Download Allosteric enzymes

ENZYME ACTVIATORS:2- ISOENZYMES:
Some of the enzymes are present in more than one form called
isoenzymes, e.g. Trypsinogen isoenzymes are present in three
conformational structures :1- cationic Trypsinogen
2- anionic Trypsinogen
3- mesotrypsinogen
storage and packing in acidic media to inhibit enzyme activity
synthesis and storage as inactive precursor forms.
some of the enzymes that are stored in the pancreas before
secretion as inactive precursor forms, then activated when they
enter the duodenum
Activation of these enzymes takes place in the microvilli where
Enterokinase, activates Trypsinogen by removing (by hydrolysis)
an N-terminal hexa peptide fragment of the molecule (Val–Asp–
Asp–Asp–Asp–Lys). The active form, Trypsin, then catalyzes the
activation of the other inactive proenzymes.
Of note, many key digestive enzymes, such as α-amylase and
lipase, are present in the pancreas in their active forms.
Presumably, these enzymes would not cause pancreatic cellular
damage if released into the pancreatic cell/tissue because there
is no starch, glycogen or triglyceride substrate for these enzymes
in pancreatic tissue.
3- Coenzyme:
Coenzymes are organic cofactors. They are Coenzymes serve as a
second substrates for enzymatic reactions, such as nucleotide
phosphates and vitamins. When bound tightly to the enzyme,
coenzymes are called prosthetic groups
3- Coenzyme:
For example, NAD⁺ as a cofactor may be reduced to nicotinamide
adenine dinucleotide phosphate (NADH) in a reaction in which
the primary substrate is oxidized (the equation below). Increasing
coenzyme concentration will increase the velocity of an enzymatic
reaction.
4- Holoenzyme:
When bound tightly to the enzyme, the coenzyme is called a prosthetic group. The enzyme portion
(apoenzyme), with its respective coenzyme, forms a complete and active system, a holoenzyme.
Cofactors are generally stable to heat while some enzymes Lose activity on heat .
When the cofactor is removed, the remaining protein which is catalytic in active by itself,
5- Zymogen:
Some enzymes, mostly digestive enzymes, are originally secreted
from the organ of production in a structurally inactive form, called
a proenzyme or zymogen. Other enzymes later alter the structure
of the zymogen to make active sites available by hydrolyzing
specific amino acid residues. This mechanism prevents digestive
enzymes from digesting their place of synthesis. Trypsinogen, is a
precursor of trypsin
This figure indicate the activation of Inactive Trypsinogen into Trypsin in small
intestine by Enterokinase.
TABLE of some enzymes which indicate the effect of coenzyme on an enzyme activity.
Enzymes
Vitamin
GOT
B6
GPT
B6
(GOT, GPT)
Effect on enzyme activity
Active Enzyme
Active Enzyme
Loss of enzyme activity.
No vitamin B6
*Some enzymes not need Co-factors like Urease.
16
Types Of Enzymes:
┌▬▬▬▬▬ Enzymes▬▬▬▬┐
Ordinary Enzymes
Regulatory or Allosteric Enzyme
1- Obeys Michalis-Menton equation. 1-Not obeys Michalis-Menton equation.
2- Composed of one unit.
2- Composed of more than one unit.
3-The reaction is reversible
3- The reaction one direction
4-The reaction curve of enzyme
with substrate is hyperbolic.
4- The reaction curve of enzyme
with substrate is sigmoid (S- shape).
5-Not shows allosteric property
6- Ordinary Enzyme
5-Shows allosteric property.
6- Allosteric Enzyme
16
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Regulation of Enzyme Activity :a- Allosteric enzymes:-
In allosteric regulation, the activity of an enzyme is regulated by
reversible binding (non-covelent) of an effectors molecule to a site
on the enzyme other than the active site, known as the allosteric
enzyme. Allosteric effectors can be either positive or negative.
Negative effectors decrease the reaction rate, whereas positive
effectors increase it the reaction rate, as shown:
Positive effector
No effector
V
Negative effector
[S]
b - Feedback inhibition:Feedback inhibition usually regulates pathways of enzyme
involved in the syntheses of biological molecules any metabolic
pathways are controlled by the mechanism of feedback inhibition,
in which the end product of the pathway allosterically inhibits the
first committed enzyme of the pathway, the first enzyme whose
product cannot branch into any other pathway in the cell :E1
A
B
Feedback Inhibition
C
P
Renin-Angiotensin system (RAS)
If an individuals blood pressure drops as in case of
hemorrhaging the kidneys secret the enzyme Renin (some times
considered as a hormone) into the blood stream.
High Blood Pressure disease:
Angiotensinogen + Renin enzyme → Angiotensin I
Angiotensin I + ACE enzyme → Angiotensin II
[ACE= Angiotensin converting enzyme] ,the Inhibitor of ACE
enzyme is Captopril drug.
The function of Angiotensin-converting enzyme:
1-Angiotensin-converting enzyme, ACE is a zinc metalloenzyme.
The zinc ion Zn⁺² is essential to its activity (hydrolysis), so a
pharmaceutical drug (Captopril) for treatment of cardiovascular
diseases.
2-ACE is a central component in the plasma which requires
chloride ion for its activation, and in controlling blood pressure
so ACE indirectly increases blood pressure by causing blood
vessels to constrict.
c- Enzyme Cascades
Enzyme cascades consist of a series of enzymes that sequentially
activate each other, usually by covalent modification. Enzyme
cascades amplify a weak regulatory signal so that it has a strong
effect on a biochemical reaction. The first enzyme in the cascade is
activated by the initial regulatory signal
c- Enzyme Cascades
Example (Drugs as hormone initiator) Hormones which secreted in
the blood stream where they travel through and effect on the target
cells), and Blood clotting is mediated by a cascade of proteolytic
activation that assure a rapid and amplified response to trauma. the
last enzyme in the cascade controls is the regulated process.
Hormone
1 Enzyme 1
1 Enzyme 1
(inactive)
(active)
100 Enzyme
2
100 Enzyme
2
(inactive)
(active)
10,00 Enzyme 3
10,00 Enzyme 3
(inactive)
(active)
106 A
Figure-2 :- A hypothetical enzyme cascade.
106 B
prothrombin activator complex
Prothrombin
(inactive)
Thrombin (active)
Fibrinogen (inactive)
Fibrin
Fibrin (active)
Fibrin
Fibrin
Fibrin
When Fibrinogen has been converted to Fibrin, the clot that
forms is a polymerized Fibrin threads that become attached to
blood cells, blood vessels walls, and plasma proteins . Fibrin
threads is unstable so the enzyme Transglutaminase stabilized the
Fibrin clot by forming covalent cross-linkages between Fibrin
threads in the clot. Certain natural proteins and Vitamin K as well
as synthetic antagonists are effective in controlling this bleeding
.The following figure(2) below indicate that
Figure (2): Blood Clotting formation
c- An example for Enzyme Cascades is:
Blood Clotting
Bleeding problems may have origin in naturally occurring.
Blood clotting is mediated by a cascade of proteolytic activation
that assure a rapid and amplified response to trauma. So blood
clotting is activated by chemicals (such as enzymes) secreted by the
cell at the damaged site by involving series of proteolytic reactions
that result in formation of prothrombin activator complex by
converting Prothrombin into Thrombin . Thrombin cleaves four
peptid bonds in Fibrinogen to produce Fibrin.