Learning Objectives 1. Compile your own glossary from the KEY WORDS

displayed in bold type in the learning objectives below.

The Chemical Nature of Cells (page 16-36) 2. Recall the structures and organelles found in a typical

eukaryotic cell. Identify common elements found in organisms and their role in cells. Relate the structure and properties of water to its role in biological systems. Describe the biological role of inorganic ions.

3. Describe the basic composition, general formula, and biological roles of carbohydrates.

4. Describe examples of monosaccharides. With reference to glucose, explain the biological significance of isomerism in monosaccharides.

5. Describe examples of disaccharides and their functions. Explain how disaccharides are formed by condensation and broken apart by hydrolysis.

6. Describe the structure and formation of some named polysaccharides (e.g. starch, glycogen, and cellulose), and relate their structure to their biological function.

7. Describe the properties of lipids, and their diversity and roles in biological systems. Include reference to phospholipids, steroids, waxes, and triglycerides.

8. Describe the structure of triglycerides and their formation by condensation. Distinguish between saturated and unsaturated fatty acids and relate this difference to the properties of the fat or oil that results.

9. Describe the structure of a phospholipid and explain how this is important to their role in membranes.

10. Describe examples of nucleic acids and their roles in biological systems. Describe the components of a nucleotide. Compare the structure and function of DNA and RNA. Understand the role of condensation reactions in the formation of nucleic acids.

11. Describe the structure and general formula of amino acids. Explain the basis for the different properties of amino acids. Describe how amino acids are joined by condensation to form polypeptides and how polypeptides are broken down by hydrolysis.

12. Identify where in the cell proteins are made. Explain what is meant by the proteome and describe the structure and functional diversity of proteins including:

•Primary and secondary structure •Tertiary structure and its relationship to function •Quaternary structure (if applicable), how this arises,

and how it relates to biological function. •Classificationsofproteinsbasedonstructure(e.g.

globular or fibrous) or function (e.g. catalytic).

13. Explain how denaturation destroys protein activity.

14. Describe how proteins are modified after production to produce glycoproteins or lipoproteins. Describe some of the roles of these modified proteins in the cell.

15. Describe the role of organelles in packaging and transport of macromolecules. Describe the steps involved in producing a macromolecule for secretion.

Enzymes and Metabolism (pages 37-42) 16. Explain how enzymes regulate metabolic pathways.

Using an example, e.g. PKU or albinism, explain how enzyme malfunction results in a metabolic disorder.

17. Explain how enzymes work as biological catalysts to bring about reactions in cells. Include reference to the activation energy, active site, enzyme-substrate complex. Distinguish between the induced fit and the lock and key models of enzyme function.

18. Describe how enzyme activity is affected by: (a) Coenzymes and cofactors

(b) Competitive and non-competitive inhibitors (c) pH and temperature (d) Substrate concentration and enzyme concentration

HSC VCE QLD SA WA

The Chemistry of Life

Complete:

1, 16-18

Complete:

1-18Some numbers

extension as required

Complete:

1-18Some numbers

extension as required

Complete:

1-18Some numbers

extension as required

Complete:

1, 10, 16-18

See the ‘Textbook Reference Grid’ on page 7 for textbook page references relating to material in this topic.

Supplementary TextsSee pages 5-6 for additional details of these texts:■ Adds, J. et al., 2003. Molecules and Cells.

■ Harwood, R., 2002. Biochemistry.

■ Kennedy, E. 2005. Biochemistry Option.

See page 6 for details of publishers of periodicals:

■ Smart Proteins New Scientist, 17 March 2001 (Inside Science). The structure and role of proteins.

■ Glucose & Glucose-Containing Carbohydrates Biol. Sci. Rev., 19(1) Sept. 2006, pp. 12-15. The structure of glucose and its polymers.

■ Designer Starches Biol. Sci. Rev., 19(3) Feb. 2007, pp. 18-20. Properties and functions of starch.

■ Exploring Proteins Biol. Sci. Rev., 16(4) April 2004, pp. 32-36. Understanding how proteins function as complexes within the cell.

■ Making Proteins Work (I) Biol. Sci. Rev., 15(1) Sept. 2002, pp. 22-25. A synopsis of how a globular and a fibrous protein each become functional.

■ Making Proteins Work (II) Biol. Sci. Rev., 15(2) Nov. 2002, pp. 24-27. How carbohydrates are added to proteins to make them functional.

■ Enzymes Biol. Sci. Rev., 15(1) Sept. 2002, pp. 2-5. Enzymes as catalysts: how they work, models of enzyme function, and cofactors and inhibitors.

See pages 8-9 for details of how to access Bio Links from our web site: www.biozone.com.au From Bio Links, access sites under the topics:CELL BIOLOGY AND BIOCHEMISTRY > Biochemistry & Metabolic Pathways:•Enzymes •Energyandenzymes•TheBiologyProject:Biochemistry •Energy,enzymesandcatalysisproblem set •Reactionsandenzymes

Presentation MEDIA:

CELL BIO & BIOCHEM:

• Molecules of Life

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Related activities: Organic Molecules, Carbohydrates, Lipids, Proteins, Nucleic Acids Web links: Structure of WaterA 2

Water moleculeFormula: H2O

Water surroundinga positive ion (Na+)

Water surroundinga negative ion (Cl-)

Oxygen is attracted to the Na+ Hydrogen is attracted to the Cl-

Small -vecharge

Small +vecharge

HO

H

Water is a dipolar molecule. It is a good solventbecause its molecules form a layer around moleculesand ions (right). Water is a liquid at room temperatureand it is a medium inside cells and for aquatic life.

Lipids provide insulation and aconcentrated source of energy.Phospholipids are a major componentof cellular membranes, including themembranes of organelles.

Nucleotides and nucleic acidsNucleic acids encode informationfor the construction andfunctioning of an organism. Thenucleotide, ATP, is the energycurrency of the cell.

Proteins may be structural (e.g. collagen inskin, proteins in ribosomes), catalytic(enzymes), or they may be involved inmovement, message signalling, internaldefence and transport, or storage.

Water is a major component of cells: manysubstances dissolve in it, metabolic reactionsoccur in it, and it provides support and turgor.

Carbohydrates form thestructural components of cells,e.g. cellulose cell walls (arrowed),they are important in energystorage, and they are involved incellular recognition.

Ribosomes intranslation

Thylakoid sacsof a chloroplast

Chromosome

The Biochemical Nature of the CellThe molecules that make up living things can be grouped into five broad classes: carbohydrates, lipids, proteins, nucleic acids, and water. Water is the main component of organisms and provides an environment in which metabolic reactions can occur. An important feature of water is its dipole nature. Water molecules attract each other, forming large numbers of hydrogen bonds. It is this feature that gives water many of its unique properties, including its low viscosity and its chemical behaviour as a

universal solvent. Apart from water, most other substances in cells are compounds of carbon, hydrogen, oxygen, and nitrogen. These elements form strong, stable covalent bonds by sharing electrons. The combination of carbon atoms with the atoms of other elements provides a huge variety of molecular structures. Many of these biological molecules, e.g. DNA, are very large and contain millions of atoms. The role of these molecules in the cells is outlined below.

1. Explain the importance of the molecular structure of water to life on Earth:

2. Summarise the biological role of each of the following biological molecules:

(a) Carbohydrates:

(b) Lipids:

(c) Proteins: (d) Nucleic acids:

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The Chem

istry of Life

Related activities: Biochemical Nature of the Cell, Amino Acids, Proteins, Water and Inorganic Ions A 1

Organic MoleculesOrganic molecules are those chemical compounds containing carbon that are found in living things. Specific groups of atoms, called functional groups, attach to a carbon-hydrogen core and confer specific chemical properties on the molecule. Some organic molecules in organisms are small and simple, containing only one or a few functional groups, while others are large complex assemblies called macromolecules. The macromolecules that make up living things can be grouped into four classes: carbohydrates, lipids, proteins, and nucleic acids. An understanding of the structure and function of these

molecules is necessary to many branches of biology, especially biochemistry, physiology, and molecular genetics. The diagram below illustrates some of the common ways in which biological molecules are portrayed. Note that the molecular formula expresses the number of atoms in a molecule, but does not convey its structure; this is indicated by the structural formula. Molecules can also be represented as models. A ball and stick model shows the arrangement and type of bonds while a space filling model gives a more realistic appearance of a molecule, showing how close the atoms really are.

1. Identify the three main elements comprising the structure of organic molecules:

2. Name two other elements that are also frequently part of organic molecules:

3. State how many covalent bonds a carbon atom can form with neighbouring atoms:

4. Distinguish between molecular and structural formulae for a given molecule:

5. Describe what is meant by a functional group:

6. Classify formaldehyde according to the position of the C=O group:

7. Identify a functional group always present in amino acids:

8. Identify the significance of cysteine in its formation of disulfide bonds:

Portraying Biological Molecules

CH2OH

C

H

OH

C

C

C

C

OH

H OH

HOH

H

HO

23

4

5

6

1

Structural formulaα glucose (ring form)

Space filling modelβ-D-glucose

Ball and stick modelGlucose

23

45

6

1

C1

C2

C3

C4

C5

C6

H

OH

OH

OH

H

OH

H

H

H

HO

H

H O

Structural formulaGlucose (straight form)

Molecularformula

C6H12O6

The numbers next tothe carbon atoms areused for identificationwhen the moleculechanges shape

Glucose

Carbon

Hydrogen

Nitrogen

Oxygen

Sulfur

Key to SymbolsBiological molecules may also includeatoms other than carbon, oxygen, andhydrogen atoms. Nitrogen and sulfurare components of molecules such asamino acids and nucleotides. Somemolecules contain the C=O (carbonyl)group. If this group is joined to at leastone hydrogen atom it forms analdehyde. If it is located between twocarbon atoms, it forms a ketone.

Acetate Formaldehyde Cysteine

H3C CO

OH2N C

H

ONH2

COH

OCCHS

HH

H

COH

OCarboxyl

CH

OAldehydeKetone

CO

CC

Examples of Biological Molecules

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Related activities: Biochemical Nature of the Cell, Organic MoleculesWeb links: Hydrogen Bonds and Water, Water and pHRA 2

1. On the diagram above, showing a positive and a negative ion surrounded by water molecules, draw the positive and negative charges on the water molecules (as shown in the example provided).

2. Explain the importance of the dipole nature of water molecules to the chemistry of life:

3. Distinguish between inorganic and organic compounds:

4. Describe a role of the following elements in living organisms (plants, animals and prokaryotes) and a consequence of the element being deficient in an organism's diet:

(a) Calcium:

(b) Iron:

(c) Phosphorus:

(d) Sodium:

(e) Sulfur:

(f) Nitrogen:

Water and Inorganic IonsThe Earth's crust contains approximately 100 elements but only 16 are essential for life (see the table of inorganic ions below). Of the smaller molecules making up living things water is the most abundant typically making up about two-thirds of any organism's

body. Water has a simple molecular structure and the molecule is very polar, with ends that exhibit partial positive and negative charges. Water molecules have a weak attraction for each other and inorganic ions, forming weak hydrogen bonds.

Water provides an environment inwhich metabolic reactions can happen.Water takes part in, and is a commonproduct of, many reactions. The mostimportant feature of the chemicalbehaviour of water is its dipole nature.It has a small positive charge on eachof the two hydrogens and a smallnegative charge on the oxygen. Water molecule

Formula: H2OWater surroundinga positive ion (Na+)

Water surroundinga negative ion (Cl-)

Oxygen isattracted tothe Na+

Hydrogenis attractedto the Cl-

Small -vecharge

Small +vechargesH

OH

Inorganic ions are important for thestructure and metabolism of all livingorganisms. An ion is simply an atom(or group of atoms) that has gained orlost one or more electrons. Many ofthese ions are soluble in water. Someof the inorganic ions required byorganisms and their biological rolesare listed in the table on the right.

Water and Inorganic Ions

Component of bones and teethCalciumCa 2+

Component of chlorophyllMagnesiumMg 2+

Component of hemoglobinIron (II)Fe 2+

Component of amino acidsNitrateNO3 -

Component of nucleotidesPhosphatePO4 3-

Involved in the transmission of nerve impulsesSodiumNa +

Involved in controlling plant water balancePotassiumK +

Involved in the removal of water from urineChlorideCl -

Name Biological roleIon

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The Chem

istry of Life

Related activities: Organic MoleculesWeb links: Biomolecules: Carbohydrates, Condensation and Hydrolysis A 2

Carbohydrates

WM

U

Skeletal muscle tissue

BF

Starch granules in a plant cell

Starchgranules

Chitinous insect exoskeleton

BF

Cellulose

O

O

6

O

6

NHCOCH3 6

NHCOCH3

NHCOCH3

Symbolic form of cellulose

1, 4 glycosidic bondscreate unbranched chains

Symbolic form of chitin

Symbolic formof glycogen

MonosaccharidesMonosaccharides are used as a primary energy source for fuellingcell metabolism. They are single-sugar molecules and include glucose(grape sugar and blood sugar) and fructose (honey and fruit juices).The commonly occurring monosaccharides contain between threeand seven carbon atoms in their carbon chains and, of these, the 6Chexose sugars occur most frequently. All monosaccharides are classifiedas reducing sugars (i.e. they can participate in reduction reactions).

DisaccharidesDisaccharides are double-sugar molecules and are used as energysources and as building blocks for larger molecules. The type ofdisaccharide formed depends on the monomers involved and whetherthey are in their α- or β- form. Only a few disaccharides (e.g. lactose)are classified as reducing sugars.

Sucrose = α-glucose + β-fructose (simple sugar found in plant sap)Maltose = α-glucose + α-glucose (a product of starch hydrolysis)Lactose = β-glucose + β-galactose (milk sugar)Cellobiose = β-glucose + β-glucose (from cellulose hydrolysis)Single sugars (monosaccharides)

e.g. glucose,fructose, galactose

HexosePentose

e.g. ribose,deoxyribosee.g. glyceraldehyde

Triose

CCC O

Double sugars (disaccharides)

Examplessucrose,lactose,maltose,cellobiose

Polysaccharides

Cellulose: Cellulose is a structural material in plantsand is made up of unbranched chains of β-glucosemolecules held together by 1, 4 glycosidic links. Asmany as 10 000 glucose molecules may be linkedtogether to form a straight chain. Parallel chainsbecome cross-linked with hydrogen bonds and formbundles of 60-70 molecules called microfibrils.Cellulose microfibrils are very strong and are a majorcomponent of the structural components of plants,such as the cell wall (photo, right).

Starch: Starch is also a polymer of glucose, but it ismade up of long chains of α-glucose molecules linkedtogether. It contains a mixture of 25-30% amylose(unbranched chains linked by α-1, 4 glycosidic bonds)and 70-75% amylopectin (branched chains with α-1,6 glycosidic bonds every 24-30 glucose units). Starchis an energy storage molecule in plants and is foundconcentrated in insoluble starch granules within plantcells (see photo, right). Starch can be easily hydrolysedby enzymes to soluble sugars when required.

Glycogen: Glycogen, like starch, is a branchedpolysaccharide. It is chemically similar to amylopectin,being composed of α-glucose molecules, but thereare more α-1,6 glycosidic links mixed with α-1,4 links.This makes it more highly branched and water-solublethan starch. Glycogen is a storage compound in animaltissues and is found mainly in liver and muscle cells(photo, right). It is readily hydrolysed by enzymes toform glucose.

Chitin: Chitin is a tough modified polysaccharidemade up of chains of β-glucose molecules. It ischemically similar to cellulose but each glucose hasan amine group (–NH2) attached. After cellulose,chitin is the second most abundant carbohydrate. Itis found in the cell walls of fungi and is the maincomponent of the exoskeleton of insects (right) andother arthropods.

1

4

Symbolic formof amylopectin

1, 6 glycosidicbonds createbranched chains

14

6

6

Many 1, 6glycosidic bondscreate a highlybranched molecule

Carbohydrates are a family of organic molecules made up of carbon, hydrogen, and oxygen atoms with the general formula (CH2O)x. The most common arrangements found in sugars are hexose (6 sided) or pentose (5 sided) rings. Simple sugars, or monosaccharides, may join together to form compound sugars (disaccharides and polysaccharides), releasing water in the process (condensation). Compound sugars can be broken down

into their constituent monosaccharides by the opposite reaction (hydrolysis). Sugars play a central role in cells, providing energy and, in some cells, contributing to support. They are the major component of most plants (60-90% of the dry weight) and are used by humans as a cheap food source, and a source of fuel, housing, and clothing. In all carbohydrates, the structure is closely related to their functional properties (below).

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1. Distinguish between structural and optical isomers in carbohydrates, describing examples of each:

2. Explain how the isomeric structure of a carbohydrate may affect its chemical behaviour:

3. Explain briefly how compound sugars are formed and broken down:

4. Discuss the structural differences between the polysaccharides cellulose, starch, and glycogen, explaining how the differences in structure contribute to the functional properties of the molecule:

2 mono-saccharides

CH2OH

C

H

OH

C

C

C

C

OH

H OH

HOH

H

OH

α glucose α glucose

IsomerismCompounds with the same chemical formula (sametypes and numbers of atoms) may differ in thearrangement of their atoms. Such variations in thearrangement of atoms in molecules are called isomers.In structural isomers (such as fructose and glucose,and the α and β glucose, right), the atoms are linked indifferent sequences. Optical isomers are identical inevery way but are mirror images of each other.

CH2OH

C

H

OH

C

C

C

C

OHO

H OH

HH

H

HO

β glucose

CH2OH

C

H

OH

C

C

C

C

OH

H OH

HOH

H

OH

α glucose

Condensation and Hydrolysis ReactionsMonosaccharides can combine to form compound sugars inwhat is called a condensation reaction. Compound sugars canbe broken down by hydrolysis to simple monosaccharides.

O

H2O

+Glycosidic bond

CH2OH

C

H

OH

C

C

C

C

OH

H OH

HOH

H

OH

CH2OH

C

H

OH

C

C

C

C

OH

H OH

HO

H

OH

MaltoseCH2OH

C

H

OH

C

C

C

C

OH

H OH

HOH

H

Hydrolysis reactionWhen a disaccharide is split,as in the process of digestion,a water molecule is used asa source of hydrogen and ahydroxyl group. The reactionis catalysed by enzymes.

Condensation reactionTwo monosaccharides arejoined together to form adisaccharide with the releaseof a water molecule (henceits name). Energy is suppliedby a nucleotide sugar (e.g.ADP-glucose).

Disaccharide + water

Glycosidic bond

Disaccharide + water

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The Chem

istry of Life

Related activities: Organic MoleculesWeb links: Biomolecules: Lipids, Formation of Triglycerides A 1

LipidsLipids are a group of organic compounds with an oily, greasy, or waxy consistency. They are relatively insoluble in water and tend to be water-repelling (e.g. cuticle on leaf surfaces). Lipids are important biological fuels, some are hormones, and some

serve as structural components in plasma membranes. Proteins and carbohydrates may be converted into fats by enzymes and stored within cells of adipose tissue. This store is increased during times of plenty, to be used during times of food shortage.

Although steroids are classified as lipids, their structure isquite different from that of other lipids. Steroids have a basicstructure of three rings made of 6 carbon atoms each and afourth ring containing 5 carbon atoms. Examples of steroidsinclude the male and female sex hormones (testosterone andoestrogen), and the hormones cortisol and aldosterone.Cholesterol, while not a steroid itself, is a sterol lipid and isa precursor to several steroid hormones.

Steroid

Triglyceride: an example of a neutral fat

Gly

cero

l

Fatty acid

Fatty acid

Fatty acid

The most abundant lipids in living things are neutral fats.They make up the fats and oils found in plants and animals.Fats are an economical way to store fuel reserves, since theyyield more than twice as much energy as the same quantityof carbohydrate. Neutral fats are composed of a glycerolmolecule attached to one (monoglyceride), two (diglyceride)or three (triglyceride) fatty acids. The fatty acid chains may besaturated or unsaturated (see below). Waxes are similar instructure to fats and oils, but they are formed with a complexalcohol instead of glycerol.

C

O

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

C

H

C

H

H

C

H

C

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

O

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

Formula (above) and molecular model (below)for palmitic acid (a saturated fatty acid)

Fatty acids are a major component of neutral fats andphospholipids. About 30 different kinds are found in animallipids. Saturated fatty acids contain the maximum numberof hydrogen atoms. Unsaturated fatty acids contain somecarbon atoms that are double-bonded with each other andare not fully saturated with hydrogens. Lipids containing ahigh proportion of saturated fatty acids tend to be solids atroom temperature (e.g. butter). Lipids with a high proportionof unsaturated fatty acids are oils and tend to be liquid atroom temperature. This is because the unsaturation causeskinks in the straight chains so that the fatty acids do not packclosely together. Regardless of their degree of saturation,fatty acids yield a large amount of energy when oxidised.

Saturated andUnsaturated Fatty Acids

Neutral Fats and Oils

Phospholipids

Phospholipids are the main component of cellular membranes.They consist of a glycerol attached to two fatty acid chainsand a phosphate (PO4

3-) group. The phosphate end of themolecule is attracted to water (it is hydrophilic) while the fattyacid end is repelled (hydrophobic). The hydrophobic ends turninwards in the membrane to form a phospholipid bilayer.

Phospholipid

Fatty acid

Fatty acid

Gly

cero

l

PO43-

Hydrophilic end

Hydrophobic end

Steroids

Triglycerides form whenglycerol bonds with threefatty acids. Glycerol is analcohol containing threecarbons. Each of thesecarbons is bonded to ahydroxyl (-OH) group.

When glycerol bonds withthe fatty acid, an esterbond is formed and wateris re leased. Threeseparate condensationreactions are involved inproducing a triglyceride.

C

H

C

CH

H

H

H

O

O

O CO CH2 CH3

CO CH2 CH3

CO CH2 CH3

C

H

C

CH

H

H

H

H

H

H

O

O

O CO CH2 CH3OH

CO CH2 CH3OH

CO CH2 CH3OH

OH H

OH H

OH H

Fatty acidsGlycerol

Triglyceride Water

Condensation

Formula (above) and molecular model (below)for linoleic acid (an unsaturated fatty acid)

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Important Biological Functions of Lipids

Lipids are concentrated sources of energyand provide fuel for aerobic respiration.

Phospholipids form the structural frameworkof cellular membranes.

Waxes and oils secreted on to surfacesprovide waterproofing in plants and animals.

Stored lipids provide insulation. Increasedbody fat reduces the amount of heat lost tothe environment (e.g. in winter or in water).

Lipids are a source of metabolic water. Duringrespiration, stored lipids are metabolised forenergy, producing water and carbon dioxide.

Fat absorbs shocks. Organs that are proneto bumps and shocks (e.g. kidneys) arecushioned with a relatively thick layer of fat.

TG

Plasma membrane

WM

U

1. Outline the key chemical difference between a phospholipid and a triglyceride:

2. Name the type of fatty acids found in lipids that form the following at room temperature:

(a) Solid fats: (b) Oils:

3. Relate the structure of phospholipids to their chemical properties and their functional role in cellular membranes:

4. (a) Distinguish between saturated and unsaturated fatty acids:

(b) Explain how the type of fatty acid present in a neutral fat or phospholipid is related to that molecule's properties:

(c) Suggest how the cell membrane structure of an Arctic fish might differ from that of tropical fish species:

5. Identify two examples of steroids. For each example, describe its physiological function:

(a) (b)

6. Explain how fats can provide an animal with: (a) Energy:

(b) Water:

(c) Insulation:

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The Chem

istry of Life

Related activities: Organic Molecules, Proteins, TranslationWeb links: Amino Acids and Peptide Bond Formation, Amino Acids and Proteins A 2

Amino Acids

General structure ofan amino acid

COOH

H

C

R

The 'R' group varies inchemical make-up witheach type of amino acid.

Carboxyl groupmakes the moleculebehave like a weak acid.

Hydrogenatom

Carbonatom

Aminegroup NH2

Example of an amino acidshown as a space filling

model: cysteine.

NH2 CO

OHC

R

H

Amino acids occurring in proteins

Alanine

Arginine

Asparagine

Aspartic acid

Cysteine

Serine

Threonine

Tryptophan

Tyrosine

Valine

Glycine

Histidine

Isoleucine

Glutamine

Glutamic acid

Proline

Leucine

Lysine

Methionine

Phenylalanine

Structure of Amino AcidsThere are over 150 amino acids foundin cells, but only 20 occur commonly inproteins. The remaining, non-proteinamino acids have specialised roles asintermediates in metabolic reactions, oras neurotransmitters and hormones. Allamino acids have a common structure(see right). The only difference betweenthe different types lies with the 'R' groupin the general formula. This group isvariable, which means that it is differentin each kind of amino acid.

The order of amino acids in a protein isdirected by the order of nucleotides in DNAand mRNA.

Peptide bonds link amino acids together inlong polymers called polypeptide chains.These may form part or all of a protein.

A polypeptide chain

This 'R' group givesthe amino acid anacidic property.

Cysteine

NH2 COOHC

CH2

SH

H

Lysine

NH2 COOHC

CH2

CH2

CH2

CH2

H

NH2

Aspartic acid

NH2 COOHC

H

CH 2

COOH

This 'R' group givesthe amino acid analkaline property.

This 'R' group can formdisulfide bridges withother cysteines to createcross linkages in apolypeptide chain.

Properties of Amino AcidsThree examples of amino acids withdifferent chemical properties are shownright, with their specific 'R' groupsoutlined. The 'R' groups can have quitediverse chemical properties.

The amino acids are linked together by peptide bonds toform long chains of up to several hundred amino acids(called polypeptide chains). These chains may be functionalunits (complete by themselves) or they may need to bejoined to other polypeptide chains before they can carryout their function. In humans, not all amino acids can bemanufactured by our body: ten must be taken in with ourdiet (eight in adults). These are the 'essential amino acids'(indicated by the symbol on the right).

Several amino acids act as neurotransmitters inthe central nervous sytem. Glutamic acid andGABA (gamma amino butyric acid) are the mostcommon neurotransmitters in the brain. Others,such as glycine, are restricted to the spinal cord.

Amino acids tend to stabilise the pH of solutionsin which they are present (e.g. blood and tissuefluid) because they will remove excess H+ orOH– ions. They retain this buffer capacity evenwhen incorporated into peptides and proteins.

Amino acids are widely available as dietarysupplements for specific purposes. Lysine is soldas a relief for herpes infections and glucosaminesupplements are used for alleviating thesymptoms of arthritis and other joint disorders.

Peptidebond

Peptidebond

Peptidebond

Peptidebond

Peptidebond

Peptidebond

Peptidebond

Neurones SEM: blood cells

EII

EII

Amino acids are the basic units from which proteins are made. Plants can manufacture all the amino acids they require from simpler molecules, but animals must obtain a certain number of ready-made amino acids (called essential amino acids) from their diet. Which amino acids are essential varies from species to species, as different metabolisms are able to synthesise different

substances. The distinction between essential and non-essential amino acids is somewhat unclear though, as some amino acids can be produced from others and some are interconvertible by the urea cycle. Amino acids can combine to form peptide chains in a condensation reaction. The reverse reaction, which breaks up peptide chains uses water and is called hydrolysis.

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24

1. Discuss the various biological roles of amino acids:

2. Describe what makes each of the 20 amino acids found in proteins unique:

3. Describe the process that determines the sequence in which amino acids are linked together to form polypeptide chains:

4. Explain how the chemistry of amino acids enables them to act as buffers in biological tissues:

5. Giving examples, explain what is meant by an essential amino acid:

6. Describe the processes by which amino acids are joined together and broken down:

Condensation and Hydrolysis Reactions

Amino acid Amino acid

N CC

R

HH

H O

OHN CC

R

HH

H O

OH

N CC

R

HH

HO

N CC

R

H

HO

OH

Hydrolysisreaction

Condensationreaction

Two aminoacids

Peptide bond

Hydrolysis reactionWhen a dipeptide is split,as occurs in the process ofdigestion, a water moleculeprovides a hydrogen and ahydroxyl group.

Condensation reactionTwo amino acids are joinedto form a dipeptide with therelease of a water molecule(hence its name).

H2ODipeptide +H2ODipeptide +

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25

The Chem

istry of Life

Related activities: Organic Molecules, Amino Acids, Modification of ProteinsWeb links: Amino Acids and Proteins RA 2

Proteins

GluSer

Ala

Ala

Met

IsoSerTyr

Glu

Phe

Amino acid

Amino acid sequence

Beta chain:146 amino

acids

Alpha chain:141 amino

acids

In haemoglobin, eachpolypeptide enclosesan iron-containingprosthetic group.

Haemoglobinmolecule

Peptidebond

β-pleated sheet

Hydrogenbonds

Twopeptidechains

Alpha (α) helix

The helical shapeis maintained withhydrogen bonds

or

C3032H4816O872N780S8Fe4

Haemoglobin'schemical formula:

Primary Structure - 1° (amino acid sequence)Strings of hundreds of amino acids link together with peptidebonds to form molecules called polypeptide chains. There are 20different kinds of amino acids that can be linked together in a vastnumber of different combinations. This sequence is called theprimary structure. It is the arrangement of attraction andrepulsion points in the amino acid chain that determines the higherlevels of organisation in the protein and its biological function.

Secondary Structure - 2° (α-helix or ß pleated sheet)Polypeptides become folded in various ways, referred to as thesecondary (2°) structure. The most common types of 2° structuresare a coiled α-helix and a β-pleated sheet. Secondary structuresare maintained with hydrogen bonds between neighbouring COand NH groups. H-bonds, although individually weak, provideconsiderable strength when there are a large number of them.The example, right, shows the two main types of secondarystructure. In both, the 'R' side groups (not shown) project outfrom the structure. Most globular proteins contain regions of α-helices together with β-sheets. Keratin (a fibrous protein) iscomposed almost entirely of α-helices. Fibroin (silk protein), isanother fibrous protein, almost entirely in β-sheet form.

Tertiary Structure - 3° (folding)Every protein has a precise structure formed by the folding of thesecondary structure into a complex shape called the tertiarystructure. The protein folds up because various points on thesecondary structure are attracted to one another. The strongestlinks are caused by bonding between neighbouring cysteineamino acids which form disulfide bridges. Other interactions thatare involved in folding include weak ionic and hydrogen bonds aswell as hydrophobic interactions.

Quaternary Structure - 4°Some proteins (such as enzymes) are complete and functionalwith a tertiary structure only. However, many complex proteinsexist as aggregations of polypeptide chains. The arrangement ofthe polypeptide chains into a functional protein is termed thequaternary structure. The example (right) shows a molecule ofhaemoglobin, a globular protein composed of 4 polypeptide sub-units joined together; two identical beta chains and two identicalalpha chains. Each has a haem (iron containing) group at thecentre of the chain, which binds oxygen. Proteins containing non-protein material are conjugated proteins. The non-protein partis the prosthetic group.

Denaturation of ProteinsDenaturation refers to the loss of the three-dimensional structure(and usually also the biological function) of a protein. Denaturationis often, although not always, permanent. It results from analteration of the bonds that maintain the secondary and tertiarystructure of the protein, even though the sequence of amino acidsremains unchanged. Agents that cause denaturation are:• Strong acids and alkalis: Disrupt ionic bonds and result in

coagulation of the protein. Long exposure also breaks downthe primary structure of the protein.

• Heavy metals: May disrupt ionic bonds, form strong bonds withthe carboxyl groups of the R groups, and reduce protein charge.The general effect is to cause the precipitation of the protein.

• Heat and radiation (e.g. UV): Cause disruption of the bondsin the protein through increased energy provided to the atoms.

• Detergents and solvents: Form bonds with the non-polargroups in the protein, thereby disrupting hydrogen bonding.

Polypeptide chain

Disulfidebridge

1°

2°

3°

4°

The precise folding of a protein into its tertiary structure creates a three dimensional arrangement of the active 'R' groups. It is this structure that gives a protein its unique chemical properties. If a protein loses this precise structure (through denaturation), it is usually unable to carry out its biological function. Proteins can be classified on the basis of structure (e.g. globular vs fibrous) or function, as described on the next page. The entire collection of

proteins in a particular cell type is termed the cellular proteome, while the complete proteome for an organism comprises all the various cellular proteomes. An organism's proteome is larger than its genome in the sense that there are more proteins than genes. This is the result of alternative splicing of genes and modifications made to proteins after they are translated, such as phosphorylation and glycosylation (see the next activities).

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1. Giving examples, briefly explain how proteins are involved in the following functional roles:

(a) Structural tissues of the body:

(b) Regulating body processes:

(c) Contractile elements:

(d) Immunological response to pathogens:

(e) Transporting molecules within cells and in the bloodstream:

(f) Catalysing metabolic reactions in cells:

2. Explain how denaturation destroys protein function:

3. Suggest why fibrous proteins are important as structural molecules in cells:

4. Suggest why many globular proteins, in contrast to fibrous proteins, have a catalytic or regulatory role:

Fibrous Proteins Globular Proteins

Properties • Water insoluble

• Very tough physically; may be supple or stretchy

• Parallel polypeptide chains in long fibres or sheets

Function • Structural role in cells and organisms e.g. collagenfound in connective tissue, cartilage, bones,tendons, and blood vessel walls.

• Contractile e.g. myosin, actin

Structural Classification of Proteins

Collagen consists of three helicalpolypeptides wound around eachother to form a ‘rope’. Every thirdamino acid in each polypeptide is aglycine (Gly) molecule wherehydrogen bonding occurs, holding thethree strands together.

Glycine

Hydrogen bond

Fibres form due tocross links betweencollagen molecules.

Bovine insulin is a relatively small protein consisting oftwo polypeptide chains (an α chain and a β chain). Thesetwo chains are held together by disulfide bridges betweenneighbouring cysteine (Cys) molecules.

Gin Asn Cys AsnLeu Tyr Gin Leu Tyr

Ser

Gly IIe Val Glu Gin Cys

Cys

Ala

Ser

Val

Cys

Thr

Tyr

Phe

Phe

Gly

Arg

Gin

Pro

Lys

Ala

Leu

Tyr

Leu

AlaGinValLeuHis

CysVal

Phe SerGlyCysLeuHisGinAsnVal

α chain

β chain

disulfide bond

Properties • Easily water soluble

• Tertiary structure critical to function

• Polypeptide chains folded into a spherical shape

Function • Catalytic e.g. enzymes• Regulatory e.g. hormones (insulin)• Transport e.g. haemoglobin• Protective e.g. antibodies

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27

The Chem

istry of Life

Related activities: Review of Cell Ultrastructure, Packaging Macromolecules A 2

Membranes in CellsMany of the important structures and organelles in cells are composed of, or are enclosed by, membranes. These include: the endoplasmic reticulum, mitochondria, nucleus, Golgi body, chloroplasts, lysosomes, vesicles and the cell plasma membrane itself. All membranes within eukaryotic cells share the same basic structure as the plasma membrane that

encloses the entire cell. They perform a number of critical functions in the cell: serving to compartmentalise regions of different function within the cell, controlling the entry and exit of substances, and fulfilling a role in recognition and communication between cells. Some of these roles are described below.

Containment of DNAThe nucleus is surrounded by anuclear envelope of two membranes,forming a separate compartment forthe cell’s genetic material.

Compartmentation within MembranesMembranes play an important role in separatingregions within the cell (and within organelles) whereparticular reactions occur. Specific enzymes aretherefore often located in particular organelles. Thereaction rate is controlled by controlling the rate atwhich substrates enter the organelle and therefore theavailability of the raw materials required for thereactions.

Example: The enzymes involved in cellular respirationare arranged in different parts of the mitochondria.The various reactions are localised and separated bymembrane systems.

Amine oxidases andother enzymes on theouter membrane surface

Adenylate kinase andother phosphorylasesbetween the membranes

Respiratory assemblyenzymes embedded inthe membrane (ATPase)

Many soluble enzymesof the Krebs cyclefloating in the matrix, aswell as enzymes for fattyacid degradation.Cross-section of a mitochondrion

Matrix

Packaging and secretionThe Golgi apparatus is aspecialised membrane-boundorganelle which produceslysosomes and compartmentalisesthe modification, packaging andsecretion of substances such asproteins and hormones.

Energy transfer The reactions of cellular respiration (andphotosynthesis in plants) take place in the membrane-boundenergy transfer systems occurring in mitochondria andchloroplasts respectively. See the example explained below.

Cell communication and recognitionThe proteins embedded in themembrane act as receptor moleculesfor hormones and neurotransmitters.Glycoproteins and glycolipids stabilisethe plasma membrane and act as cellidentity markers, helping cells toorganise themselves into tissues, andenabling foreign cells to be recognised.

Transport processesChannel and carrier proteins areinvolved in selective transport across theplasma membrane. Cholesterol in themembrane can help to prevent ions orpolar molecules from passing throughthe membrane (acting as a plug).Entry and export of substances The plasma

membrane may take up fluid or solid materialand form membrane-bound vesicles (or largervacuoles) within the cell. Membrane-boundtransport vesicles move substances to the innersurface of the cell where they can be exportedfrom the cell by exocytosis.

Isolation of enzymes Membrane-bound lysosomes contain enzymes forthe destruction of wastes and foreignmaterial. Peroxisomes are the site fordestruction of the toxic and reactivemolecule, hydrogen peroxide (formedas a result of some cellular reactions).

Role in protein and membrane synthesisSome protein synthesis occurs on freeribosomes, but much occurs on membrane-bound ribosomes on the rough endoplasmicreticulum. Here, the protein is synthesiseddirectly into the space within the ERmembranes. The rough ER is also involvedin membrane synthesis, growing in placeby adding proteins and phospholipids.

Role in lipid synthesisThe smooth ER is the site oflipid and steroid synthesis.

1. Discuss the importance of membrane systems and organelles in providing compartments within the cell:

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2. Match each of the following organelles with the correct description of its functional role in the cell:

chloroplast, rough endoplasmic reticulum, lysosome, smooth endoplasmic reticulum, mitochondrion, Golgi apparatus

(a) Active in synthesis, sorting, and secretion of cell products:

(b) Digestive organelle where macromolecules are hydrolysed:

(c) Organelle where most cellular respiration occurs and most ATP is generated:

(d) Active in membrane synthesis and synthesis of secretory proteins:

(e) Active in lipid and hormone synthesis and secretion:

(f) Photosynthetic organelle converts light energy to chemical energy stored in sugar molecules:

3. Explain how the membrane surface area is increased within cells and organelles:

4. Discuss the importance of each of the following to cellular function:

(a) High membrane surface area:

(b) Channel proteins and carrier proteins in the plasma membrane:

5. Non-polar (lipid-soluble) molecules diffuse more rapidly through membranes than polar (lipid-insoluble) molecules:

(a) Explain the reason for this:

(b) Discuss the implications of this to the transport of substances into the cell through the plasma membrane:

Pho

tos:

WM

U u

nles

s ot

herw

ise

stat

ed.

BF

The nuclear membrane, which surroundsthe nucleus, regulates the passage of geneticinformation to the cytoplasm and may alsoprotect the DNA from damage.

The Golgi apparatus comprises stacks ofmembrane-bound sacs (S). It is involved inpackaging materials for transport or exportfrom the cell as secretory vesicles (V).

V

S

Mitochondria have an outer membrane (O)which controls the entry and exit of materialsinvolved in aerobic respiration. Inner membranes(I) provide attachment sites for enzyme activity.

I

O

The plasma membrane surrounds the cell.In this photo, intercellular junctions calleddesmosomes, which connect neighbouringcells, are indicated with arrows.

Chloroplasts are large organelles found inplant cells. The stacked membrane systemsof chloroplasts (grana) trap light energy whichis then used to fix carbon into 6-C sugars.

Grana

This EM shows stacks of rough endoplasmicreticulum (arrows). The membranes arestudded with ribosomes, which synthesizeproteins into the intermembrane space.

Functional Roles of Membranes in Cells

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29

The Chem

istry of Life

Web links: Eukaryotic Cells Interactive Animation RA 1

Review of Cell Ultrastructure The table below provides a format to summarise information about structures and organelles of typical eukaryotic cells. Complete the table using the list provided and by referring to a textbook and to other pages in this topic. Fill in the final three columns by writing either ‘YES’ or ‘NO’. The first cell component has been completed for you as a guide and the log scale of

measurements (top of next page) illustrates the relative sizes of some cellular structures. List of structures and organelles: cell wall, mitochondrion, chloroplast, cell junctions, centrioles, ribosome, flagella, endoplasmic reticulum, Golgi apparatus, nucleus, flagella, cytoskeleton and vacuoles.

DetailsPresent in

Plantcells

Animalcells

Visibleunder lightmicroscope

Cell Component

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

Double layer of phospholipids(called the lipid bilayer)

Proteins

YES YES YES(but not at thelevel of detailshown in the

diagram)

Plasma (cell surface) membrane

Surrounding the cell

Gives the cell shape and protection. Italso regulates the movement ofsubstances into and out of the cell.

(a)

Innermembrane

Outermembrane

Matrix

Cristae

(c)

Cisternae

Secretory vesiclesbudding off

Transfer vesiclesfrom the smooth

endoplasmic reticulum

(d)

RoughTransportpathway

Ribosomes

Flattened membrane sacs

SmoothVesiclesbudding off

(e)

Stroma

Grana comprise stacksof thylakoids

Lamellae

(f)

(b)

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0.1 nm 1 nm 10 nm 100 nm 1 mm 10 mm

DNA

Ribosome Golgi Nucleus Animal cell Plant cell

Leaf section LeafPlasma membrane

DetailsPresent in

Plantcells

Animalcells

Visibleunder lightmicroscope

Cell Component

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

Microtubules

(g)

(h)

Two central,singlemicrotubules

Extension of plasmamembrane surroundinga core of microtubulesin a 9+2 pattern

9 doublets ofmicrotubules in anouter ring

Basal bodyanchors the cilium

Cilia and flagella (some eukaryotic cells)

(i)

(j)

Lysosome and food vacuole

Phagocytosisof food particle

FoodVacuole

LysosomeDigestion

Nuclearpores

Genetic material

Nucleolus

Nuclear membrane

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31The C

hemistry of Life

DetailsPresent in

Plantcells

Animalcells

Visibleunder lightmicroscope

Cell Component

Name:

Location:

Function:

Name:

Location:

Function:

Name:

Location:

Function:

(l)

(k)

Desmosome

Gapjunction

Tightjunction

Extracellular matrix

(m) Cell junctions

Pectins

Hemicelluloses

Cellulose fibres

Middle lamella

Plasma membrane

Microfilament

Intermediatefilament

Organelle

Microtubule

Cellulose cell wall

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32

EA 1 Related activities: Enzyme Reaction Rates

1. Explain why it is possible to separate cell organelles using centrifugation:

2. Suggest why the sample is homogenised before centrifugation:

3. Explain why the sample must be kept in a solution that is:

(a) Isotonic:

(b) Cool:

(c) Buffered:

4. Density gradient centrifugation is another method of cell fractionation. Sucrose is added to the sample, which is then centrifuged at high speed. The organelles will form layers according to their specific densities. Using the information above, label the centrifuge tube on the right with the organelles you would find in each layer.

Cell FractionationDifferential centrifugation (also called cell fractionation) is a technique used to extract organelles from cells so that they can be studied. The aim is to extract undamaged intact organelles. Samples must be kept very cool so that metabolism is slowed

and self digestion of the organelles is prevented. The samples must also be kept in a buffered, isotonic solution so that the organelles do not change volume and the enzymes are not denatured by changes in pH.

Differential Centrifugation

The sample is chilled overice and cut into smallpieces in a cold, buffered,isotonic solution.

200 mL

500 mL

L

1 The filtrate is centrifugedat low speed to removepartially opened cells andsmall pieces of debris.

RPM0

1000

2000

On/OffSpeed Timer

4The sample is homogenisedthoroughly beforecentrifugation. The cellorganelles remain intact.

BBT Inc.Power Speed

2

Debris

Supernatant usedfor the next roundof centrifuging.

The supernatantcontaining the organellesis carefully decanted off.

5

Ribosomes andendoplasmicreticulum

The sample is centrifugedat 100 000 g for 60 minutesthen decanted.

8

Nuclei

Supernatant usedfor the next roundof centrifuging.

The sample is centrifugedat 500-600 g for 5-10minutes then decanted.

6

Supernatant usedfor the next roundof centrifuging.

Lysosomes andmitochondria

The sample is centrifugedat 10 000-20 000 g for 15-20 minutes then decanted.

7

NOTE: In centrifugation, the relative centrifugal force (RCF) is expressed as ‘g’, where g represents the gravitational field strength.

The homogenisedsuspension is filtered toremove cellular debris. Itis kept cool throughout.

500 mL

3

Density gradient centrifugation

(c)

(b)

(d) Cellular debris

(a)

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33

The Chem

istry of Life

Related activities: Proteins, Cell Signalling A 2

Modification of ProteinsProteins may be modified after they have been produced by the ribosomes. After they pass into the interior of the rough endoplasmic reticulum, some proteins may have carbohydrates added to form glycoproteins. Proteins may be further altered in the Golgi apparatus. The Golgi apparatus functions principally as a system for processing, sorting, and modifying proteins. Proteins that are to be secreted from the cell are synthesised by

ribosomes on the rough endoplasmic reticulum and transported to the Golgi apparatus. At this stage, carbohydrates may be removed or added in a step-wise process. Some of the possible functions of glycoproteins are illustrated below. Other proteins may have fatty acids added to them to form lipoproteins. These modified proteins transport lipids in the plasma between various organs in the body (e.g. gut, liver, and adipose tissue).

Enlarged section of a plasma membraneshowing a glycoprotein embedded in it.

Plasmamembrane

Carbohydratesare attached tothe protein

Protein

Branching chains ofcarbohydrates are madeup of different kinds ofsugars linked together.

Inside of the cell(cytosol)

Sugars:e.g. glucose,mannose and

galactose

Glycoprotein

Carbohydrate groups may helpposition or orientate glycoproteinsin membranes. The carbohydrategroups prevent them from rotatingin the membrane.

Carbohydrate groups may act as markers thatdetermine the destination of a glycoprotein withinthe cell or for export. The carbohydrates may beremoved after the protein has reached its destination.

Glycoprotein

Carbohydrates on cell surfaces maybe important in intercellularrecognition; the interaction of differentcells to form tissue and the detectionof foreign cells by the immune system.

XGlycoprotein

Plasma membrane

Nearly all proteins synthesised byribosomes bound to the endoplasmicreticulum acquire carbohydrate unitsthat are attached to them.

Proteins made by freeribosomes in the cytosol arealmost devoid of carbohydrate.

Golgiapparatus

Nucleus

Cutaway section of a cell

Cytosol

Endoplasmic reticulum

1. (a) Explain what a glycoprotein is:

(b) Briefly describe three roles of glycoproteins:

2. (a) Explain what a lipoprotein is:

(b) Briefly describe the role of lipoproteins:

3. Suggest why proteins made by free ribosomes in the cytosol are usually free of carbohydrate:

4. Suggest why the orientation of a protein in the plasma membrane might be important:

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Related activities: Organic Molecules, Membranes in Cells, Modification of ProteinsRA 2

Transportvesicles

Ribosomes

Endoplasmicreticulum (ER)

Golgi apparatus

Smooth EREnzymes of the smooth ER areimportant to the synthesis of fats,phospholipids, steroid hormones,and other lipids.

Rough ERProteins destined for secretionare assembled by ribosomesattached to the rough ER.

Golgi apparatusThe Golgi apparatus comprises stacks of flattened membranes in theshape of curved sacs. This organelle receives transport vesicles andthe products they contain from smooth ER. They are modified, storedand eventually shipped to the surface of the cell or other destinations.

Ribosomes

Cisternal space(inside of ER)

Membraneof rough ER

Typical cell

Golgi apparatus producesvesicles that are transported

to the outside of the cell.

Golgi apparatusreceives transport

vesicles from the ER

Polypeptide chainbeing formed by

the process ofprotein synthesis

1. A polypeptide chain grows from a bound ribosome.

2. The chain is threaded through the ER membrane into thecisternal space, possibly through a pore.

3. As it enters the cisternal space inside the ER, it folds up intoits correct 3-dimensional shape.

4. Most proteins destined for secretion are glycoproteins (i.e.they are proteins with carbohydrates added to them); thecarbohydrate is attached to the protein by enzymes.

5. The ER membrane keeps proteins for secretion separatefrom proteins made by free ribosomes in the cytosol.

6. Proteins destined for secretion leave the ER wrapped intransport vesicles which bud off from the end of the ER.

7. These vesicles are received by the Golgi apparatus,modified, stored and eventually shipped to the cell's surface,where they can be exported from the cell by exocytosis.

Creating Proteins for Exocytotic Secretion

Cells produce a range of organic polymers made up of repeating units of smaller molecules. The synthesis, packaging and movement of these macromolecules inside the cell involves

a number of membrane bound organelles, as indicated below. These organelles provide compartments where the enzyme systems involved can be isolated.

Packaging Macromolecules

1. Using examples, explain what is meant by a macromolecule:

2. Suggest why polypeptides requiring transport are synthesised by membrane-bound (rather than free) ribosomes:

3. Suggest why most proteins destined for secretion from the cell are glycoproteins:

4. Briefly describe the roles of the following organelles in the production of macromolecules: (a) Rough ER:

(b) Smooth ER:

(c) Golgi apparatus:

(d) Transport vesicles:

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35

The Chem

istry of Life

Related activities: Organic Molecules, DNA Molecules, Creating a DNA Molecule A 1

Nucleic Acids

The two-ringed bases above are purines and makeup the longer bases. The single-ringed bases arepyrimidines. Although only one of four kinds of basecan be used in a nucleotide, uracil is found only inRNA, replacing thymine. DNA contains: A, T, G, andC, while RNA contains A, U, G, and C.

Deoxyribose sugar is found only in DNA. It differsfrom ribose sugar, found in RNA, by the lack of asingle oxygen atom (arrowed).

Bases

Sugars

Purines:

Pyrimidines:

RNA Molecule

Ribonucleic acid (RNA)comprises a single strand ofnucleotides linked together.

A

C

U

G

In RNA, uracilreplaces thyminein the code.

Ribosesugar

Symbolic Form of a Nucleotide

Chemical Structure of a Nucleotide

APhosphate: Linksneighbouringsugars together.

Sugar: One of two typespossible: ribose in RNAand deoxyribose in DNA.

Base: One of four typespossible (see box on right). Thispart of the nucleotide comprisesthe coded genetic message.

Nucleotides are the building blocks of DNA. Their precise sequence in aDNA molecule provides the genetic instructions for the organism to whichit governs. Accidental changes in nucleotide sequences are a cause ofmutations, usually harming the organism, but occasionally providing benefits.

OCH2

H

HOH

H HH

O

N

N

N

N

NH2

P O

O

OH

OH

Phosphate Sugar Base

Deoxyribonucleic acid (DNA) comprises a double strand of nucleotides linkedtogether. It is shown unwound in the symbolic representation (left). The DNA moleculetakes on a twisted, double helix shape as shown in the space filling model on the right.

DNA Molecule

T

A

C

G

A

C

T

GDeoxyribosesugar

DNA Molecule

Space filling modelSymbolic representation

Hydrogen bondshold the twostrands together.Only certainbases can pair.

OH HRibose Deoxyribose

Adenine Guanine

A G

Cytosine

C

Thymine(DNA only)

T

Uracil(RNA only)

U

Nucleic acids are a special group of chemicals in cells concerned with the transmission of inherited information. They have the capacity to store the information that controls cellular activity. The central nucleic acid is called deoxyribonucleic acid (DNA). DNA is a major component of chromosomes and is found primarily in the nucleus, although a small amount is found in mitochondria and chloroplasts. Other ribonucleic acids (RNA) are involved in the ‘reading’ of the DNA information. All nucleic acids are made

up of simple repeating units called nucleotides, linked together to form chains or strands, often of great length (see the activity DNA Molecules). The strands vary in the sequence of the bases found on each nucleotide. It is this sequence which provides the ‘genetic code’ for the cell. In addition to nucleic acids, certain nucleotides and their derivatives are also important as suppliers of energy (ATP) or as hydrogen ion and electron carriers in respiration and photosynthesis (NAD, NADP, and FAD).

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Double-Stranded DNA

The double-helix structure of DNA is like a ladder twistedinto a corkscrew shape around its longitudinal axis. It is‘unwound’ here to show the relationships between the bases.

• The way the correct pairs of bases are attracted to eachother to form hydrogen bonds is determined by the numberof bonds they can form and the shape (length) of the base.

• The template strand the side of the DNA molecule thatstores the information that is transcribed into mRNA. Thetemplate strand is also called the antisense strand.

• The other side (often called the coding strand) has thesame nucleotide sequence as the mRNA except that T inDNA substitutes for U in mRNA. The coding strand is alsocalled the sense strand.

C

T

Two nucleotides are linkedtogether by a condensationreaction between thephosphate of one nucleotideand the sugar of another.

Formation of a nucleotide Formation of adinucleotide

Condensation(water removed)

AH2O

H2O

A

A nucleotide is formed when phosphoric acid and a base are chemically bonded to a sugarmolecule. In both cases, water is given off, and they are therefore condensation reactions.In the reverse reaction, a nucleotide is broken apart by the addition of water (hydrolysis).

H2O

T

A

C

G

AC T

G

3'

5'

5'

3'

1. The diagram above depicts a double-stranded DNA molecule. Label the following parts on the diagram: (a) Sugar (deoxyribose) (d) Purine bases (b) Phosphate (e) Pyrimidine bases (c) Hydrogen bonds (between bases)

2. (a) Explain the base-pairing rule that applies in double-stranded DNA:

(b) Explain how this differs in mRNA:

(c) Describe the purpose of the hydrogen bonds in double-stranded DNA:

3. Describe the functional role of nucleotides:

4. Distinguish between the template strand and coding strand of DNA, identifying the functional role of each:

5. Complete the following table summarising the differences between DNA and RNA molecules:

DNA RNA

Sugar present

Bases present

Number of strands

Relative length

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37

The Chem

istry of Life

Related activities: Proteins, Enzyme Reaction Rates, Metabolic Pathways, Gene Mutations Web links: How Enzymes Work RA 2

EnzymesMost enzymes are proteins. They are capable of catalysing (speeding up) biochemical reactions and are therefore called biological catalysts. Enzymes act on one or more compounds (called the substrate). They may break a single substrate molecule down into simpler substances, or join two or more substrate molecules chemically together. The enzyme itself is unchanged in the reaction; its presence merely allows the reaction to take place more rapidly. When the substrate attains the required activation energy to enable it to change into the product, there is a 50% chance that it will proceed forward to form the product, otherwise it reverts back to a stable form of

the reactant again. The part of the enzyme's surface into which the substrate is bound and undergoes reaction is known as the active site. This is made of different parts of polypeptide chain folded in a specific shape so they are closer together. For some enzymes, the complexity of the binding sites can be very precise, allowing only a single kind of substrate to bind to it. Some other enzymes have lower specificity and will accept a wide range of substrates of the same general type (e.g. lipases break up any fatty acid chain length of lipid). This is because the enzyme is specific for the type of chemical bond involved and not an exact substrate.

Enzyme StructureThe model on the right is of an enzyme calledRibonuclease S, that breaks up RNAmolecules. It is a typical enzyme, being aglobular protein and composed of up to severalhundred atoms. The darkly shaded areas arecalled active sites and make up the cleft; theregion into which the substrate molecule(s) aredrawn. The correct positioning of these sites iscritical for the catalytic reaction to occur. Thesubstrate (RNA in this case) is drawn into thecleft by the active sites. By doing so, it puts thesubstrate molecule under stress, causing thereaction to proceed more readily.

The presence of an enzyme simply makes it easier for a reaction to take place.All catalysts speed up reactions by influencing the stability of bonds in thereactants. They may also provide an alternative reaction pathway, thus loweringthe activation energy needed for a reaction to take place (see the graph below).

Source: After Biochemistry, (1981) by Lubert Stryer

Active sites: These attraction pointsdraw the substrate to the enzyme’ssurface. Substrate molecule(s) arepositioned in a way to promote a reaction:either joining two molecules together orsplitting up a larger one (as in this case).

Enzyme molecule: The complexityof the active site is what makes eachenzyme so specific (i.e. precise interms of the substrate it acts on).

Substrate molecule: Substrate molecules arethe chemicals that an enzyme acts on. Theyare drawn into the cleft of the enzyme.

How Enzymes WorkThe lock and key model proposed earlier this century suggested that thesubstrate was simply drawn into a closely matching cleft on the enzyme molecule.More recent studies have revealed that the process more likely involves aninduced fit (see diagram on the right), where the enzyme or the reactants changetheir shape slightly. The reactants become bound to enzymes by weak chemicalbonds. This binding can weaken bonds within the reactants themselves, allowingthe reaction to proceed more readily.

1 2 3Enzyme

Substrate

Products

Induced Fit ModelAn enzyme fits to its substrate somewhatlike a lock and key. The shape of theenzyme changes when the substrate fitsinto the cleft (called the induced fit):

The enzyme changes shape, forcingthe substrate molecules to combine.

2

The resulting end product is releasedby the enzyme which returns to itsnormal shape, ready to receive more.

3

Two substrate molecules are drawninto the cleft of the enzyme.

1

Enzyme

EnzymeCleft

Substratemolecules

End productreleasedEnzyme

Enzyme

Enzymechangesshape

Am

ount

of e

nerg

y st

ored

in t

he c

hem

ical

s

Direction of reaction

Reactant

Product

Highenergy

Lowenergy

With enzyme: The activation energyis reduced by the presence of theenzyme and the reactants turn intoproducts more readily.

Without enzyme: The energyrequired for the reaction toproceed in the forward direction(the activation energy) is highwithout the enzyme present.

Start FinishLow

High

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1. Give a brief account of enzymes as biological catalysts, including reference to the role of the active site:

2. Distinguish between catabolism and anabolism, giving an example of each and identifying each reaction as endergonic or exergonic:

3. Outline the key features of the ‘lock and key’ model of enzyme action:

4. Outline the ‘induced fit’ model of enzyme action, explaining how it differs from the lock and key model:

5. Identify two factors that could cause enzyme denaturation, explaining how they exert their effects (see the next activity):

(a)

(b)

6. Explain what might happen to an enzyme's function if the gene that codes for it was altered by a mutation:

Anabolic reactionsSome enzymes can cause two substrate molecules to be drawninto the active site. Chemical bonds are formed, causing the twosubstrate molecules to form bonds and become a single molecule.Examples: protein synthesis, photosynthesis.

The two substrate moleculesare attracted to the enzymeby the 'active sites'.

The substratemolecules aresubjected to stresswhich will aid theformation of bonds.

The two substrate moleculesform a single product and arereleased to allow the enzymeto work again.

Substrates

Product

Enzyme

Catabolic reactionsSome enzymes can cause a single substrate molecule to bedrawn into the active site. Chemical bonds are broken, causingthe substrate molecule to break apart to become two separatemolecules. Examples: digestion, cellular respiration.

The substrate isattracted to the enzymeby the 'active sites'.

The substrate issubjected to stresswhich will facilitate thebreaking of bonds.

The substrate is cleaved(broken in two) and the twoproducts are released to allowthe enzyme to work again.

Substrate

ProductsEnzyme

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The Chem

istry of Life

Related activities: Enzyme Cofactors and Inhibitors RDA 2

1. Enzyme concentration (a) Describe the change in the rate of reaction when the enzyme concentration

is increased (assuming there is plenty of the substrate present):

(b) Suggest how a cell may vary the amount of enzyme present in a cell:

2. Substrate concentration (a) Describe the change in the rate of reaction when the substrate concentration

is increased (assuming a fixed amount of enzyme and ample cofactors):

(b) Explain why the rate changes the way it does:

3. Temperature Higher temperatures speed up all reactions, but few enzymes can tolerate

temperatures higher than 50–60°C. The rate at which enzymes are denatured (change their shape and become inactive) increases with higher temperatures.

(a) Describe what is meant by an optimum temperature for enzyme activity:

(b) Explain why most enzymes perform poorly at low temperatures:

4. Acidity (pH) Like all proteins, enzymes are denatured by extremes of pH (very acid or

alkaline). Within these extremes, most enzymes are still influenced by pH. Each enzyme has a preferred pH range for optimum activity.

(a) State the optimum pH for each of the enzymes:

Pepsin: Trypsin: Urease:

(b) Pepsin acts on proteins in the stomach. Explain how its optimum pH is suited to its working environment:

Enzyme Reaction Rates

Enzyme concentration

With ample substrateand cofactors present

Rat

e of

rea

ctio

n

Concentration of substrate

With fixed amount of enzymeand ample cofactors present

Rat

e of

rea

ctio

n

Optimum temperaturefor enzyme

Temperature (°C)

0 10 20 30 40 50

Enz

yme

activ

ity

Too cold forthe enzymeto operate

Rapiddenaturationat hightemperature

pH

Pepsin

Trypsin

Enz

yme

activ

ity

Acid Alkaline1 2 3 4 5 6 7 8 9 10

Urease

Enzymes are sensitive molecules. They often have a narrow range of conditions under which they operate properly. For most of the enzymes associated with plant and animal metabolism, there is little activity at low temperatures. As the temperature increases, so too does the enzyme activity, until the point is reached where the temperature is high enough to damage the enzyme’s structure. At this point, the enzyme ceases to function; a phenomenon called enzyme or protein denaturation.

Extremes in acidity (pH) can also cause the protein structure of enzymes to denature. Poisons often work by denaturing enzymes or occupying the enzyme’s active site so that it does not function. In some cases, enzymes will not function without cofactors, such as vitamins or trace elements. In the four graphs below, the rate of reaction or degree of enzyme activity is plotted against each of four factors that affect enzyme performance. Answer the questions relating to each graph:

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Related activities: Enzymes, Enzyme Reaction RatesRA 2

Enzyme activity is often influenced by the presence of other chemicals. Some of these can enhance an enzyme’s activity. Called cofactors, they are a nonprotein component of an

enzyme and may be organic molecules (called coenzymes) or inorganic ions (e.g. Ca2+, Zn2+). Enzymes may also be deactivated, temporarily or permanently, by enzyme inhibitors.

Enzyme Cofactors and Inhibitors

Types of Enzyme

Enzyme comprisesonly protein,

e.g. lysozyme

Enzyme

Competitiveinhibitor blocksthe active site

Competitiveinhibitor

Reversible Enzyme Inhibitors

No inhibition

Prosthetic group requiredContains apoenzyme (protein)

plus a prosthetic group,e.g. flavoprotein + FAD

Active site

Apoenzyme

Prosthetic groupis more or lesspermanentlyattached

Coenzyme requiredContains apoenzyme (protein)plus a coenzyme (non-protein)e.g. dehydrogenases + NAD

Active site

Apoenzyme

Coenzymebecomesdetached afterthe reaction

Protein-only enzymes Conjugated protein enzymes

Active site

enzyme

Nearly all enzymes are made ofprotein, although RNA has beendemonstrated to have enzymaticproperties. Some enzymes consistof just protein, while others requirethe addition of extra components tocomplete their catalytic properties.These may be permanently attachedparts called prosthetic groups, ortemporar i ly at tached p ieces(coenzymes) that detach after areaction, and may participate withanother enzyme in other reactions.

Enzyme

Substrate

Good fitS

S

Allosteric enzymeinhibitor

The substratecannot bind tothe active site

Enzyme

Noncompetitiveinhibitor

Active siteis distorted

S

Noncompetitiveinhibitor

Enzyme

Noncompetitiveinhibitor

The substrate binds to theactive site but the speedof the reaction is slowed.

Enzyme inhibitors may be reversible or irreversible. Reversible inhibitors are used tocontrol enzyme activity. There is often an interaction between the substrate or end productand the enzymes controlling the reaction. Buildup of the end product or a lack of substratemay deactivate the enzyme. This deactivation may take the form of competitive (competesfor the active site) or noncompetitive inhibition. While noncompetitive inhibitors have theeffect of slowing down the rate of reaction, allosteric inhibitors block the active sitealtogether and prevent its functioning.

Some heavy metals, such as arsenic (As),cadmium (Cd), and lead (Pb) act asirreversible inhibitors. They bind stronglyto the sulfhydryl (-SH) groups of a proteinand destroy catalytic activity. Most, includingarsenic (above), act as noncompetitiveinhibitors. Mercury (Hg) is an exceptionbecause it is a competitive inhibitor, bindingto the sulfhydryl group in the active site ofthe papain enzyme. Heavy metals areretained in the body and lost slowly.

Irreversible Inhibitors (Poisons)

Active siteis distorted

Arsenic bindsand alters theactive site

Lipothiamidepyrophosphatase

enzyme

As

Substrate cannot bind

1. Describe the general role of cofactors in enzyme activity:

2. (a) Name four heavy metals that are toxic to humans:

(b) Explain in general terms why these heavy metals are toxic to life:

3. There are many enzyme inhibitors that are not heavy metals (e.g. those found in some pesticides).

(a) Name a common poison that is an enzyme inhibitor, but not a heavy metal:

(b) Try to find out how this poison interferes with enzyme function. Briefly describe its effect on a named enzyme:

4. Explain the difference between competitive and noncompetitive inhibition:

5. Explain how allosteric inhibitors differ from other noncompetitive inhibitors:

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The Chem

istry of Life

Related Activities: The Biochemistry of Photosynthesis, The Biochemistry of Respiration RA 3

Metabolic Pathways

MelaninThyroxine

PhenylketonuriaProtein

AlbinismCretinism

Tyrosinosis

Alkaptonuria

Phenylpyruvicacid

Phenylalaninehydroxylase

Trans-aminase

Hydroxyphenyl-pyruvic acid oxidase

Homogentisicacid oxidase

Faulty enzyme causes:

Proteins are broken down torelease free amino acids, oneof which is phenylalanine.

Faulty enzyme causes:

Faulty enzyme causes buildup of:

Faulty enzyme causes:Faulty enzymes cause:

Symptoms:Mental retardation, light skin colour,excessive muscular tension andactivity, mousy body odour, eczema.

Symptoms:Complete lack of melanin in tissues,including skin, hair, and eyes (above).

Symptoms:Chronic liver and kidney disease orearly death from liver failure.

Symptoms:Dark urine, pigmentation of cartilageand other connective tissues. In lateryears, arthritis.

Symptoms:Dwarfism, mental retardation,low levels of thyroid hormones,retarded sexual development,yellow skin colour.

This in turncauses:

Tyrosinasea series ofenzymes

Phenylalanine

Tyrosine

Hydroxyphenylpyruvicacid

Homogentisicacid

Maleylacetoaceticacid

Carbondioxide

andwater

A Metabolic Pathway

The metabolism of the essential amino acid phenylalanine is awell studied metabolic pathway. The first step is carried out by aliver enzyme called phenylalanine hydroxylase, which convertsphenylalanine to the amino acid tyrosine. Tyrosine, in turn, througha series of intermediate steps, is converted into the skin pigmentmelanin and other substances. If phenylalanine hydroxylase isabsent, phenylalanine is converted (in part) into phenylpyruvicacid, which accumulates, together with phenylalanine, in thebloodstream. Phenylpyruvic acid and phenylalanine are central

nervous system toxins and produce some of the symptoms of thegenetic disease phenylketonuria. Other defects in the tyrosinepathway are also known. As indicated above, absence of enzymesoperating between tyrosine and melanin, is a cause of albinism.Tyrosinosis is a rare defect that causes hydroxyphenylpyruvicacid to accumulate in the urine. Alkaptonuria causes pigmentationto appear in the cartilage, and produces symptoms of arthritis. Adifferent block in another pathway from tyrosine produces thyroiddeficiency leading to goiterous cretinism (due to lack of thyroxine).

Case Study: The Metabolism of Phenylalanine

Gene A Gene B

Expression of Gene B (by proteinsynthesis) produces enzyme B

Precursorchemical

Intermediatechemical

Enzyme A Enzyme B

End product

Enzyme A transforms theprecursor chemical into theintermediate chemical byaltering its chemical structure

Enzyme B transforms theintermediate chemical intothe end product

Expression of Gene A (by proteinsynthesis) produces enzyme A

Pho

to: m

s.do

nna

Metabolism is all the chemical activities of life. The myriad enzyme-controlled metabolic pathways that are described as metabolism form a tremendously complex network that is necessary in order to 'maintain' the organism. Errors in the step-

wise regulation of enzyme-controlled pathways can result in metabolic disorders that in some cases can be easily identified. An example of a well studied metabolic pathway, the metabolism of phenylalanine, is described below.

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1. Using the metabolism of phenyalanine as an example, discuss the role of enzymes in metabolic pathways:

2. Identify three products of the metabolism of phenylalanine:

3. Identify the enzyme failure (faulty enzyme) responsible for each of the following conditions:

(a) Albinism:

(b) Phenylketonuria:

(c) Tyrosinosis:

(d) Alkaptonuria:

4. Explain why people with phenylketonuria have light skin colouring:

5. Discuss the consequences of disorders in the metabolism of tyrosine:

6. The five conditions illustrated in the diagram are due to too much or too little of a chemical in the body. For each condition listed below, state which chemical causes the problem and whether it is absent or present in excess:

(a) Albinism:

(b) Phenylketonuria:

(c) Cretinism:

(d) Tyrosinosis:

(e) Alkaptonuria:

7. If you suspected that a person suffered from phenylketonuria, how would you test for the condition if you were a doctor:

8. The diagram at the top of the previous page represents the normal condition for a simple metabolic pathway. A starting chemical, called the precursor, is progressively changed into a final chemical called the end product.

Consider the effect on this pathway if gene A underwent a mutation and the resulting enzyme A did not function:

(a) Name the chemicals that would be present in excess:

(b) Name the chemicals that would be absent:

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