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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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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
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


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



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


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


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


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


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


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


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



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


Enzymes as diagnostic tools

Enzymes can be used as markers for

diagnosis and prognosis of disease


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


Isozymes of Lactate Dehydrogenase periodontal disease

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 periodontal disease

    • 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


    Enzymatic control periodontal disease

    of

    Metabolic Pathways

    Enzymes; by: Dr. Abolfazl Golestani, PhD


    5 regulation effectors
    5- Regulation (Effectors) periodontal disease

    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 periodontal disease

    • 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” periodontal disease

    • 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 periodontal disease

    • 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 periodontal disease

    • 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 periodontal disease

    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 periodontal disease

    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 periodontal disease

    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] periodontal disease

    • 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 periodontal disease

    • 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 periodontal disease(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 final product - end product inhibition

    • 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 final product - end product inhibition

    • 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


    Multi reactant enzymes final product - end product inhibition

    have more than one substrate

    Enzymes; by: Dr. Abolfazl Golestani, PhD


    Multi reactant enzymes reactancy
    Multi reactant enzymes reactancy final product - end product inhibition

    • 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 final product - end product inhibition

    • 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


    Enzymes; by: Dr. Abolfazl Golestani, PhD final product - end product inhibition


    Random sequential example
    Random sequential (example) final product - end product inhibition

    Enzymes; by: Dr. Abolfazl Golestani, PhD


    Ordered sequential example
    Ordered sequential (example) final product - end product inhibition

    Enzymes; by: Dr. Abolfazl Golestani, PhD


    Ping pong or double displacement mechanism
    Ping pong or double displacement mechanism final product - end product inhibition

    Enzymes; by: Dr. Abolfazl Golestani, PhD


    Double displacement example
    Double displacement (example) final product - end product inhibition

    Enzymes; by: Dr. Abolfazl Golestani, PhD


    Other kinds of enzymes
    Other kinds of enzymes final product - end product inhibition

    • 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


    موفق باشید final product - end product inhibition

    Enzymes; by: Dr. Abolfazl Golestani, PhD