1. 1- cationic Trypsinogen 2- anionic Trypsinogen 3- mesotrypsinogen
محاضرة الانزيمات 1 4
ENZYME ACTVIATORS:-
1- COFACTORS
2- ISOENZYMES:
Some of the enzymes are present in more than one form having the same molecular weight and differ in conformational structures called isoenzymes, e.g. Trypsinogen isoenzymes are present in three conformational structures :-
1- cationic Trypsinogen
2- anionic Trypsinogen
3- mesotrypsinogen
These conformational structures of isoenzymes are capable of digesting the cell and causing significant damage. But there are mechanisms to prevent these enzymes from potentially digesting the pancreas including:
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 surface of the duodenal lumen, microvilli where Enterokinase, activates Trypsinogen by removing (by hydrolysis) an N-terminal hexapeptide 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.

2. 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. 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.
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, its a storage of an inactive form of trypsin so that it may be kept in the pancreas and released in significant amount when required for protein digestion. Trypsin is formed in the small intestine when its proenzyme Enterokinase produced by pancreas.
This figure indicate the activation of
Inactive Trypsinogen into Trypsin
in small intestine by Enterokinase..

3. Types Of Enzymes: ▬▬▬▬▬ Enzymes▬▬▬▬┐┌
TABLE of some enzymes which indicate the effect of coenzyme on an enzyme activity.
Effect on enzyme activity
Vitamin
Enzymes
Active Enzyme B6
GOT
GPT
Loss of enzyme activity.
No vitamin B6
(GOT, GPT)
*Some enzymes not need Co-factors like Urease.
Types Of Enzymes:
Ordinary Enzymes Regulatory or Allosteric Enzymes
1- Obeys Michalis-Menton equation. 1-Not obeys Michalis-Menton equation
2- Composed of one unit Composed of more than one unit.
3-The reaction is reversible The reaction one direction
4-The reaction curve of enzyme The reaction curve of enzyme
with substrate is hyperbolic with substrate is sigmoid (S- shape).
5-Not shows allosteric property Shows allosteric property.
6- Ordinary Enzyme Allosteric Enzyme
▬▬▬▬▬ Enzymes▬▬▬▬┐┌ 16

4. P A B C E1 Feedback Inhibition 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:
[S] V
Positive effector
No effector
Negative effector
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 committed enzyme is the first enzyme whose product cannot branch into any other pathway in the cell but must proceed to from the end product of that pathway:- A B C P E1
Feedback Inhibition

5. 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]
Inhibitor of ACE enzyme is Captopril drug so that enzyme is inhibited by Captopril to give the product Angiotensin II.
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). Therefore, ACE can be inhibited by 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, it regulates the volume of fluids in the body. ACE converts the hormone angiotensin I to the active vasoconstrictor angiotensin II, so ACE indirectly increases blood pressure by causing blood vessels to constrict. For this reason, drugs known as ACE inhibitors (Captopril) are used to lower blood pressure Fig(1).
Fig(1): Feedback inhibition

6. 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 ,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
(inactive)
(active)
100 Enzyme 2
10,00 Enzyme 3
106 B
106 A
Figure-2 : A hypothetical enzyme cascade.

7. c- Enzyme Cascades an example for this 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.
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
prothrombin activator complex
Thrombin (active)
Prothrombin
(inactive)
Fibrinogen (inactive)
Fibrin (active)
Fibrin
Figure (2): Blood Clotting formation