Animation: Polymers

The Diversity of Polymers

• Each cell has 1000s of different kinds of macromolecules

– The types of macromolecules found in cells differ from cell to cell in the same

organism (depending on that cell’s functions and needs)

• Even more variety in types of macromolecules within cells is observed when

considering 2 different organisms of the same species

– Ex) Different DNA/proteins in humans lead to different characteristics

• Even greater variation is found between 2 different species

– Though all these different polymers are constructed from only 40-50 common

monomers (as well as some others that rarely occur), a huge variety of polymers exist

due to different arrangements of their monomers

• Like the alphabet: 26 letters can construct 100s of 1000s of words

– Despite this immense diversity of macromolecules, we can still group them roughly by

class based on molecular structure and function

2 3 HO H

Concept Check 5.1

• 1) What are the 4 main classes of large biological molecules?

• 2) How many molecules of water are needed to completely

hydrolyze a polymer that is 10 monomers long?

• 3) Suppose you eat a serving of green beans. What reactions

must occur for the amino acid monomers in the protein of the

beans to be converted to proteins in your body?

Concept 5.2: Carbohydrates serve as fuel and

building material

• Carbohydrates include both sugars and polymers of sugars

– The simplest carbohydrates are called monosaccharides

(or simple sugars)

• 2 monosaccharides can be joined to form double

sugars, or disaccharides

– Carbohydrates also include polysaccharides, polymers

composed of many sugar building blocks

Sugars

• Monosaccharides : monos = single; saccar = sugar

– Generally have molecular formulas that are some multiple of the unit

CH2O

• The most common monosaccharide is glucose (C6H12O6)

– Though it is convenient to draw glucose and other sugars with a linear

carbon skeleton, this representation is not completely accurate

• In aqueous solutions, most sugars form rings

• MONOSACCHARIDE FUNCTIONS:

– 1) Monosaccharides are major nutrients for cells

• Ex) During cellular respiration, cells extract energy from glucose

– 2) Carbon skeletons of sugars can also serve as raw material for

synthesis of other types of small organic molecules (amino acids, fatty

acids)

– 3) Sugar molecules not immediately used in these ways are usually

converted into disaccharides and polysaccharides

Functions of Monosaccharides

• Monosaccharides can be classified according to certain features:

– Carbonyl group

• Called aldoses (or aldehyde sugars)

if carbonyl group is at end of carbon

skeleton

– Ex) Glucose

• Called ketoses (or ketone sugars) is

carbonyl group is located within the

carbon skeleton

– Ex) Fructose – a structural

isomer of glucose

– Size of carbon skeleton

• Can range from 3-7 carbons long (hexoses, pentoses, trioses are most common)

– Spatial arrangement of their parts around asymmetric carbons (carbon attached to 4

different atoms)

• A disaccharide is formed when a dehydration reaction joins two monosaccharides

– This covalent bond is called a glycosidic linkage

• Examples of disaccharide synthesis

– a)Dehydration reaction in the synthesis of maltose

• Maltose is formed by linking 2 glucose monomers

– Also known as malt sugar, used in brewing beer

• The glycosidic linkage joins carbon 1 of one glucose to carbon 4 of the 2nd glucose

– If we joined the monomers in a different way, it would result in a different

disaccharide

• Examples of disaccharide synthesis (continued)

– b)Dehydration reaction in synthesis of sucrose

• Sucrose is considered table sugar

– It is composed of glucose and fructose monomers

• Plants usually transport carbohydrates from leaves to roots and to other

nonphotosynthetic organelles in this form

– Notice that fructose, though a hexose like glucose, forms a 5-sided ring

Animation: Disaccharides

Polysaccharides

• Polysaccharides are macromolecules – polymers with a few 100-1000

monosaccharides joined by glycosidic linkages

– Some polysaccharides are used for storage and then hydrolyzed

as needed to provide sugar for the cell

• Other polysaccharides serve as building material for

structures that protect cell or whole organism

– The structure and function of polysaccharides are determined by

their monomers as well as by positions of their glycosidic

linkages

Storage Polysaccharides

• Both plants and animals store sugars for later use in the form of storage polysaccharides

– PLANTS: store starch, a polymer of glucose molecules, as granules in plastids,

including chloroplasts

• Starch allows plant to stockpile surplus glucose that can later by broken down into

its individual monomers by hydrolysis to obtain energy

– ANIMALS: most animals also have enzymes that can hydrolyze plant starch to make

glucose available as a nutrient for cells

• Potatoes and grain (fruit of wheat, corn, rice, and other grasses) are the main

sources of starch in the human diet

• Animals store a polysaccharide called glycogen

– Hydrolysis of glycogen in liver and muscle cells releases glucose when

demand for sugar increases

– This stored fuel cannot sustain an animal for long (glycogen stores deplete in

~1 day in humans unless replenished by food consumption)

• Storage polysaccharides of plants and animals

– a) Most of the glucose monomers in starch

are joined by 1-4 linkages (carbon 1 and

carbon 4)

– The angle of these bonds makes

the polymer helical

• The simplest form of starch,

AMYLOSE, is unbranched

– Amylopectin, a more complex starch, is a branched polymer with 1-6

linkages at the branch points

• The light ovals in the micrograph are granules of starch within a chloroplast of a

plant cell

– b) Glycogen – an animal polysaccharide

• Glycogen is more branched than amylopectin

• Animals stockpile glycogen as dense clusters of granules within liver and muscle

cells (micrograph shows part of a liver cell)

• Mitochondria are organelles that help break down sugars – site of cell respiration

Structural Polysaccharides • Organisms use structural polysaccharides to build strong materials

– Ex) Cellulose is a polysaccharide that is the major component of cells walls in plants

– Like starch, cellulose is a polymer made up of glucose monomers

• The glycosidic linkages between theses 2 polymers are different, however,

because there are actually 2 slightly different ring structures for glucose

– When glucose forms a ring, the hydroxyl group attached to carbon 1 can be

positioned either above or below the plane of the ring,

– This results in an alpha ( ) (below) and beta ( ) (above) ring form for

glucose

Animation: Polysaccharides

• These different glycosidic linkages in starch and cellulose give these 2 molecules different 3-

D shapes

• Polymers with glucose are helical (starch)

• Polymers with glucose are straight (cellulose)

– This leaves some of the hydroxyl groups on the glucose monomers free to H-bond with

hydrogen atoms of other

cellulose molecules that lay

parallel to it

• Parallel cellulose molecules

held together in this way

are grouped into units

called microfibrils, which

form a strong building

material for plants

• Enzymes that digest starch by hydrolyzing alpha linkages are not able to hydrolyze beta

linkages in cellulose because of the different shapes of the 2 molecules

– Because humans do not posses enzymes to digest cellulose, any cellulose in our food

passes through the digestive tract and is eliminated with our feces

• Along the way, cellulose abrades the wall of the digestive tract, stimulating the

lining to secrete mucus (which aids in smooth passage of food through tract)

• Cellulose is thus an important part of a healthy diet in the form of fiber

– Some prokaryotes can digest cellulose, and many herbivores have symbiotic

relationships with these microbes

• Cows have some of the cellulose-

digesting microbes in their rumens

(1st compartment of stomach)

– These prokaryotes hydrolyze

cellulose in hay and grass and

convert the glucose into other nutrients for the cow

• Termites also have these prokaryotes living in their guts, allowing them to eat

wood

• Another important structural polysaccharide is chitin – a carbohydrate used by arthropods

(insects, spiders, crustaceans)

– It is used to build their exoskeletons, protecting the soft parts of these animals

• Pure chitin is leathery and flexible but it becomes hardened when encrusted with

calcium carbonate

– Chitin is also found in many fungi, which use this polysaccharide rather than cellulose

as the structural component of their cell walls

Concept Check 5.2

• 1) Write the formula for a monosaccharide that has 3

carbons.

• 2) A dehydration reaction joins 2 glucose molecules to

form maltose. The formula for glucose is C6H12O6.

What is the formula for maltose?

• 3) What would happen if a cow were given antibiotics

that killed all the prokaryotes in its stomach?

Concept 5.3: Lipids are a diverse group of

hydrophobic molecules

• Lipids are not true polymers and they are generally not big enough to

be called macromolecules

– They are grouped together because they all mix poorly, if at all,

with water due to their structure

• Although some may contain polar bonds associated with

oxygen, they consist mostly of hydrocarbon regions

– Lipids include fats, phospholipids, steroids, waxes, and certain

pigments

Fats

• Fats are large molecules assembled from a few smaller molecules by dehydration reactions,

mainly glycerol and fatty acids

– Glycerol is an alcohol with 3 carbons, each attached to a hydroxyl group

– A fatty acid is made up of a long carbon

skeleton, usually 16-18 carbons in

length

• The carbon at one end of the fatty acid

is part of a carboxyl group, giving this

group the name fatty “acid”

• The relatively nonpolar C-H bonds in the hydrocarbon chains are the reason they are

hydrophobic

– Fats separate from water because water

molecules H-bond to one another instead of

the fats

• To make a fat, 3 fatty acids each join to glycerol by

an ester linkage (bond between hydroxyl and

carbonyl group)

– The resulting fat is called a triaglycerol or

triglyceride

• Fatty acids making up a fat can be the

same or they can be 2 or 3 different kinds

• a) Dehydration reaction in the synthesis of a fat

– One water molecule is removed for each

fatty acid joined to the glycerol

• b) Triglycerol – a fat molecule

• Fatty acids vary in length and in the number and locations of double bonds

– Saturated fatty acids – do not contain any double bonds and so as many

hydrogen atoms as possible are bonded to carbon skeleton (“saturated” with

hydrogen)

– Unsaturated fatty acids – have one or more double

bonds, formed by the removal of hydrogen atoms from

the carbon skeleton

• As a result, the fatty acid will have a kink in its

hydrocarbon chain wherever a cis double bond

occurs

Animation: Fats

• Fats made from saturated fatty acids are called saturated fats

– Most animal fats are saturated

– Ex) Butter and lard

• Because the hydrocarbon chains of their

fatty acids (tails of the fat molecule) lack

double bonds, rotation about the C-H

bonds is permitted

– This flexibility allows the fat

molecules to pack tightly together,

making them solid at room

temperature

• Fats of plants and fish are generally unsaturated in contrast, and are therefore called

unsaturated fats

– Because they are usually liquid at room temperature,

they are referred to as oils (olive oil, cod oil)

• Kinks where cis double bonds are located prevent

the molecules from packing together closely

enough to solidify at room temperature

– Hydrogenated vegetable oils seen on food labels mean

that unsaturated fats have been synthetically converted

to saturated fats by adding hydrogen

– Ex) Peanut butter and margarine

• They are saturated to prevent their lipids from

separating out in liquid form

• Diets rich in saturated fats are one of many factors that contribute to cardiovascular

disease called atherosclerosis

– In this condition, deposits called plaques develop within the walls of blood

vessels

• This, in turn, causes inward bulges that impede blood flow and reduce the

resilience of vessels

– We have also recently discovered that the process of hydrogenating vegetable

oils produces not only saturated fats but also unsaturated fats with trans double

bonds (trans fats)

• These trans fats may contribute more than saturated fat to artherosclerosis

– Trans fats are common in baked goods and processed foods

• Despite their negative connotations, fats actually serve a very useful purpose

– The major function of fats is energy storage

• Hydrocarbon chains of fats are similar to gasoline molecules and just as rich in

energy

• A gram of fat actually stores 2X as much energy as a gram of a polysaccharide

(sugar)

– Because animals must carry their energy stores with them (unlike plants which are

immobile), the more compact structure of a fat is ideal

• Humans and other mammals stock their long-term food reserves in adipose cells

that swell and shrink as fat is deposited and withdrawn from storage

• Adipose tissue also cushions vital organs like kidneys and a layer of fat under the

skin insulates the body

– This subcutaneous layer is especially thick in many marine mammals

(whales, seals)

Phospholipids

• Another essential type of lipid is the phospholipid, which makes up cell membranes

– Phospholipids are similar to fat molecules but only have 2 fatty acids attached to

glycerol instead of 3

• The 3rd hydroxyl group of glycerol is joined instead to a phosphate group with a

negative charge

• Additional small molecules that are usually charged or polar can also be linked to

this phosphate group to form a variety of phospholipids

– The 2 ends of a phospholipid exhibit different behaviors toward water

• The hydrocarbon tails are

hydrophobic

• The phosphate group and its

attachments form a hydrophilic

head with an affinity for water

• When phospholipids are added to water, they self-assemble into double-layered

aggregations called bilayers that shield hydrophobic portions from water

– In the phospholipid bilayer of cell membrane, the hydrophilic heads are on the

outside of the bilayer and in contact with the aqueous interior and exterior of

the cell

– The hydrophobic tails point toward interior of bilayer, away from water

Steroids

• Another class of lipids are steroids – lipids whose carbon skeleton consists of 4 fused rings

– Different steroids have different chemical groups attached to their carbon skeleton rings

– They include many hormones, as well as cholesterol

• Cholesterol is a component of animal cell membranes and is also a precursor from

which other steroids are synthesized

– In vertebrates, cholesterol is made in the liver

– Many hormones (like vertebrate sex hormones) are steroids produced from

cholesterol

– Although cholesterol is an essential

molecule, a high level of it can

also contribute to artherosclerosis

Concept Check 5.3

• 1) Compare the structure of a fat (triglyceride) with

that of a phospholipid.

• 2) Why are human sex hormones considered

lipids?

• 3) Suppose a membrane surrounded an oil droplet,

as it does in the cells of plant seeds. Describe and

explain the form it might take.

Concept 5.4: Proteins have many structures,

resulting in a wide range of functions

• Proteins account for more than 50% of the dry mass of most cells

– They are instrumental in almost everything organisms do including:

• Speeding up chemical reactions

• Structural

support

• Storage

• Transport

• Cellular

communication

• Movement

• Defense against foreign substances

Animation: Structural Proteins

Animation: Storage Proteins

Animation: Transport Proteins

Animation: Receptor Proteins

Animation: Contractile Proteins

Animation: Defensive Proteins

Animation: Hormonal Proteins

Animation: Sensory Proteins

Animation: Gene Regulatory Proteins

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

• Most enzymes are proteins

– Enzymes regulate metabolism by acting as catalysts

• Catalysts are chemical agents that selectively speed up chemical reactions without

being consumed by the reaction

• They can be thought of as workhorses that keep cells running by carrying out

processes of life because they can perform their functions again and again (they

are not consumed)

– Ex) The enzyme sucrase accelerates hydrolysis of sucrose into glucose and fructose

• Note that the sucrase is not consumed curing the reaction but remains available for

further catalysis

– 1)Active site is available for a molecule of substrate – the reactant on which

the enzyme acts

– 2)Substrate binds to enzyme

– 3)Substrate is converted to products

– 4)Products are released

Animation: Enzymes

Polypeptides

• Humans have 10s of 1000s of different proteins each with a specific

structure and function

– Despite their diversity, all proteins are made up of one or more

polymers constructed from the same set of 20 amino acids

• These polymers of amino acids are called polypeptides

– Each protein is folded and coiled into a specific 3-dimensional

structure

Amino Acid Monomers

• Amino acids are organic molecules that have carboxyl and amino groups

– All amino acids share a common structure

• They differ only in a variable group R group (also called a side chain)

– The general formula for an amino acid is shown below

• At the center of each amino acid is an asymmetric carbon atom – called an alpha

carbon – which has 4 different partners:

– Carboxyl group

– Amino group

– Hydrogen atom

– Variable R group

• 20 different amino acids are used by cells to build their proteins (organisms do have

other amino acids that are occasionally found in proteins but they are relatively rare)

– Amino acids here are shown in their prevailing

ionic forms at pH 7.2, the pH of the cell

– The 3 letter and more commonly used

one-letter abbreviations for these amino acids

are also shown

– All amino acids used in proteins are the same

enantiomer, called the L form (as

shown here)

• Amino acids can be grouped according to the properties of their side chains (highlighted in

white)

– Nonpolar amino acids – hydrophobic

– Polar amino acids – hydrophilic

– Acidic amino acids – side chains are generally

negative due to presence of a carboxyl group

which usually dissociates (ionizes) at

cellular pH

– Basic amino acids – have amino groups in

their side chains and are generally positive

in charge

• Because they are charged, acidic and basic

amino acids are also hydrophilic

• ***Note: All amino acids have a carboxyl

group and an amino group – the terms

acidic and basic in this context refer only

to groups on side chains

Amino Acid Polymers

• Amino acids are linked together to form polymers using covalent peptide bonds

– They become joined by a dehydration reaction when 2 amino acids are positioned so

that the carboxyl group of one amino acid is next to the amino group of the other

• This process is repeated over and over and results in a polypeptide

– At one end of resulting polypeptide chain is a free amino group and is therefore called

the N-terminus

• The opposite end is a free carboxyl group and

is called the C-terminus

– Polypeptides vary in length from a few monomers to

1000s

• Each has a specific sequence of amino acids,

using a limited set of monomers to make many

different combinations

Protein Structure and Function

• The activities of proteins are due to their 3-dimensional structure

– The simplest level of structure is a protein’s amino acid sequence

• Note: The term polypeptide is not synonymous with the word protein (Just as a long

strand of yarn and a sweater of a particular shape and size are not the same)

– A functional protein is not JUST a polypeptide chain, but one or more

polypeptides precisely twisted, folded, and coiled into a molecule of unique

shape

– The amino acid sequence of each polypeptide does, however, determine what

3-dimensional structure the protein will have

• Lysozyme is an enzyme present in sweat, tears, and saliva

– It helps prevent infection by binding to and destroying specific molecules on the

surface of many kinds of bacteria

• A) A ribbon model shows how the single polypeptide chain folds and coils to form the

functional protein

– Yellow lines represent cross-linking bonds between cysteines that stabilize the protein‟s

shape

• B) A space-filling model shows the globular shape seen in many proteins more clearly

– The groove is the part of the protein

that recognizes and bonds

the target molecules on

bacterial walls

• When a cell makes a polypeptide, the chain usually forms spontaneously and is

driven and reinforced by formation of different bonds between parts of the chain

• This in turn, depends on the sequence of amino acids

– Many proteins are roughly spherical – called globular proteins

• Others are shaped like long fibers – called fibrous proteins

– A protein‟s specific structure determines how it works

• Functions of proteins in most cases

depend on their ability to recognize

and bind to some other molecule

• This fit is very specific, like a lock and

key

– Ex) Lysozyme (previous)

– Ex) Virus and antibody (right)

Four Levels of Protein Structure

• All proteins share 3 superimposed levels of structure

– Primary: sequence of amino acids

– Secondary: consists of coils and folds in polypeptide chain

– Tertiary: determined by interactions amoung R groups

– Quaternary : a 4th level that arises when a protein consists

of 2 or more polypeptide chains

Animation: Protein Structure Introduction

Primary Structure

• Primary Structure – a protein‟s unique sequence of amino acids

– This is comparable to the order of letters in a very long word

– To figure out how many different way there are to arrange a

particular sequence of amino acids:

20 ^ (# of AA in protein)

– The precise primary structure of a protein is not determined at

random but by inherited genetic information

Animation: Primary Protein Structure

Secondary Structure

• A protein‟s secondary structure results from coiling and folding of segments of their

polypeptide chains

– This folding and coiling is the result of H-bonds between repeating parts of

polypeptide backbone (not the amino acid side chains)

• Any oxygen and nitrogen atoms of the backbone are electronegative (have

partial negative charges),

– Thus, the weakly positive hydrogen atom attached to a nitrogen atom

has an affinity for the oxygen atom of a nearby peptide bond

• Individually, these H-bonds are weak,

– Because they are repeated many times over a large portion of the

polypeptide chain, however, they can support a protein‟s particular

shape

Animation: Secondary Protein Structure

Common Secondary Structure: Alpha Helix

• Some common secondary structures:

– 1) Alpha helix – coil held together by H-bonding between every 4th amino acid

• Some proteins may have only a single stretch of an alpha helix (ex:

transthyretin)

• Others have multiple

stretches of these helices

separated by nonhelical

regions

• Still others (ex: alpha-

keratin, the structural

component of hair) have alpha helix formation over most of their length

Common Secondary Structure: Beta Pleated Sheet

• Some common secondary structures:

– 2) Beta pleated sheet – 2 or more regions of

polypeptide chain lying side by side are connected by

H-bonds between parts of the 2 parallel polypeptide

backbones

• Pleated sheets make up the core of many

globular proteins (like transthyretin)

• They also make up large portions

of many fibrous proteins

(including silk proteins of

spider webs)

Animation: Secondary Protein Structure

Tertiary Structure

• The tertiary structure of a protein is superimposed on the

patterns of secondary structure

– This level gives the overall shape of the polypeptide

• It is due to interactions between side chains (R groups)

of various amino acids (not between interactions of

backbone like in secondary structure)

Animation: Tertiary Protein Structure

Tertiary Structure: Interactions • Types of Interactions Contributing to Tertiary Structure:

– 1) Hydrophobic interaction – as polypeptide folds into its functional shape,

amino acids with hydrophobic (nonpolar) side chains usually end up in clusters

at core of protein, out of contact with water

• Once nonpolar amino acid side chains are close together, van der Waals

interactions help hold them together

• At the same time, H-bonds between polar side chains and ionic bonds

between positively and negatively

charged side chains also help stabilize

tertiary structure

– 2) Disulfide bridges – covalent bonds

between sulfur atoms that form when

2 cysteine monomers (AAs containing

sulfhydyl groups –SH) are brought close

together by folding of protein

• Bonds 2 parts of a protein together

Quaternary Structure • When proteins consist of 2 or more polypeptide chains, a 4th level of organization is

required

– Quaternary structure is the overall protein structure

that results from the aggregation of these

polypeptide subunits

• Examples of quaternary structure include:

– 1) Collagen: a fibrous protein consisting of 3

polypeptides coiled like a rope

• Collagen supports connective tissue in the skin, bone, tendons, ligaments,

and other body parts

• It makes up 40% of all proteins in the human body

– 2) Hemoglobin: a globular protein consisting of 4 polypeptides: 2 alpha and 2

beta chains

• Hemoglobin is the oxygen-binding

protein of red blood cells

Animation: Quaternary Protein Structure

• Figure 5.21 Levels of protein structure

– Ex) Transthyretin – globular protein found in blood that transports

vitamin A and one of the thyroid hormones throughout the body

• Made of 4 identical polypeptide chains totaling 127 amino acids

• 20^127 possible sequences

Sickle-Cell Disease: A Change in Primary Structure

• Even a slight change in primary structure can affect a protein‟s shape and function

– Ex) Sickle Cell Anemia: an inherited blood disorder

• It is caused by substitution of one amino acid (valine) for the normal amino

acid (glutamic acid) in the primary structure of hemoglobin

– Recall: hemoglobin is the protein that carries oxygen in RBCs

– Normal RBC are disk-shaped

• In sickle cell disease, the

abnormal hemoglobin

molecules tend to crystallize,

deforming some of the cells

into a sickle shape

• These angular cells clog tiny

blood vessels and impede

blood flow

– This results in a reduced

capacity to carry oxygen

What Determines Protein Structure?

• In additional to the levels of protein structure already discussed, a protein‟s shape

can also be influenced by the physical and chemical conditions of the protein‟s

environment

– Changes in any of the following conditions can cause a protein to unravel and

lose its native shape, a process called denaturation

• pH

• Salt concentration

• Temperature

• Other environmental factors

– Because a protein‟s shape is essential to its function, denatured proteins are

biologically inactive

What Determines Protein Structure?

• Proteins can become denatured if:

– They are transferred from an aqueous environment to organic solvent (ex:

ether, chloroform)

• The polypeptide chain refolds so hydrophobic regions face outside toward

solvent

– They are exposed to chemicals that disrupt H-bonds, ionic bonds, and disulfide

bridges

– They are excessively heated

• Heat agitates the polypeptide chain enough to overpower the weak

interaction that stabilize protein structure

– Ex) egg whites becomes opaque during cooking because denatured

proteins are insoluble and solidify

Renaturation of Proteins

• High temperature or various chemical treatment will denature a protein, causing it to

lose its shape and hence its ability to function

– If denatured protein remains dissolved, it can often renature when the chemical

and physical aspects of its environment are restored to normal

– We can therefore conclude that the information for building a specific shape is

intrinsic in protein‟s primary structure – its sequence of amino acids will

determine protein‟s shape

Protein Folding in the Cell

• Most proteins probably go through several intermediate structures on their way to a

stable shape

– In the crowded environment of the cell, there are specific proteins that aid in the

folding of other proteins

• These protein molecules that assist in proper folding of other proteins are

called chaperonins (or chaperone proteins)

• Chaperonins do not specify final protein structure, but they keep the

polypeptides segregated from “bad” influences in the cytoplasm while it

folds spontaneously

– Misfolding of proteins is a serious problem

• Alzheimer‟s and Parkinson‟s are associated with an accumulation of

misfolded proteins

• This computer graphic below shows a large chaperonin-protein complex

– It has an interior space that provides a shelter for the proper folding of newly

made polypeptides

– The complex consists of 2 proteins:

• 1) One protein is a hollow cylinder

• 2) The other is a cap that can fit on either end

• Steps of Chaperonin Action:

– 1)An unfolded polypeptide enters cylinder from one end

– 2)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

– 3)The cap

comes off and

the properly folded

protein is released

• Determining the exact 3-dimensional structure of a protein is not

simple because a single protein molecule is made up of 1000s of

atoms

– One method scientists have used to work out the 3D structures

for proteins such as hemoglobin (1959) is X-ray

crystallography

– Another method is nuclear magnetic resonance (NMR) which

does not require protein crystallization

– A more recent approach uses bioinformatics to predict the 3-D

structures of polypeptides from their amino acid sequences

• What can the 3-D shape of the enzyme RNA polymerase II tell us about its function?

– Experiment: Roger Kornberg used X-ray crystallography to determine the

shape of RNA polymerase II, which binds to the DNA double helix and makes

RNA

• After crystallizing a complex of all 3 components (DNA, RNA, RNA

polymerase), an X-ray beam was aimed through the crystal

• Atoms that the crystal diffracted (bent) the X-rays into an orderly array that

a digital detector recorded as a pattern of spots called an X-ray diffraction

pattern

– Results: Using the x-ray diffraction patterns

and amino acid sequences already

determined by chemical methods, Kornberg

built a 3-D model of the complex with the

help of computer software (see picture)

– Conclusion: By analyzing the model,

researchers developed a hypothesis about

the functions of different regions of RNA polymerase

II (such as region above DNA may act as a

clamp that holds nucleic acids in place

during transcription)

Concept Check 5.4

• 1) Why does a denatured protein no longer

function normally?

• 2) What parts of a polypeptide chain participate in

the bonds that hold together secondary structure?

What parts participate in tertiary structure?

• 3) If a genetic mutation changes primary structure,

how might it destroy the protein‟s function?

Concept 5.5: Nucleic acids store and transmit

hereditary information

• The amino acid sequence of a polypeptide is

programmed by a unit of inheritance called a gene

– Genes are made of DNA, a polymer belonging to a

class of compounds called nucleic acid

The Roles of Nucleic Acids

• There are 2 types of nucleic acids: DNA (deoxyribonucleic acid) and RNA

(ribonucleic acid)

• These nucleic aids allow living organisms to reproduce from one

generation to the next

– Unlike other molecules, DNA provides directions for its own replication

• DNA also directs RNA synthesis (transcription) and, using RNA as

an intermediate, controls protein synthesis (translation)

• The sites of protein synthesis are tiny structures called ribosomes,

found in the cytoplasm of the cell

• Figure 5.26: DNA → RNA → protein

– Each gene along a DNA molecule directs the synthesis of a type of RNA

molecule called messenger RNA (mRNA)

• This process is called

transcription

– mRNA then directs the production

of a polypeptide, which then folds

into a protein

• This process is called translation

– We can summarize the flow of

genetic information as:

DNA – RNA – Protein

The Structure of Nucleic Acids

• Nucleic acids exist as polymers called polynucleotides

– Each polynucleotide is made up of monomers called nucleotides

• A nucleotide is composed of 3 parts:

– Nitrogenous base

– 5-carbon sugar (pentose)

– Phosphate group

– The portion of a nucleotide without the phosphate group is called a

nucleoside

• a) A polynucleotide has a sugar phosphate backbone with different attachments, the

nitrogen bases

• b) A nucleotide monomer includes a nitrogenous base, a sugar, and a phosphate

group

– Without the phosphate group, the structure is called a nucleoside

• c) A nucleoside includes a nitrogenous base (purine or pyrimidine) and a 5-carbon

sugar (deoxyribose or ribose)

– ***Because the

atoms in both the

nitrogenous base

and the sugar are

numbered, the

sugar atoms have

a prime („) after the

number to

distinguish them

Nucleotide Monomers

• There are 2 families of nitrogenous bases:

– Pyrimidines: 6-membered ring of carbon and nitrogen atoms

• Members of the pyrimidine family are cytosine (C), thymine (T), and uracil

(U)

– Purines: 6-membered ring fused to a 5-membered ring

• Include adenine (A) and guanine (G)

– Specific pyrimidines and purines differ only in the chemical groups attached to

the rings

• The nitrogen atoms tend to take up H+ ions from solution, which is why they are

called nitrogenous BASES

Nucleotide Monomers

• A, G, and C are found in both DNA and RNA

– Thymine is found only in DNA

– Uracil is found only in RNA

• The sugar connected to the nitrogenous base differs depending on the

nucleic acid:

– Ribose in RNA

– Deoxyribose in DNA

• The only difference between the 2 sugars is that deoxyribose lacks

an oxygen atom on the 2nd carbon in the ring (hence

DEOXYribose)

Nucleotide Polymers

• Adjacent nucleotides are joined by a phosphodiester linkage to build

polynucleotides

– This consists of a phosphate group that links the sugars of the 2 nucleotides

• Adjacent nucleotides are joined by covalent bonds that form between the

–OH group on the carbon of one nucleotide and the phosphate of the next

carbon

• This bonding

results in a

backbone with a

repeating pattern

of sugar-

phosphate units

• The 2 free ends are distinctly different from each other

– One end has a phosphate attached to a 5‟ carbon

– Other end has a hydroxyl group on the 3‟ carbon

• We refer to these as 5‟ and 3‟ ends, respectively

– We can say that DNA has a built-in directionality along its sugar-phosphate

backbone, from 5‟ to 3‟

• The sequence of bases along DNA or mRNA is different for each gene

– A gene‟s meaning to the cell is

thus encoded in this specific

sequence of the four bases of

DNA and mRNA

– The linear order of bases in a

gene specifies the amino acid

sequence (primary structure) of

a protein, which in turn

specifies the protein‟s 3-D

structure and function

The DNA Double Helix

• DNA molecules consist of 2 polynucleotides that spiral around an imaginary axis,

forming a double helix

– The 2 sugar-phosphate backbones run in opposite 5‟ to 3‟ directions from each

other,

• This arrangement is referred to as antiparallel (like a divided highway)

– The sugar phosphate backbones are on the outside of the helix and nitrogen

bases are paired in the interior of the helix

• The 2 strands of polynucleotides are

held together by H-bonds between the

paired bases and by van der Waals

interactions between stacked bases

– Most DNA molecules are very long , made

of 1000s to millions of base pairs and

many genes

The DNA Double Helix

• Only certain bases in the double helix are compatible with each other

– A always pairs with T

– G always pairs with C

• The 2 strands are thus complementary

to each other, each a predictable

counterpart of the other

• In preparation for cell division, the 2 strands of the DNA

molecule separate and both serve as a template to

order nucleotides into a new complementary strand

– The result is 2 identical copies of the

original double-stranded DNA

molecule, which are then

distributed to the 2 daughter cells

DNA and Proteins as Tape Measures of Evolution

• Genes and their proteins document the hereditary background of an organism

– The linear sequences of nucleotides in DNA are passed from parent to

offspring

• Siblings have a greater similarity in DNA and proteins than do unrelated

individuals of the same species

– This concept of molecular “geneology” also extends to relationships between

species

• 2 species that are closely related share a greater proportion of their DNA

and protein sequences than more distantly related species

– Ex) Comparison of polypeptide chain of human hemoglobin with 5

other vertebrates:

• Out of 146 amino acids, humans and gorillas differ only by 1

amino acid

• Humans and frogs differ in 67 amino acids

Concept Check 5.5

• 1) Go to Figure 5.27a (pp. 87) and number all the carbons in the sugars for the top 3

nucleotides; circle the nitrogenous bases and star the phosphates.

• 2) In a DNA double helix, a region along one DNA strand has this sequence of

nitrogenous bases: 5‟-TAGGCCT-3‟. Write down this strand and its complementary

strand, clearly indicating the 5‟ and 3‟ ends of the complementary strand.

• 3) (a) Suppose a substitution occurred in one DNA strand of the double helix in

question 2, resulting in:

5‟-TAAGCCT-3‟

3‟-ATCCGGA-3‟

Draw the 2 strands; circle and label the mismatched bases

(b) If the modified top strand is replicated, what would be its matching stand be?

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

• Life is organized along a hierarchy of structural levels

– With each increasing level of order, new properties

emerge

– In the next unit, we will study the next level of

organization, cell structure and function

Fig. 5-UN2a

Fig. 5-UN2b

You should now be able to:

1. List and describe the four major classes of

molecules

2. Describe the formation of a glycosidic linkage

and distinguish between monosaccharides,

disaccharides, and polysaccharides

3. Distinguish between saturated and

unsaturated fats and between cis and trans fat

molecules

4. Describe the four levels of protein structure

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

You should now be able to:

5. Distinguish between the following pairs:

pyrimidine and purine, nucleotide and

nucleoside, ribose and deoxyribose, the 5

end and 3 end of a nucleotide

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