1Pages 96 - 103

AN INTRODUCTION AN INTRODUCTION TO METABOLISMTO METABOLISM

EnzymesEnzymes1.1. Enzymes speed up metabolic reactions by lowering energy barriers.Enzymes speed up metabolic reactions by lowering energy barriers.

2.2. Enzymes are substrate specific.Enzymes are substrate specific.

3. The active site is an enzyme’s catalytic center.3. The active site is an enzyme’s catalytic center.

4. A cell’s physical and chemical environment affects enzyme activity.4. A cell’s physical and chemical environment affects enzyme activity.

ENZYMES: ENZYMES: A protein with catalytic A protein with catalytic

properties due to its power properties due to its power of specific activationof specific activation

Hydrolysis of sucrose (Hydrolysis of sucrose (table sugar))

Glucose + FructoseGlucose + Fructose SucroseSucroseDehydrationDehydration

Hydration Hydration (H(H22O)O)

SucraseSucraseGlucose + FructoseGlucose + Fructose

Hydrolysis of sucrosesucrose in the presence of in the presence of SucraseSucrase results in its two monosaccharide components.

This process include:This process include:

1- Breaking the bond between Glucose and Fructose;1- Breaking the bond between Glucose and Fructose;

2- Then, forming new bonds with 2- Then, forming new bonds with HH++ and and OHOH-- from water from water

This process consumes This process consumes تستهلكتستهلك energy (energy (Activation Energy;

EEAA))

A A catalystcatalyst حفز is a chemical agent that changes the rate of a is a chemical agent that changes the rate of a الُمحفزالُمreaction without being consumed reaction without being consumed ستهلك ُي أن ستهلك دون ُي أن .by the reaction.by the reaction دون

An enzyme is a catalytic protein.An enzyme is a catalytic protein.

Chemical reactions between molecules involve both Chemical reactions between molecules involve both bond breakingbond breaking and and bond formingbond forming..

To hydrolyze (To hydrolyze (hydrationhydration) ) sucrosesucrose, the bond between glucose and , the bond between glucose and fructose must be broken fructose must be broken viavia hydrolysis in the presence of hydrolysis in the presence of sucrasesucrase ( (the catalyst).).

Enzymes speed up metabolic reactions Enzymes speed up metabolic reactions by lowering energy barriers by lowering energy barriers الطاقة حواجز

SucraseSucrase

CatalystCatalyst:: It is a chemical agent that accelerate the reaction without being It is a chemical agent that accelerate the reaction without being consumed by the reaction.consumed by the reaction.

Enzyme is a Enzyme is a catalytic proteincatalytic protein بروتين بروتين

محفز/ محفز/مساعد مساعد Enzyme is a Enzyme is acatalytic proteincatalytic protein بروتين بروتين

محفز/ محفز/مساعد مساعد

Activation Energy: Activation Energy: It is the minimum amount of energy needed to start a reaction. It is It is the minimum amount of energy needed to start a reaction. It is the amount of energy needed for the reaction (the amount of energy needed for the reaction (between enzyme & substrate) between enzyme & substrate) to complete (to complete (to break the bonds).).Raising the temperature for these reactions to complete will either Raising the temperature for these reactions to complete will either denaturedenature the compounds or the compounds or killkill the cell. the cell.

Thus, organisms must therefore use a Thus, organisms must therefore use a catalystcatalyst محفز محفز عامل ..عامل

Enzymes and Activation EnergyEnzymes and Activation Energy

Enzyme is a specific Enzyme is a specific متخصصمتخصص catalyst for specific reactants catalyst for specific reactants at any time in the cell (at any time in the cell (e.g. Sucrase for only Sucrose).).

5

Activation energy:Activation energy: is the amount of is the amount of energy necessary to push the energy necessary to push the reactants over an energy barrier.reactants over an energy barrier.

At the transition state, the molecules At the transition state, the molecules

are at an are at an

unstable point.unstable point.

The difference between free energy The difference between free energy

of the products of the products

and the free energy and the free energy

of the reactants is the delta of the reactants is the delta

G.G.

Enzyme Enzyme can increase the rate of

reactions by lowering by lowering

EEAA. .

The transition state can then The transition state can then

be reached even be reached even

at moderate at moderate

temperatures temperatures. .

• The The substrate substrate هضُمها الُمطلوب هضُمها الُمادة الُمطلوب is a reactant which binds to an is a reactant which binds to an الُمادةenzyme.enzyme.

• When a substrate binds to an enzyme, the enzyme catalyzes When a substrate binds to an enzyme, the enzyme catalyzes ُيسهلُيسهل the the conversion conversion تحوُيلتحوُيل of the substrate to the product of the substrate to the product البنائية البنائية مكوناتها ..مكوناتها– Sucrase (Sucrase (catalyst) is an enzyme that binds to sucrose () is an enzyme that binds to sucrose (substrate) and ) and

breaks the disaccharide into fructose and glucose (breaks the disaccharide into fructose and glucose (products).).

Enzymes are substrate specificEnzymes are substrate specific

SubstrateSubstrate Product (s)Product (s)Enzyme (Enzyme (a catalysta catalyst))

Sucrose + HSucrose + H22OOSucraseSucrase

Glucose + FructoseGlucose + Fructose

Specificity of enzyme Specificity of enzyme اإلنزُيم اإلنزُيم تخصصية refers to the shape of its refers to the shape of its تخصصية

Active SiteActive Site النشط النشط الُمركز the surfacethe surface of of ُيُـناسبُيُـناسب intointo which which fits fits الُمركزthe substrate.the substrate.

The The active siteactive site النشط النشط الُمكان on the on the الجيبالجيبof an enzymes is the grooveof an enzymes is the grooveالُمكانsurface of the enzyme into which the substrate fits.surface of the enzyme into which the substrate fits.The specificity of an enzyme is due to the fit between The specificity of an enzyme is due to the fit between بين بين التناسب the the التناسبactive siteactive site and that of the and that of the substratesubstrate..As the substrate binds, the enzyme changes shape to As the substrate binds, the enzyme changes shape to fit fit the the substratesubstrate, bringing chemical groups in position to catalyze the , bringing chemical groups in position to catalyze the reaction.reaction.

The active site is an enzyme’s catalytic centerThe active site is an enzyme’s catalytic center

Catalytic Cycle of EnzymeCatalytic Cycle of Enzyme

Active site of enzyme and Catalytic CycleActive site of enzyme and Catalytic Cycle

SucraseSucraseSucroseSucrose

GlucoseGlucose

FructoseFructoseHH22OO

1- The substrate binds to the active site of enzyme.

2- This forms an Enzyme-Substrate complex (via weak

hydrogen bonds).

3- The active site catalyses the conversion of the substrate to final products (original components) by breaking bonds.

4- The resulting products release from the enzyme.

5- The enzyme starts another reaction over and over again.

6- Thus, the enzyme can have a huge metabolic effect in the catalytic cycle.

Catalytic Cycle of EnzymeCatalytic Cycle of Enzyme

A single enzyme molecule can catalyze thousands or more reactions A single enzyme molecule can catalyze thousands or more reactions a second.a second.

Enzymes are unaffected by the reaction and are reusable Enzymes are unaffected by the reaction and are reusable استخدامها استخدامها ُيُـعاد ..ُيُـعاد

Most metabolic enzymes Most metabolic enzymes األُيضية األُيضية اإلنزُيُمات can catalyze a reaction in both can catalyze a reaction in both اإلنزُيُماتthe the forwardforward and and reversereverse direction. direction.

The actual direction depends on the relative concentrations of products The actual direction depends on the relative concentrations of products and reactants.and reactants.

Enzymes catalyze reactions in the direction of equilibrium Enzymes catalyze reactions in the direction of equilibrium التعادلالتعادل..

Enzymes lower activation energy and speed a reaction.

The rate that a specific number of enzymes converts substrates to products depends in part on substrate concentrations.

At some substrate concentrations, the active sites on all enzymes are engaged مشغولة, called enzyme saturation اإلنزُيُم يالتشبع .

12

• Changes in shape of the enzyme molecule influence the reaction Changes in shape of the enzyme molecule influence the reaction rate.rate.

• Some conditions lead to the most active conformation and lead to Some conditions lead to the most active conformation and lead to optimal rate of reaction. These factors are:-optimal rate of reaction. These factors are:-

A)- A)- Cellular factors affecting enzyme activityCellular factors affecting enzyme activity

1.1. Temperature:Temperature: has a major has a major impact on reaction rateimpact on reaction rate..

As temperature increases, As temperature increases, reaction between substrate reaction between substrate and active sites occur faster.and active sites occur faster.

However, at some point However, at some point thermal increase begins to thermal increase begins to denature the enzyme.denature the enzyme.

Each enzyme has an Each enzyme has an optimal optimal temperaturetemperature ثلىم حرارة مثلى درجة حرارة .. درجة

3. Cofactors3. Cofactors : : الُمساعدة الُمساعدة العوامل العوامل

A non-protein helpers for catalytic activity of enzymes. They bind A non-protein helpers for catalytic activity of enzymes. They bind permanently permanently دائُمادائُما to the enzyme and include two types:-to the enzyme and include two types:-

a)- Inorganica)- Inorganic cofactors,cofactors, include include zinc, iron, and copperzinc, iron, and copper..

b)- Organic cofactorsb)- Organic cofactors, include , include vitaminsvitamins or molecules derived or molecules derived from vitamins.( from vitamins.(coenzymes)

2. pH2. pH also influences the reaction rate, each enzyme has also influences the reaction rate, each enzyme has an an optimal pHoptimal pH falls between pH 6 - 8 for most falls between pH 6 - 8 for most enzymes.enzymes.

• However, digestive enzymes in the However, digestive enzymes in the stomachstomach are designed to work best are designed to work best at at pH 2pH 2 while those in the while those in the intestineintestine are optimal at are optimal at pH 8pH 8, both matching , both matching their working environments. their working environments.

14

• Competitive inhibitionCompetitive inhibition تنافس تنافس تثبيط ييتثبيط : the inhibitor binds to : the inhibitor binds to the same site the same site as the substrateas the substrate, thus prevent the enzymatic reactions., thus prevent the enzymatic reactions.

B)- Enzyme inhibitors: B)- Enzyme inhibitors: طاتB Bطات مـثـب مـثـباإلنزُيُماتاإلنزُيُمات

• NonNon--competitive inhibitioncompetitive inhibition: : ال ال تثبيط تثبيطييتنافستنافس the inhibitor binds somewhere the inhibitor binds somewhere

other than the active site,other than the active site, resulting in resulting in changing enzyme shape. Finally, changing enzyme shape. Finally, deactivate deactivate ُيُـخُمدُيُـخُمد the active sitethe active site

• Inhibitors are chemicals that reduce the rate of enzymic reactions. • The are usually specific and they work at low concentrations.• They block the enzyme but they do not usually destroy it. • Many drugs and poisons are inhibitors of enzymes in the nervous system.

The insecticide The insecticide DDTDDT is inhibitor for key enzymes is inhibitor for key enzymes of nervous system in insects results in death.of nervous system in insects results in death.

Many antibiotics (e.g. Many antibiotics (e.g. PenicillinPenicillin) inhibits ) inhibits enzymes that help bacteria to make their cell enzymes that help bacteria to make their cell walls.walls.

Activation and inhibition of Activation and inhibition of enzymes are essential for enzymes are essential for

metabolic control metabolic control

Some benefits of enzyme inhibitorsSome benefits of enzyme inhibitors

In the next lecture we will see that: