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عید سعید قربان بر شما مبارک. یلدای زیبا هم همینطور!. In the Name of Allah ENZYMES:. TUMS. … Make Life on Earth Possible Abolfazl Golestani, PhD. An Important Question:. Why should we as medical students, study and learn about the ENZYMS?

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slide1

عید سعید قربان بر شما مبارک

یلدای زیبا هم همینطور!

slide2

In the Name of Allah

ENZYMES:

TUMS

…Make Life on Earth Possible

Abolfazl Golestani, PhD

an important question
An Important Question:
  • Why should we as medical students, study and learn about the ENZYMS?
  • For answer go to slide No. 55

Enzymes; by: Dr. Abolfazl Golestani, PhD

chemical reaction
Chemical reaction

Catalyst

AB

Product(s)

Reactant(s)

Catalyst

A +B B + C

  • Catalysts
  • Increase the rate of a reaction
  • Are not consumed in the reaction
  • Can act repeatedly

Heat

Acid Base

Metals

What are some of the known catalysts?

Enzymes; by: Dr. Abolfazl Golestani, PhD

enzyme is either a pure protein or may require a non protein portion
Enzyme is either a pure protein or may require a non-protein portion

Apoenzyme = protein portion

Apoenzyme + non-protein part = Holoenzyme

According to Holum, the non-protein portion may be:

  • A coenzyme - a non-protein organic substance which is loosely attached to the protein part
  • A prosthetic group - an organic substance which is firmly attached to the protein or apoenzyme portion
  • A cofactor - these include K+, Fe++, Fe+++, Cu++, Co++, Zn++, Mn++, Mg++, Ca++, and Mo+++

Enzymes; by: Dr. Abolfazl Golestani, PhD

basic enzyme reactions
Basic enzyme reactions

S + E  E + P

S = Substrate P = Product E = Enzyme

Swedish chemist Savante Arrhenius in 1888 proposed:

Substrate and enzyme form some intermediate known as theEnzyme-Substrate Complex (ES):

S + E  ES

ES  P + E

Binding step

Catalytic step

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide7

There are two models of enzyme substrate interaction

1. Lock and key model; Emil Fischer (1890)

  • The active site:
  • Substrate Binding Site
  • Catalytic Site

2. Induced fit model; Daniel Koshland (1958)

Enzymes; by: Dr. Abolfazl Golestani, PhD

induced fit in carboxypeptidase a
Induced fit in Carboxypeptidase A

Three amino acids are located near the active site (Arg 145, Tyr 248, and Glu 270)

Enzymes; by: Dr. Abolfazl Golestani, PhD

enzyme substrate complex is transient

S

E

Enzyme-Substrate complex is transient

S + E P + E

When the enzyme unites with the substrate, in most cases the forces that hold the enzyme and substrate are non-covalent.

Binding forces of substrate are:

  • Ionic interactions: (+)•••••(-)
  • Hydrophobic interactions: (h)•••••(h)
  • H-bonds: O-H ••••• O, N-H ••••• O, etc.
  • van der Waals interactions

Enzymes; by: Dr. Abolfazl Golestani, PhD

some important characteristics of enzymes
Some important characteristics of enzymes

-Potent (high catalytic power) High reaction rates

They increase the rate of reaction by a factor of 103-1012

-Efficient (high efficiency)

catalytic efficiency is represented by Turnover number:

moles of substrate converted to product per second per mole of the active site of the enzyme

-Milder reaction conditions Enzymatically catalyzed reactions occur at mild temperature, pressure, and nearly neutral pH (i.e. physiological conditions)

Enzymes; by: Dr. Abolfazl Golestani, PhD

some important characteristics of enzymes cont
Some important characteristics of enzymes, cont.

-Specific (specificity)

Substrate specific

Reaction Specific

Stereospecific

-Capacity for regulation

Enzymes can be activated or inhibited so that the rate of product formation responds to the needs of the cell

-Location within the cell

Many enzymes are located in specific organelles within the cell. Such compartmentalization serves:

to isolate the reaction substrate from competing reactions,

to provide a favorable environment for the reaction, and

to organize the thousands of enzymes present in the cell

into purposeful pathways.

Enzymes; by: Dr. Abolfazl Golestani, PhD

specificity
Specificity

Substrate Specificity

  • Absolute specificity: For example Urease
  • Functional Groupspecificity: For example OH, CHO, NH2.
  • Linkage specificity: For example Peptide bond.

Reaction specificity

  • Yields are nearly 100%
  • Lack of production of by-products
  • Save energy and prevents waste of metabolites

Stereospecificity

  • Enzymes can distinguish between enantiomers and isomers

Enzymes; by: Dr. Abolfazl Golestani, PhD

enzymes requiring metal ions as cofactors
Enzymes requiring metal ions as cofactors

Enzymes; by: Dr. Abolfazl Golestani, PhD

many vitamins are coenzyme precursors
Many vitamins are coenzyme precursors

Enzymes; by: Dr. Abolfazl Golestani, PhD

methods for naming enzymes nomenclature
Methods for naming enzymes (nomenclature)
  • Very old method: Pepsin, Renin, Trypsin
  • Old method: Protease,Lipase,Urease
  • Systematic naming (EC = Enzyme Commission number):
  • The name has two parts:
  • The first part: name of substrate (s)
  • The second part: ending in –ase, indicates the type of reaction.

Additional information can follow in parentheses:

  • L-malate:NAD+ oxidoreductase (decarboxylating)

Enzymes; by: Dr. Abolfazl Golestani, PhD

each enzyme has an ec number e nzyme c ommission number
Each enzyme has anEC number = Enzyme Commission number
  • EC number consists of 4 integers:
  • The 1st designates to which of the six major classes an enzyme belongs
  • The 2nd integer indicates a sub class, e.g. type of bond
  • The 3rdnumber is a subclassification of the bond type or the group transferred in the reaction or both (a subsubclass)
  • The 4th number is simply a serial number

Enzymes; by: Dr. Abolfazl Golestani, PhD

there are six functional classes of enzymes
There are six functional classes of enzymes

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide19

EC Classification

Class

Subclass

Sub-subclass

Serial number

Enzyme Nomenclature and Classification

Enzymes; by: Dr. Abolfazl Golestani, PhD

example of enzyme nomenclature
Example of Enzyme Nomenclature
  • Common name(s):

Invertase, sucrase

  • Systematic name:

-D-fructofuranoside fructohydrolase

(E.C. 3.2.1.26)

  • Recommended name:

-fructofuranosidase

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide21
Kinetic

Enzyme kinetics

Enzymes; by: Dr. Abolfazl Golestani, PhD

energy barrier free energy of activation
Energy barrier = Free Energy of Activation

X T* Y

T=Transition state

(Ea)

Thermodynamics:

Type (Exergonic or Endergonic)

Kinetics:

How fast the reaction will proceed

Enzymes; by: Dr. Abolfazl Golestani, PhD

enzyme stabilizes transition state
Enzyme Stabilizes Transition State

What’s the difference? Many enzymes function by lowering the activation energy of reactions.

Enzymes; by: Dr. Abolfazl Golestani, PhD

Adapted from Alberts et al (2002) Molecular Biology of the Cell (4e) p.166

slide24
عید سعید و عظیم غدیر بر شما مبارک

ميلاد حضرت امام هادي (ع) را تهنيت مي گويم،

میلاد حضرت مسیح (ع) را هم همین طور!

e a activation energy a barrier to the reaction
EA = Activation energy; a barrier to the reaction

Can be overcome by adding energy.......

......or by catalysis

Enzymes; by: Dr. Abolfazl Golestani, PhD

enzymes are complementary to transition state
Enzymes Are Complementary to Transition State

X

If enzyme just binds substrate

then there will be no further reaction

Enzyme not only recognizes substrate,

but also induces the formation of transition state, see also Enz01

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide27

Active Site Is a Deep Buried Pocket

Why energy required to reach transition state

is lower in the active site?

It is a magic pocket

(1) Stabilizes transition

+

(2) Expels water

CoE

(2)

(1)

(3) Reactive groups

(4)

-

(4) Coenzyme helps

(3)

Enzymes; by: Dr. Abolfazl Golestani, PhD

Juang RH (2004) BCbasics

slide28

Active Site Avoids the Influence of Water

+

-

Preventing the influence of water sustains the formation of stable ionic bonds

Enzymes; by: Dr. Abolfazl Golestani, PhD

Adapted from Alberts et al (2002) Molecular Biology of the Cell (4e) p.115

enzyme reaction mechanism
Enzyme Reaction Mechanism
  • Consider for example the mechanism of Chymotrypsin:
  • Enz06
  • Enz07

Enzymes; by: Dr. Abolfazl Golestani, PhD

modes of rate enhancement
Modes of rate enhancement
  • Facilitation of Proximity
    • Increase the Effective concentration
    • Hold reactants near each other in proper orientation
  • Strain, Molecular Distortion, and Shape Change
    • Put a strain on susceptible bonds
  • General Acid –Base Catalysis
    • Transfer of a proton in the transition state
  • Covalent Catalysis
    • Form covalent bond with substrate destabilization of the substrate

Enzymes; by: Dr. Abolfazl Golestani, PhD

factors affecting rate of enzyme reactions
Factors Affecting Rate of Enzyme Reactions
  • Temperature
  • pH
  • Enzyme concentration [E]
  • Substrate concentration [S]
  • Inhibition
  • Regulation (Effectors)

Enzymes; by: Dr. Abolfazl Golestani, PhD

1 optimum temperature
1- Optimum Temperature
  • Little activity at low temperature (low number of collisions)
  • Rate increases with temperature (more successful collisions); rate doubles for every 10°C increase in temperature
  • Most active at optimum temperatures (usually 37 oC in humans)
  • Enzymes isolated from thermophilic organisms display maxima around 100 °C
  • Enzymes isolated from psychrophilic organisms display maxima around 10 °C.
  • Activity lost with denaturation at high temperatures

Enzymes; by: Dr. Abolfazl Golestani, PhD

2 optimum ph
2- Optimum pH
  • Effect of pH on ionization of active site
  • Effect of pH on enzyme denaturation
  • Each enzyme has an optimal pH (~ 6 - 8 )
    • Exceptions :

digestive enzymes in the stomach (pH 2)

digestive enzymes in the intestine (pH 8)

Enzymes; by: Dr. Abolfazl Golestani, PhD

3 enzyme concentration
3- Enzyme concentration
  • The Rate (v) of reaction Increases proportional to the enzyme concentration [E] ([S] is high)

Enzymes; by: Dr. Abolfazl Golestani, PhD

4 substrate concentration
4- Substrate concentration
  • When enzyme concentration is constant, increasing [S] increases the rate of reaction, BUT
  • Maximum activity reaches when all E combines with S (when all the enzyme is in the ES form)

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide36

0

1

2

3

4

5

6

7

8

80

60

40

20

0

Product (v)

0 2 4 6 8

Substrate (mmole) [S]

Enzyme

Velocity

Curve, see also Enz02

S

+

E

P

(in a fixed period of time)

Constant [E]

Enzymes; by: Dr. Abolfazl Golestani, PhD

Juang RH (2004) BCbasics

slide37
بسم الله الرحمن الرحیم

Enzymes

3rd part

Enzymes; by: Dr. Abolfazl Golestani, PhD

michaelis menten equation

K+1

k2

S

E

k-1

maximal velocity, Vmax

0.5Vmax

Km

Michaelis-Menten Equation

S

E

P

Enzymes; by: Dr. Abolfazl Golestani, PhD

mm equation derivation steady state
MM Equation Derivation (steady state)

Enzymes; by: Dr. Abolfazl Golestani, PhD

practical summary v max and k m
Practical Summary - Vmax and Km
  • Vmax
    • How fast the reaction can occur under ideal circumstances
  • Km
    • Range of [S] at which a reaction will occur
    • Binding affinity of enzyme for substrate
      • LARGER Km  the WEAKER the binding affinity

Enzymes; by: Dr. Abolfazl Golestani, PhD

practical summary cont
Practical Summary, cont.

Enzymes; by: Dr. Abolfazl Golestani, PhD

practical summary cont1
Practical Summary; cont.
  • Kcat/Km
    • Practical idea of the catalytic efficiency, i.e. how often a molecule of substrate that is bound reacts to give product

Enzymes; by: Dr. Abolfazl Golestani, PhD

order of reaction
Order of Reaction
  • When [S] << Km

vo = (Vmax/Km )[S]

2. When [S] = Km

vo = Vmax/2

3. When [S] >> Km

vo = Vmax

zero order

Mixed order

2

First order

Enzymes; by: Dr. Abolfazl Golestani, PhD

importance of v i in measurement of enzyme activity

k1

k2

S

E

k-1

Importance of Viin Measurement of Enzyme Activity

S

E

P

  • Working with vo minimizes complications with
  • reverse reactions
  • product Inhibition

The rate of the reaction catalyzed by an enzyme

in a sample is expressed in Units.

Units = V = activity = Micromoles (mol; 10-6 mol or ….),

of substrate reacting or product produced per min.

It is better to measure it at linear part of the curve

Enzymes; by: Dr. Abolfazl Golestani, PhD

lineweaver burk plot

1

vo

vo

1

Vmax

- 1

Km

1/S

S

Lineweaver-Burk plot

1/2

Km

Direct plot

Double reciprocal plot

Juang RH (2004) BCbasics

Enzymes; by: Dr. Abolfazl Golestani, PhD

allosteric enzymes
Allosteric Enzymes
  • Why the sigmoid shape?
  • Allosteric enzymes are multi-subunit enzymes, each with an active site
  • They show a cooperative response to substrates
  • See Enz13

hyperbolic curve; Michaelis-Menten kinetics

Sigmoidal curve

Enzymes; by: Dr. Abolfazl Golestani, PhD

irreversible inhibition enzyme stops working permanently
IrreversibleInhibition=Enzyme Stops Working Permanently
  • Destruction of enzyme
  • Irreversible Inhibitor=forms covalent bonds to E

(inactive E)

Examples:

    • Diisopropylfluorophosphate
      • inhibits acetylcholine esterase
      • binds irreversibly to –OH of serine residue
    • Cyanide and sulfide
      • Inhibit cytochrome oxidase
      • bind to the iron atom
    • Fluorouracil
      • inhibits thymidine synthase (suicide inhibition - metabolic product is toxic )
    • Aspirin
      • Inhibits prostaglandin synthase
      • acylates an amino group of the cyclooxygenase

Enzymes; by: Dr. Abolfazl Golestani, PhD

reversible inhibition temporary decrease of enzyme function
Reversible Inhibition=Temporary Decrease of Enzyme Function
  • Three types based on “how increasing [S] affects degree of inhibition”:
    • Competitive: degree of inhibition decreases
    • Non-competitive: degree of inhibition is unaffected
    • Anti- or Uncompetitive: degree of inhibition increases
  • The Lineweaver-Burk plot is useful in determining the mechanisms of actions of various inhibitors, see Enz04

Enzymes; by: Dr. Abolfazl Golestani, PhD

the effects of enzyme inhibitors
The Effects of Enzyme Inhibitors

Enzymes; by: Dr. Abolfazl Golestani, PhD

example
Example
  • When a slice of apple is exposed to air, it quickly turns brown. This is because the enzyme

o-diphenyl oxidase catalyzes the oxidation of phenols in the apple to dark-colored products.

  • Catechol can be used as the substrate. The enzyme converts it into o-quinone(A), which is then further oxidized to dark products.

Enzymes; by: Dr. Abolfazl Golestani, PhD

experiments
Experiments

No Inhibitor

effect of para-hydroxybenzoicacid (PHBA)

effect of phenylthiourea

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide53

I- Competitive Inhibition

EI

S

E

Kic

S + E

ES

E + P

+

I

Kmapp/Vmax

Kmapp

-1/Kmapp

CI

Competitive

Enzymes; by: Dr. Abolfazl Golestani, PhD

ii noncompetitive inhibition

EI

ESI

S

E

Kic

Kiu

S + E

ES

E + P

+

+

I

I

1/Vmaxapp

Km/Vmaxapp

0.5Vmax

II- Noncompetitive Inhibition

NCI

Noncompetitive

(mixed-type)

NCI

S

E

Enzymes; by: Dr. Abolfazl Golestani, PhD

iii uncompetitive inhibition

ESI

Kiu

S + E

ES

E + P

+

I

1/Vmaxapp

0.5Vmax

Kmapp/Vmaxapp

Kmapp

-1/Kmapp

III- Uncompetitive Inhibition

Uncompetitive

(catalytic)

UCI

S

E

Enzymes; by: Dr. Abolfazl Golestani, PhD

enzyme inhibitors in medicine
Enzyme Inhibitors in Medicine
  • Many current pharmaceuticals are enzyme inhibitors(e.g.HIV protease inhibitors for treatment of AIDS)
  • An example: Ethanol is used as a competitive inhibitor to treat methanol poisoning
  • Methanol formaldehyde (very toxic)
  • Ethanol competes for the same enzyme
  • Administration of ethanol occupies the enzyme thereby delaying methanol metabolism long enough for clearance through the kidneys

Alcohol dehydrogenase

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide57

Enzymes as diagnostic tools

Enzymes can be used as markers for

diagnosis and prognosis of disease

slide58

Some diagnostically important enzymes

Enzymes; by: Dr. Abolfazl Golestani, PhD

useful enzymes for early diagnosis of dental caries and periodontal disease
Useful enzymes for early diagnosis of dental caries and periodontal disease

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide60

Isozymes of Lactate Dehydrogenase

Isozymes:

    • Are catalitically identical (have same catalytic activity) BUT physically distinct
    • Can be detected by gel electrophoresis (different electrical charge)
    • Occur in oligomeric enzymes like lactate dehydrogenase (LDH)

In LDH

  • Protomers H and M can combine to make five different tetramers.

Enzymes; by: Dr. Abolfazl Golestani, PhD

isoenzymes of creatine kinase
Isoenzymes of Creatine Kinase
  • CK has 3 forms dimer B and M chains:
  • CK1= BB
  • CK2= MB
  • CK3=MM
  • Heart, the only tissue rich in CK2, increases 4-8 hr after chest pains- peaks at 24 hr.
  • LDH peaks 2-3 days after MI.
  • New markers:

Troponin T, Troponin I

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide62

Enzymatic control

of

Metabolic Pathways

Enzymes; by: Dr. Abolfazl Golestani, PhD

5 regulation effectors
5- Regulation (Effectors)

Effectors can be classified as follows:

  • According to type:
  • Homotropic effector: Substrate itself is the effector
  • Heterotropic effector: substance other than substrate is the effector
  • According to their effect:
  • Activators (positive effectors)
    • Increase the rate of enzyme
  • Inhibitors(negative effectors)
    • Decrease the velocity of reaction
    • Stop the enzyme
      • Irreversible
      • Reversible
        • Competitive
        • Non-competitive
        • Uncompetitive

Increase or decrease in enzyme reaction rate is reflected in the graph of V versus S

Enzymes; by: Dr. Abolfazl Golestani, PhD

metabolic pathways
Metabolic Pathways
  • A metabolic pathway is a chain of enzymatic reactions
    • Most pathways have many steps, each having a different enzyme (E1, E2, E3, E4)
    • Step by step, the initial substance used as substrate by the first enzyme is transformed into a product that will be the substrate for the next reaction
  • Metabolic regulation is necessary to:
    • maintain cell components at appropriate levels.
    • conserve materials and energy.

Enzymes; by: Dr. Abolfazl Golestani, PhD

regulation of enzyme activity
Regulation of “Enzyme Activity”
  • Regulation at transcription level (slowest)
  • Isozymes: enzymes specific for distinct tissues and developmental stages
  • Compartmentation of S, E and P
  • Specific proteolytic cleavage
  • Covalent modification

(Reversible phosphorylation or adenylation)

  • In response to metabolic products (fastest)
    • Substrate level control
    • Product Inhibition
    • Feedback control
    • Allosteric Effectors

Enzymes; by: Dr. Abolfazl Golestani, PhD

regulation at transcription level
Regulation at Transcription Level
  • Regulation of [E] by
    • Gene repression
    • Induction of genetic expression of enzyme
  • There is competition in a cell between the processes of protein synthesis and protein destruction
    • By altering these rates, one can alter the whole cell catalytic rate
  • It is rather slow

Enzymes; by: Dr. Abolfazl Golestani, PhD

b isoenzymes
B. Isoenzymes
  • Isozymes provide a means of regulation, specific to distinct tissues and developmental stages
  • Differential expression of isozymes
  • LDH (for example)
  • Preferential substrate affinity

Enzymes; by: Dr. Abolfazl Golestani, PhD

c compartmentalization of enzymes
C. Compartmentalization of enzymes

Substrates and cofactors within the cell are also compartmentalized

Examples:

  • Enzymes of glycolysis are located in the cytoplasm
  • Enzymes of citric acid cycle are in the mitochondria
  • Hydrolytic enzymes are found in the lysosome

Enzymes; by: Dr. Abolfazl Golestani, PhD

d proteolytic activation
D. Proteolytic activation

Activation of a zymogen

  • Some enzymes are secreted as inactive precursors, called zymogens.
    • Pancreatic proteases - trypsin, chymotrypsin, elastase, carboxypeptidase are all synthesized as zymogens: trypsinogen, chymotrypsinogen, proelastase and procarboypeptidase
  • Clotting factors are also part of a proteolytic cascade
  • Hormone peptides (Pro-insulin Insulin)
  • An on/off switch more than regulation

Enzymes; by: Dr. Abolfazl Golestani, PhD

e covalent modification
E. Covalent modification

Reversible phosphorylation

Phosphorylation is the most common type of modification.Two important classes of enzymes are:

  • Kinases Adda phosphate group to another protein/enzyme (phosphorylation)
    • transfer of phosphoryl group from ATP to -OH group of serine, threonine or tyrosine
  • Phosphatases Removea phosphate group from a protein/enzyme (dephosphorylation)

Enzymes; by: Dr. Abolfazl Golestani, PhD

1 control of s
1- Control of [S]
  • Concentration of substrate and product also control the rate of reaction, providing a biofeedback mechanism
  • Usually: 0.1 Km<[SPhysiologic]<10 km

Mild changes in [S]

Change in enzyme activity

Homotropic effectors – substrate itself (binding at different site other than the active site) affects enzyme activity on other substrate molecules. Most often this is a positive effector.

Enzymes; by: Dr. Abolfazl Golestani, PhD

2 product inhibition
2- Product inhibition
  • Enzyme is reversibly inhibited by the product

Example: hexokinase in the first reaction of glycolysisis inhibited by glucose-6-phosphate (G6P; the product)

glucose + ATP glucose-6-phosphate + ADP 

_

Why?

As v approaches Vmax, the product becomes significant, and can compete with the substrate for the enzyme.

The product becomes a competitive inhibitor and slows down activity of the enzyme.

Enzymes; by: Dr. Abolfazl Golestani, PhD

3 negative feedback control end product inhibition
3- Negative feedback control(end product inhibition)
  • Final product of a metabolic sequence feeds-back negatively on early steps
  • In feedback inhibition, there is a second binding site on the enzyme where the inhibitor binds, so that the inhibitor is not necessarily similar in structure to the substrate

Enz 1

Enz 2

Enz 3

Enz 4

AB C D E

_

  • What happens?
  • As the need for product E decreases, E will accumulate
  • Most efficient to inhibit at first step of the pathway, slow the first reaction so intermediates do not build up 
  • An increase in the concentration of E, leads to a decrease in its rate of production of E

Enzymes; by: Dr. Abolfazl Golestani, PhD

regulation of the metabolism feed back inhibition by the final product end product inhibition
Regulation of the metabolism, feed-back inhibition by the final product - end product inhibition

Enzymes; by: Dr. Abolfazl Golestani, PhD

4 positive feedforward control
4- Positive feedforward control
  • Earlier reactants in a metabolic sequence feed-forward positively on later steps.

+

If A is accumulating, it speeds up downstream reactions to use it up

+

Metabolism involves the complex integration of many feedback and feedforward loops

Enzymes; by: Dr. Abolfazl Golestani, PhD

4 allosteric control
4- Allosteric control
  • Allosteric activator stabilizes active "R" state
    • shift the graph to the left
  • Allosteric inhibitor stabilizes less active or inactive "T" state
    • shift the graph to the right

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide77

Multi reactant enzymes

have more than one substrate

Enzymes; by: Dr. Abolfazl Golestani, PhD

multi reactant enzymes reactancy
Multi reactant enzymes reactancy
  • Published by W. W. Cleland in1963
  • Nomenclature is based on number of substrates and products in the reaction.
  • Reactancy: the number of kinetically significant substrates or products and designated by syllables Uni, Bi, Ter, Quad.

A  P Uni Uni

A  P + Q Uni Bi

A + B  P + Q Bi Bi

A + B + C  P + Q + R + S Ter Quad

Enzymes; by: Dr. Abolfazl Golestani, PhD

multi reactant enzymes mechanism
Multi reactant enzymes mechanism
  • Sequential - if all S add to E before any P are released.
    • Sequential ordered - if S add in an obligatory order (two on; two off)
    • Sequential random - if S do not add in obligatory order (two on; two off)
  • Ping Pong - If one or more S released before all S bind
    • (one on, one off; one on, one off);
    • Note: there is some sort of modified enzyme intermediate (often covalent intermediate)

Enzymes; by: Dr. Abolfazl Golestani, PhD

random sequential example
Random sequential (example)

Enzymes; by: Dr. Abolfazl Golestani, PhD

ordered sequential example
Ordered sequential (example)

Enzymes; by: Dr. Abolfazl Golestani, PhD

ping pong or double displacement mechanism
Ping pong or double displacement mechanism

Enzymes; by: Dr. Abolfazl Golestani, PhD

double displacement example
Double displacement (example)

Enzymes; by: Dr. Abolfazl Golestani, PhD

other kinds of enzymes
Other kinds of enzymes
  • Some ribonucleoprotein enzymes have been discovered
    • The catalytic activity is in the RNA part
    • They are called Ribozymes
  • Catalytic antibodies are called Abzymes

Enzymes; by: Dr. Abolfazl Golestani, PhD

slide86
موفق باشید

Enzymes; by: Dr. Abolfazl Golestani, PhD