Nature of enzyme catalysis

Mr. Santhosh. N M.Sc,

PG Biochemistry dept, JSSCACS college,
Mysuru.
What apparently make enzymes such
powerful catalysts???
• specificity of substrate binding.
• optimal arrangement of catalytic groups.
 Acid–Base Catalysis
Acid catalysis
•General acid catalysis is a process in which partial proton
transfer from a acid (a species that can donate Protons).

•By lowers the free energy of a reaction’s transition state.

For example, an uncatalyzed keto–enol
tautomerization reaction occurs quite slowly as a
result of the high energy of it’s carbanion like
transition state

Proton donation to the oxygen atom reduces the carbanion

character of the transition state, thereby catalyzing the
reaction.
 Base catalysis
A reaction stimulated by partial proton abstraction
by a base ,general base catalysis increases the rate.
Some reactions may be simultaneously subject to
both processes: a concerted general acid–base
catalyzed reaction.
• Ring opening can be catalyzed
by both acid and base .

• A proton will attack the ring

oxygen with subsequent ring
opening.

• The hydroxide ion will initiate

ring opening through removal
of the proton of the anomeric
hydroxyl group.
Rnase A enzyme
catalysed acid base
reaction.
Biochemically significant reactions are
susceptible to acid and/or base catalysis.
• These include the hydrolysis of peptides and esters,
the reactions of phosphate groups,tautomerizations,
and additions to carbonyl groups.

• The side chains of the amino acid residues are Asp,

Glu, His, Cys, Tyr, and Lys
 Covalent Catalysis
Covalent catalysis involves rate acceleration through
the transient formation of a catalyst–substrate
covalent bond.

1. The nucleophilic reaction between the catalyst and

the substrate to form a covalent bond by donating the
electrons.

2. The withdrawal of electrons from the reaction center

by the electrophilic catalyst.
 3) elimination
1) nucleophilic
attack

2) electrophilic
withdrawl
The primary amine-catalyzed decarboxylation of acetoacetate is
clearly an electrophilically catalyzed.

Reaction since its nucleophilic phase, Schiff base formation, is

not its rate-determining step.

The nucleophilicity of a substance is closely related to it’s basicity.

The mechanism of nucleophilic catalysis resembles that of general

base catalysis except that, instead of abstracting a proton from
the substrate, the catalyst nucleophilically attacks it so as to
form a covalent bond.
• If covalent bond formation is the rate-determining
step of a covalently catalyzed reaction, the reaction rate
tends to increase with the covalent catalyst’s basicity (pK).

• An important aspect of covalent catalysis is that the

more stable the covalent bond formed.

• A good covalent catalyst must therefore combine the

properties of high nucleophilicity and the ability to form a
good leaving group, that is, to easily reverse the bond
formation step.
Functional groups that participate in covalent
catalysis include
Imidazole moiety of His,
Thiol group of Cys,
Carboxyl function of Asp, and
Hydroxyl group of Ser.

Coenzymes, most notably

Thiamine pyrophosphate (Thiazolium ring) and
pyridoxal phosphate function.
 Metal Ion Catalysis
About one-third of all known enzymes require the presence
of metal ions for catalytic activity.

There are two classes

metal ion–requiring enzymes that are distinguished by the
Strengths of their ion–protein interactions:

1. Metalloenzymes contain tightly bound metal ions,

most commonly transition metal ions such as Fe2+, Fe3+,
Cu2+, Zn2+,Mn2+, or Ca2+.

2. Metal-activated enzymes loosely bind metal ions

from solution, usually the alkali and alkaline earth metal
ions Na+, K+,Mg2+, or Ca2+.
Metal ions participate in the catalytic process in three major
ways:
1. By binding to substrates so as to orient them properly for
reaction.
2. 2. By mediating oxidation–reduction reactions through
reversible changes in the metal ion’s oxidation state.
3. By electrostatically stabilizing or shielding negative charges.

Here the metal ion (Cu2+ or Ni2+), which is chelated by the

dimethyloxaloacetate, electrostatically stabilizes the developing
enolate ion of the transition state.

Most enzymes that decarboxylate oxaloacetate require a metal

ion for activity.
Metal Ions Promote Nucleophilic Catalysis via Water Ionization

A metal ion’s charge makes its bound water molecules more

acidic than free H2O and therefore a source of OH- ions even
below neutral pH’s.

For example, the water molecule of

_ +
(NH3)5Co3+(H2O) (NH3)5Co3+OH + H

Ionizes with a pK of 6.6,which is 9 pH units below the pK of free

H2O.
The resulting metal ion–bound hydroxyl group is a potent
nucleophile.
Carbonic anhydrase contains an essential Zn2 + ion
_
CO2+H2O HCO3 + H+
 2+
Carbonic anhydrase contains an essential Zn ion that lies at the
bottom of an 15-Å-deep active site cleft ,where it is tetrahedrally
coordinated by three evolutionarily invariant His side chains and
_
an O atom of either an HCO3 ion or a water molecule.
It’s begin with a water molecule bound to the protein in the Zn2+
ion’s fourth liganding position.

This Zn2+polarized H2O ionizes in a process facilitated through

general base catalysis by His 64 in its “in” conformation.

Although His 64 is too far away from the Zn2+ bound water to
directly abstract its proton, these entities are linked by two
intervening water molecules to form a hydrogen bonded network
that is thought to act as a proton shuttle.
_
The resulting Zn2+bound OH ion nucleophilically attacks the
_
nearby enzymatically bound CO2,thereby converting it to HCO3 .
Catalysis through Proximity and Orientation.
Proximity and Orientation:
Catalytic efficiency must arise from the specific physical conditions
at enzyme catalytic sites that promote the corresponding chemical
reactions.
EX:

K = 0.0018/s, and K = 0.043 /s

1 2
The imidazole group in the
intramolecular reaction behaves
as if its concentration is 24M.
Chymotrypsin
Orientation
 Orbital Steering

The rate of the reaction, is 315 times faster when R is CH3

rather than when it is H because of the greater steric
repulsions between the CH3 groups and the reacting groups.

The ring opening reactions are considerably more facile for

strained rings such as cyclopropane than for unstrained rings
such as cyclohexane.
 Entropy effect

Binding energy makes an important, and sometimes the dominant,

contribution to catalysis.

Prominent physical and thermodynamic factors contributing to G‡,

the barrier to reaction, which include

(1) a reduction in entropy, in the form of decreased freedom of

motion of two molecules in solution;

(2) The solvation shell of hydrogen-bonded water that surrounds and

helps to stabilize most biomolecules in aqueous solution;

(3) The need for proper alignment of catalytic functional groups on

the enzyme. Binding energy can be used to overcome all these
barriers .
Multisubunit Proteins
Proteins with two or more polypeptides associated noncovalently.
The individual polypeptide chains in a multisubunit protein may be
identical or different.
If a multisubunit protein have two identical unit is said to be
oligomeric, and the identical units are referred to as protomers.
Identical unit consisting of one or more polypeptide chains
Hemoglobin;
• Hemoglobin (molecular weight of 65,450) is an oligomeric, allosteric,
conjugated protein with four polypeptide chains joined by non-covalent bonds.
• The first oligomeric protein for which the three dimensional structure was
determined was hemoglobin.
• Which contains four polypeptide chains and four heme prosthetic groups, in
which the iron atoms are in the ferrous (Fe2+) state.
• The protein portion, called globin, consists of two α chains (141 residues each)
and two β chains (146 residues each).
• Two identical α chains and two identical β chains, all four held together by
noncovalent interactions. Each α subunit is paired in an identical way with a β
subunit and it’s tetramer of four polypeptide subunits or a dimer of αβ
protomers.
Hemoglobin functions:
It facilitates 02 and C02 transport, and It has an important role as a
buffer.
Binding of oxygen to hemoglobin
A single molecule of hemoglobin, binds up to four oxygen
molecules.
Hb + 402 Hb (02)4
The equation for the fractional saturation of hemoglobin would
be, Y = (P02)4
(P02)4 + Kd
The slope of a Hill plot is therefore
denoted by nH, the Hill coefficient,
which is a measure of the degree of
cooperativity.
If nH equals 1, ligand binding is not
cooperative,
nH of greater than 1 indicates
positive cooperativity and
nH of less than 1 indicates negative
cooperativity.

Hemoglobine shows positive nH=3

cooperativity.
Factors affecting the affinity of Hb for oxygen
2,3 bisphosphoglycerate (BPG), pH and
temp.

Elevated temperature, low pH and increased 2,3

BPG shift the curve to the right (decrease affinity)
which enhances unloading of O2 from Hb.

Conversely, a decrease in temperature, high pH

and a decrease in 2,3 BPG shifts the O2-Hb
dissociation curve to the left (increase affinity)
which promotes loading of O2 onto Hb.

2,3 bisphosphoglycerate has a heterotropic

effect
 The concerted model by Monod, Wyman and Changeux (MWC)
• Allosteric proteins are oligomers composed of an even number
of identical subunits.
• Each monomer in an oligomer can exist in two conformations
labeled as T (tense) and R (relaxed), which are in equilibrium.
• The binding affinities of ligand to these two conformations are
different.
• At any given time all the monomers in an oligomeric molecule
possess the same conformation.
 Sequential model by Koshland, Némethy and Filmer 
• The sequential model proposes that as ligand binds to one
subunit, there is a change in the conformtation of the subunit,
which then induces a conformational change in a contiguous
subunit.
• Unlike the concerted model, the sequential model can have
tetramers that consist of both R and T state subunits
Aspartyl transcarbamylase
E. coli ATCase (309 kD) has the subunit composition c6r6, where c and r represent
its catalytic and regulatory subunits (311 and 153 residues respectively).
The regulatory subunits allosterically reduce the activity of the catalytic subunits
in the intact enzyme.
ATCase’s substrates, carbamoyl phosphate and aspartate, each bind to a separate
domain of the catalytic subunit.
The binding of N-(phosphonacetyl)-L-aspartate (PALA) to the enzyme, which
presumably mimics the binding of both substrates, induces active site closure in a
manner that would bring them together so as to promote their reaction.
The resulting atomic shifts, up to 8 Å for some residues, trigger ATCase’s T to R
quaternary shift. Indeed, ATCase’s tertiary and quaternary shifts are so tightly
coupled through extensive inter subunit contacts that they cannot occur
independently.
low levels of PALA actually activate ATCase
by promoting its T to R transition: ATCase
has such high affinity for this unreactive
bisubstrate analog that the binding of one
molecule of PALA converts all six of its
catalytic subunits to the R state. Evidently,
ATCase closely follows the symmetry model
of allosterism.
Both the inhibitor CTP and the activator ATP bind to the same site on
the outer edge of the regulatory (r) subunit, about 60 Å away from
the nearest catalytic site. CTP binds preferentially to the T state,
increasing its stability while ATP binds preferentially to the R state,
increasing its stability.
Allosteric Transitions in Other Enzymes Resemble Those of
Hemoglobin and ATCase phosphofructokinase, fructose-1,6-
bisphosphatase, and glycogen phosphorylase.
Chymotrypsin Mechanism
Bovine pancreatic chymotrypsin (Mr 25,191) is a
protease, an enzyme that catalyzes the hydrolytic
cleavage of peptide bonds. This protease is specific for
peptide bonds adjacent to aromatic amino acid
residues (Trp, Phe, Tyr).

The reaction catalyzed by

this enzyme illustrates the
principle of transition-state
stabilization and also provides a
classic example of
general acid-base catalysis and
covalent catalysis.
Charge relay network
Aspartate (102) maintains positive charge on nitrogen.
LYSOZYME
• Lysozyme is a natural antibacterial agent
found in tears and egg whites. The hen egg
white lysozyme (Mw 14,296) is a monomer
with 129 amino acid residues.

•The structure revealed four stabilizing

disulfide bonds and a cleft containing the
active site.

•The substrate of lysozyme is peptidoglycan, a

carbohydrate found in many bacterial cell
walls, consists of glucosamine (GlcNAc), often
referred to as NAM and NAG, respectively.
Lysozyme is an enzyme that destroys bacterial cell walls.

Hydrolyzing the ß(1 - 4) glycosidic linkages from N-acetylmuramic

acid (NAM) to N-acetylglucosamine (NAG) in the alternating
NAM–NAG polysaccharide component of cell wall peptidoglycans.
Glu 35 and Asp 52 Are Lysozyme’s
Catalytic Residues
Lysozyme attaches to a bacterial cell wall by binding
to a hexasaccharide unit. In the process, the D-ring is distorted
toward the half-chair conformation.
•Glu 35 transfers its proton to the O1 atom
linking the D- and E-rings, the only polar
group, thereby cleaving the C1-O1 bond
(general acid catalysis).

•This step converts the D-ring to a planar

resonance-stabilized oxonium ion transition
state, whose formation is facilitated by the
strain distorting it to the half-chair
conformation

•The positively charged oxonium ion is

stabilized by the presence of the nearby
negatively charged Asp 52 carboxylate group
(electrostatic catalysis).The E-ring product is
released.
 3.The Asp 52 carboxylate group
nucleophilically attacks
the now electron-poor C1 of the D
ring to form a covalent
glycosyl–enzyme intermediate
(covalent catalysis).

4 Water replaces the E-ring product in the

active site
• Hydrolysis of the covalent bond with the
assistance of Glu 35 (general base catalysis),
which involves another oxonium ion
transition state, regenerates the active site
groups.

•The enzyme then releases the D-ring

product, completing the catalytic cycle.
Carboxypeptidase-A Mechanism
• Carboxypeptidase A is a digestive
enzyme that hydrlyzes the
carboxyterminal peptide bond in
polypeptide chain.
• Carboxypeptidase A is a single polypeptide of 307 amino
acid residues.
• There is a tightly bound zinc ion which is essential for
enzymatic activity.
• Exopeptidase, zymogen form activated by trypsin.
• Pancreatic digestive enzyme secreted to small interstine.
• Cleave from C and N termi amino acids, except proline,
lysine and arginine
Carboxy peptidase A
(1) the nucleophilic attack of the active site Ser
on the carbonyl carbon atom of the scissile peptide bond to form
the tetrahedral intermediate;

(2) the decomposition of the

tetrahedral intermediate to the acyl–enzyme intermediate through general acid catalysis
by the active site Asp-polarized His, followed by loss of the amine product and its
replacement by a water molecule;
(3) the reversal of Step 2 to form a second
tetrahedral intermediate
 Ribonuclease
• Bovine pancreatic ribonuclease A (RNase A) provides
An example of enzymatically mediated general
acid–base catalysis.
 RNase A has two essential His residues, His 12 and His 119, which act
in a concerted manner as general acid and base catalysts

1. His 12, acting as a general base, abstracts a proton from

an RNA 2I OH group, thereby promoting its nucleophilic attack on the adjacent
phosphorus atom while His 119, acting as a general acid, promotes bond scission by
protonating the leaving group.
The 2I3I-cyclic intermediate is hydrolyzed
through water replaces the leaving group.

Thus His 12 acts as a general

acid and His 119 as a general base to yield the
hydrolyzed RNA and the enzyme in its
original state.
Alcohol Dehydrogenase
• Alcohol Dehydrogenase belongs to the oxidoreductase
family of enzymes
• ADH is found in high concentrations within the human
liver and kidney
• The primary and most common role of ADH in humans
is to detoxify incoming ethanol by converting it into
acetaldehyde
• The resulting acetaldehyde, a more toxic molecule
than ethanol, is quickly converted into acetate and
other molecules easily utilized by the cell
• Incoming ethanol is converted to acetaldehyde by the mechanism below:

Ethanol + NAD+ ---------- Acetaldehyde + NADH

• Ethanol is oxidized by ADH into acetaldehyde and NADH is formed

• The highly toxic acetaldehyde is then converted to acetyl coA.
• Throughout these processes, water molecules are lost and dehydration could set in after prolonged
imbibing.
 Forms and Functions
- structure and function of ADH and associated isoenzymes

• Humans have at least nine known forms of ADH

• ADH exists as a homo or heterodimer due to the fact there are two different types
of monomer
• The two types are E and S for ethanol active and steroid active respectively.
 Characteristics of ADH
• ADH has a molecular weight of about 80 000
• There are 8 chains, 60 helices, and 74 beta strands in ADH,
It’s a dimer.
• Each subunit of one monomer contains one binding site for
NAD+ and two binding sites for Zn2+
• Each Zinc ion is ligated directly between the side chains of
Cys-46, His-67, Cys-174 and a water molecule which is
hydrogen bonded to Ser-48.
• Between the two binding sites where the zinc is located,
there are two clefts. One which binds NAD+ and one which
binds the substrate (ethanol)
• Zinc bound to Cys-46, His-67, Cys-174, and Ser-48 (Blue) and the coenzyme NAD + (purple) attached
to His-51 (yellow) and Lys-228 (cyan). The eight zinc molecules are in red. The four zincs seen easily
are not directly involved in the proton transfer chain.
COENZYMES ACTION
 COENZYMES
• Coenzymes are organic compounds required by many
enzymes for catalytic activity.

• They are often vitamins, or derivatives of vitamins.

• Sometimes they can act as catalysts in the absence of

enzymes.
 TPP
• Thiamine pyrophosphate is derived from vitamin B1

• It functions as a coenzyme vital to tissue respiration.

  
• It is required for the oxidative decarboxylation of pyruvate to
form acetyl-coenzyme A, providing entry of oxidizable
substrate into the Krebs cycle for the generation of energy. 
 TPP
• The coenzyme form of vitamin B1 is called as Thiamine
Pyrophosphate.
TPP
 NAD and NADP
• These are derived from the vitamin niacin, which is
nicotinamide adenine dinucleotide (NAD) and nicotinamide
adenine dinucleotide phosphate (NADP)
The structure and reaction of NAD+
 NAD+ is cofactor in
The alcohol dehydrogenase (ADH) reaction

NADH dissociates from the enzyme to be re-

oxidized in an independent reaction
 FAD and FMN
• Flavin nucleotides are derived from riboflavin, vitamin B2.
• These are mainly involving in oxidation and reduction
reactions.
• A molecule of riboflavin consists of a sugar alcohol, D ribitol,
attached to a chromogenic dimethyl isoalloxazine ring at
position 9.
FAD
FAD
 ROLE OF FAD AND FMN
• In vitamin B6 metabolism, the conversion of pyridoxamine phosphate to
pyridoxal phosphate is dependent upon FMN.
• L-amino oxidase uses FMN in the dehydrogenation of L-amino acid into
L-imino acid.
• In oxidative decarboxylation of pyruvate, FAD serves as an intermediate
electron carrier.
• Succinate dehydrogenase in a FAD flavoprotein that removes electrons
from succinic acid to form fumarate that forms FAD to FADH2.
 Pyridoxal phosphate (PLP)
•Pyridoxal 5-phosphate is derived from pyridoxine or pyridoxamine,
Vitamin-B6.
•It includes three compounds: pyridoxine, pyridoxal and pyridoxamine.
•This coenzyme is imporatant in amino acid metabolism, being involved in
amino transferase (transaminase), decarboxylase and racemase reactions.
•All the three forms of vitamin B6are the derivatives of pyridine, and differ
from each other in the nature of substituent at the position 4 of the ring.
•The three forms of vitamin B6 are converted to pyridoxal-5 phosphate that
acts as a coenzyme in various enzymatic reactions involoved in amino acid
metabolism.
•Pyridoxal phosphate(PALP) is the coenzyme for both glutamic
decarboxylase and GABA transaminase, each is essential for normal brain
metabolism.
VITAMIN B6
PLP
 BIOTIN
• Biotin is always found firmly bound to a side chain amino
group of lysine residues of a protein.
• Protein-bound biotin act as a carrier of CO2, which is
important in carboxylation reactions.
• Ex. Acetyl co-A carboxylase.
BIOTIN
 BIOTIN Action
• Acetyl co-A carboxylase.
• Acetyl co-A carboxylase from E.Coli to dissociate into
three distinct sub-units, one is biotincarboxyl carrier
protein (BCCP) and second one is biotin carboxylase
and third one is carboxymethyltransferase.
• The BCCP appears to act as a flexible form,
transporting the carbon dioxide from the active site of
biotin carboxylase to that of carboxyltransferase,
where it is presented to the acetyl co-A.
FOLIC ACID
 FOLIC ACID
• The reduction products of folic acid act as coenzymes.

• An enzyme folic reductase, reduces folic acid to dihydrofolic

acid(DHFA or FH2), the latter compound is further reduced by
dihydrofolic reductase to 5,6,7,8-tetrahydrofolic acid(THFA or
FH4).
FOLIC ACID
 Lipoic Acid
• In pyruvate dehydrogenase multienzyme complex also catalyses the
decarboxylation of pyruvate, but it utilizes a second coenzyme, lipoic
acid, to introduce in oxidation step and third coenzyme, Coenzyme A
(CoA.SH) to react with the acetyl-lipoamide complex, it giving acetyl-CoA
as the final product.
 Function
• Alpha-Lipoic acid has two important functions in our body.
First, it serves as a coenzyme (i.e. facilitating the action of
enzymes) in several metabolic pathways. Second, it is an
important antioxidant.
• Lipoic acid is a coenzyme for a group of enzymes (i.e.
biological catalysts) responsible for the eventual conversion of
fats, carbohydrates and proteins in to biological energy (i.e.
adenosine triphosphate or ATP). 
 Coenzyme A

• Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable

for its role in the synthesis and oxidation of fatty acids, and
the oxidation of pyruvate in the citric acid cycle.
 Function
• Since coenzyme A is, in chemical terms, a thiol, it can react
with carboxylic acids to form thioesters, thus functioning as
an acyl group carrier. It assists in transferring fatty acidsfrom
the cytoplasm to mitochondria. A molecule of coenzyme A
carrying an acetyl group is also referred to as acetyl-CoA.
When it is not attached to an acyl group, it is usually referred
to as 'CoASH' or 'HSCoA'.
Multifunctional enzyme
 PDC Multienzyme complex
The conversion of pyruvate to acetyl-CoA, catalyzed by
highly organized multienzyme pyruvate dehydrogenase
Complex by oxidative decarboxylation

Overall reaction
Pyruvate dehydrogenase complex is an assembly of
three individual enzymes:

Pyruvate dehydrogenase (E1),

Dihydrolipoyl transacetylase (E2) and
Dihydrolipoyl dehydrogenase (E3).
E1 first catalyzes the decarboxylation of pyruvate,
producing hydroxyethyl-TPP, and then the oxidation
of the hydroxyethyl group to an acetyl group.
In E2 the hydroxyethyl oxidation reduce the
disulfide of lipoate bound to E2, and the acetyl
group is transferred into thioester linkage with on -
SH group of reduced lipoate.
E2 catalyzes the transfer of the acetyl group to
coenzyme A, forming acetyl-CoA.
E3 catalyzes the regeneration of the disulfide
(oxidized) form of lipoate; electrons pass first to
FAD and then to NAD+.
Mechanism
PDC allostric Regulation
Ribozyme
The first ribozyme was discovered in the 1980s by Thomas
R. Cech, during studies of RNA splicing in the ciliated
protozoan Tetrahymena thermophile.
Sidney Altman, who was working on ribonucleoprotein,
RNaseP.
In 1989, Thomas R.Cech and Sydney Altman won the Nobel
prize in chemistry for their discovery of catalytic properties
of RNA.
ribozymes were found in the intron of an RNA transcript
and RNA component of RNaseP, which is involved in
processing of pre-tRNAs.
Ribozymes often require divalent metal ions such as Mg2+
as cofactors.
Many natural ribozymes catalyze either their own cleavage
or the cleavage of other RNAs, but they have also been
found to catalyze the aminotransferase activity of the
ribosome.
RNase P, Group I and Group II introns, hairpin ribozyme,
hammerhead ribozyme, hepatitis delta virus ribozyme,
and tetrahymena ribozyme.
Isoenzymes
Multiple forms of an enzyme that catalyzes the same
reaction but differ from each other in their amino acid
sequence composition, substrate affinity, Vmax, and /or
regulatory properties are described as isozymes.

Ex; lactate dehydrogenase (LDH)

HHHH (H4) LDH1 In the heart and RBCs
HHHM(H3M) LDH2 In the reticuloendothelial system
HHMM (H2M2) LDH3 In the lungs
HMMM (HM3) LDH4 In the kidneys, placenta
MMMM (M4) LDH5 In the liver and striated muscle
 Feed back regulation

Feedback Inhibition in Metabolic Pathways

• Cells also use feedback inhibition to regulate enzyme activity in

metabolism. Cells have evolved to use the products of their own reactions
for feedback inhibition of enzyme activity.

• Feedback inhibition involves the use of a reaction product to regulate its

own further production.

• Metabolic reactions, such as anabolic and catabolic processes, must

proceed according to the demands of the cell. In order to maintain
chemical equilibrium and meet the needs of the cell, some metabolic
products inhibit the enzymes in the chemical pathway.
 Carbohydrate metabolism

The activity of PFK-1 is inhibited by high concentration of ATP and this inhibition is
overcome by AMP, Pi and fructose-6-phosphate
Metabolic pathway a substrate, S, is transformed into a product, P, through a
series of enzymatic reactions and if P accumulates in amounts that are not
immediately needed by the cell then this product specifically inhibits the action
of the first enzyme, E1, of the pathway. Thus, further transformation of S in
that direction is stopped. This is called feedback inhibition or end-product
inhibition.
 Nucleic acid metabolism
• The following are the well established examples showing feedback
inhibition: 1. Inhibition of enzyme aspartate transcarbamoylase (ATCase)
by nucleotide cytidine triphosphate (CTP). ATCase catalyzes the synthesis
of nucleoside triphosphate, CTP, from aspartic acid and carbamoyl
phosphate through a sequence of reactions. The end product of the
pathway, CTP, is responsible for inhibition of first enzyme when needed,
as shown below:
Inhibition of enzyme L-threonine deaminase by
amino acid isoleucine
Thank you