Chapter 3Chapter 3Proteins and Enzymes (Chapter 7)

Protein Structure – determined by Protein Structure – determined by

foldingfolding• Can be globular (spherical) or fibrous

(long fibers)• Proteins fold because of interactions

between R groupso The structure directly determines its function

Four levels of protein Four levels of protein structurestructure

• Primary – sequence of amino acids

• Secondary – coils or folds in backbone

• Tertiary – interactions between R groups

• Quaternary – more than 1 polypeptide subunit

Fig. 5-21a

Amino acidsubunits

+H3N Amino end

25

20

15

10

5

1

Primary Structure

Secondary – coils or Secondary – coils or folds in backbonefolds in backbone

• H bonds between the backbone (not the R groups)

• helix – a coil

• pleated sheet – folded structure

Tertiary - interactions between R Tertiary - interactions between R

groupsgroups• Hydrophobic

interactions – nonpolar amino acids end up clustered in centero Van der Waals

• Hydrogen Bonds – polar amino acids H bond

Polypeptidebackbone

Hydrophobicinteractions andvan der Waalsinteractions

Hydrogenbond

Tertiary - interactions between R Tertiary - interactions between R

groupsgroups• Ionic Bonds –

positively and negatively charged aas bond

• Disulfide bridges – covalent bonds of two cysteines (–SH)

Polypeptidebackbone

Disulfide bridge

Ionic bond

Quaternary – more Quaternary – more than 1 polypeptide than 1 polypeptide

subunitsubunit• Polypeptides

with tertiary structure are aggregatedo Example -

hemoglobin

β Chains

HemeIron

α Chains

Hemoglobin

Denaturation - Denaturation - unravelingunraveling

• Caused by:o High or low pHo Increased salt concentrationo High temps

EnzymesEnzymes

• catalytic proteins• speed up metabolic

reactions by lowering energy barriers

• not consumed or changed

EnzymesEnzymes• substrate – the reactant

that an enzyme acts on• enzyme-substrate

complex: the enzyme bound to its substrate

• active site – the region on the enzyme where the substrate binds

• induced fit – the way the substrate fits into the active site (the enzyme changes shape slightly)

Activation Energy (EActivation Energy (EAA) )

• needed to start a chemical reactiono heat from the

surroundings

Enzymes Lower the EEnzymes Lower the EAA BarrierBarrier

Enzyme ActivityEnzyme Activity

• Lower an EA barrier by:o Orienting substrates

correctlyo Straining substrate bondso Providing a favorable

microenvironmento Covalently bonding to the

substrate

• Affected by:o temperature o pHo chemicals that

specifically influence the enzyme

Enzyme ActivityEnzyme Activity

Enzymes and Enzymes and BiotechnologyBiotechnology

• Human babies are born with lactase, an enzyme that breaks down lactose found in milk

• Naturally, as humans age they become increasingly lactose intolerant as they stop producing lactase

• Some cultures have higher percentages of people who are lactose intolerant (Asia), some lower percentages (Europe)

• Lactase is produced on large scales to create lactose-free products

Enzymes and Enzymes and BiotechnologyBiotechnology

EnzymeEnzyme InhibitorsInhibitorsCompetitive inhibitors

• Bind to the active site

• Compete with the substrate

Competitive Example:Competitive Example:• Ethylene glycol:

antifreezeo Ethanol is used to treat

ethylene glycol poisoning

o Reversible inhibition

Ethylene glycol Ethylene glycol Products formed Products formed

ethanol ethanol (inhibitor)(inhibitor)

Cause irreversible damage to the Cause irreversible damage to the kidneyskidneys

Cause irreversible damage to the Cause irreversible damage to the kidneyskidneys

Competitive Example:Competitive Example:• Sulfanilamide: antibiotic

o similar structure to para-aminobenzoic acid (PABA), (pathway for folic acid)

o IRREVERSIBLE COMPETITIVE INHIBITION

PABAPABA Folic acidFolic acid

Sulphanilamide (inhibitor)Sulphanilamide (inhibitor) NO Folic acid formation after inhibitionNO Folic acid formation after inhibition

EnzymeEnzyme InhibitorsInhibitorsNoncompetitive inhibitors

• Bind to another part of an enzyme

• Cause the enzyme (active site) to change shape

Noncompetitive Noncompetitive Example:Example:

Morphine• Binds to a site other

than the active site of the enzyme Nitric oxide synthase

• The enzyme stays inhibited

Arginine Arginine Nitric Nitric oxideoxide

CitrullineCitrullineNitric oxide synthaseNitric oxide synthase

Opioids ( morphine) in

hibit NOS

Noncompetitive Noncompetitive Example:Example:

Cyanide (CN-)• Attaches to the –SH

group of an enzyme CYTOCHROME C OXIDASE

• results in the inhibition of cellular respiration!!!

OXYGEN OXYGEN

WATERWATER

Cytochrome c oxidaseCytochrome c oxidase

CNCN- - Cya

nide

Cyanid

e

FeedbackFeedback InhibitionInhibition• The end product of a

metabolic pathway shuts down the pathway

• Prevents wasting resources