enzymes and metabolism

Advanced Biology

Enzymes and Metabolism

Metabolism Is the sum of an organism’s chemical

reactions Metabolic pathways begin with a specific

molecule and end with a product Each step is catalyzed by a specific enzyme

Enzyme 1 Enzyme 2 Enzyme 3

A B C D

Reaction 1 Reaction 2 Reaction 3

Startingmolecule

Product

Metabolism

Catabolic pathways Break down complex molecules into

simpler compounds Release energy

Anabolic pathways Build complicated molecules from simpler

ones Consume energy

5.1

Free Energy

Energy that is free to do work in cells (∆G)

Organisms are continually expending free energy

How is it replaced?

Where is it stored?

5.2

Reactions in Metabolism

An exergonic reaction Proceeds with a net release of free energy and

is spontaneousReactants

Products

Energy

Progress of the reaction

Amount ofenergyreleased (∆G <0)

Fre

e e

ner

gy

5.2

Reactions in Metabolism

An endergonic reaction Is one that absorbs free energy from its

surroundings and is not spontaneous

Energy

Products

Amount ofenergyreleased (∆G>0)

Reactants

Progress of the reaction

Fre

e e

ner

gy

5.2

ATP hydrolysis Can be coupled to other reactions

Endergonic reaction: ∆G is positive, reaction is not spontaneous

∆G = +3.4 kcal/molGlu Glu

∆G = - 7.3 kcal/molATP H2O+

+ NH3

ADP +

NH2

Glutamicacid

Ammonia Glutamine

Exergonic reaction: ∆ G is negative, reaction is spontaneous

P

Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/mol

How ATP Performs Work

ATP drives endergonic reactions By phosphorylation, transferring a

phosphate to other molecules

How ATP Performs Work

(c) Chemical work: ATP phosphorylates key reactants

P

Membraneprotein

Motor protein

P i

Protein moved(a) Mechanical work: ATP phosphorylates motor proteins

ATP

(b) Transport work: ATP phosphorylates transport proteinsSolute

P P i

transportedSolute

GluGlu

NH3

NH2P i

P i

+ +

Reactants: Glutamic acid and ammonia

Product (glutamine)made

ADP+

P

The three types of cellular work are powered by the hydrolysis of ATP

Enzymes

A catalyst Is a chemical agent that speeds up a

reaction without being consumed by the reaction

An enzyme Is a protein catalyst Enzymes speed up metabolic reactions

by lowering activation energy

5.3

Activation EnergyF

ree

ener

gy

Progress of the reaction

∆G < O

EAA B

C D

Reactants

A

C D

B

Transition state

A B

C D

Products

Is the initial amount of energy needed to start a chemical reaction

Exergonic Reaction

5.4

The effect of enzymes on activation energy and reaction rate

Progress of the reaction

Products

Course of reaction without enzyme

Reactants

Course of reaction with enzyme

EA

withoutenzyme

EA with enzymeis lower

∆G is unaffected by enzymeF

ree

ener

gy

5.4

Substrate Specificity of Enzymes

The substrate Is the reactant an enzyme acts on

The enzyme Binds to its substrate, forming an

enzyme-substrate complex

5.5

Enzyme Specificity The active site

Is the region on the enzyme where the substrate binds

The active site is designed to fit to a specific substrate

Substrate

Active site

Enzyme

5.5

Induced Fit Model Induced fit binding

of a substrate Brings chemical groups

of the active site into positions that allow them to catalyze the chemical reaction with the substrate

Enzyme- substratecomplex

substrate

enzyme

5.6

Induced Fit Model

Substrates

Products

Enzyme

Enzyme-substratecomplex

1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).

2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.

3 The active site (R groups of its amino acids) can lower EA and speed up a reaction by:

1. orienting substrates correctly

2. straining substrate bonds3. providing a favorable

microenvironment4. covalently bonding to the

substrate

4 Substrates are Converted intoProducts.

5 Products areReleased.

6 Active siteIs available fortwo new

substrateMole.

5.6/5.7

Effects of Temperature Each enzyme has an optimal temperature in which it

can functionOptimal temperature for

enzyme of thermophilic (heat-tolerant) bacteria

Rat

e o

f re

acti

on

0 20 40 80 100Temperature (Cº)

Optimal temperature fortypical human enzyme

5.8

Effects of pH Each enzyme has an optimal pH in which it can

function

Rat

e o

f re

acti

on

pH

Optimal pH for pepsin (stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

10 2 3 4 5 6 7 8 9

5.8

Cofactors

Cofactors Are nonprotein enzyme helpers such as

the metals iron, zinc and copper Coenzymes

Are organic cofactors and include most vitamins

5.8

Enzyme Inhibitors

Competitive inhibitors Bind to the

active site of an enzyme and compete with the substrate

Competitive inhibition

A competitiveinhibitor mimics the

substrate, competingfor the active site.

Competitiveinhibitor

A substrate canbind normally to the

active site of anenzyme.

Substrate

Active site

Enzyme

Normal binding

5.8

Enzyme Inhibitors

Noncompetitive inhibitors Bind to another

part of an enzyme causing a change in the shape of the active site

A noncompetitiveinhibitor binds to the

enzyme away fromthe active site, altering

the conformation ofthe enzyme so that its

active site no longerfunctions.

Noncompetitive inhibitor

Noncompetitive inhibition5.8

Enzyme Regulation

Regulation of enzyme activity helps control metabolism

Allosteric enzyme regulation Is the term used to describe any case in which a

protein’s function at one site is affected by binding of a regulatory molecule at another site

5.9

Allosteric Regulation Many enzymes

change shape when regulatory molecules bind to specific sites, affecting function

Non-functional active site

Stabilized inactiveform

Allosteric activatorstabilizes active formAllosteric enzyme

with four subunits Active site

Regulatorysite

Active formActivator

Stabilized active form

Allosteric activatorstabilizes active form

InhibitorInactive form5.9

Allosteric Regulation

Cooperativity Is a form of

allosteric regulation that can amplify enzyme activity

Binding of one substrate molecule toactive site of one subunit locks all subunits in active conformation.

Substrate

Inactive form Stabilized active form

5.9

Feedback Inhibition

In feedback inhibition The end product of a metabolic pathway

shuts down the pathway

5.9

Feedback inhibition

5.9

The end product binds to the enzyme inhibiting its ability to catalyze the reaction with the initial substrate

This is very common in metabolic pathways as a form of regulation