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Chapter 6
Local controls
Course Coordinator: Dr. Ziad H. Al-Oanzi
Enzymes
Enzymes
Enzyme Action
Factors Affecting Enzyme Action
The effect of enzyme inhibition
Enzymes
• Catalysts for biological
reactions
• Most are proteins
• Lower the activation energy
• Increase the rate of reaction
• Activity lost if denatured
• May be simple proteins
• May contain cofactors such
as metal ions or organic
(vitamins)
‫محفزات‬
‫التفاعالت‬
‫البيولوجية‬
•
‫معظمها‬
‫بروتينات‬
•
‫خفض‬
‫التنشيط‬ ‫طاقة‬
•
‫التفاعل‬ ‫زيادةمعدل‬
•
‫تم‬
‫فقدان‬
‫حالة‬ ‫في‬ ‫النشاط‬
‫التشويه‬
•
‫بسي‬ ‫بروتينات‬ ‫قدتكون‬
‫طة‬
•
‫مساعدة‬ ‫عوامل‬ ‫على‬ ‫قدتحتوي‬
‫العض‬ ‫أو‬ ‫المعدنية‬ ‫األيونات‬ ‫مثل‬
‫وية‬
(
‫الفيتامينات‬
)
Enzymes
• A protein catalyst
• Enzymes are important
proteins found in living
things. An enzyme is a
protein that changes the
rate of a chemical
reaction.
• They speed metabolic
reactions.
‫محفزالبروتين‬
•
‫اإلنزيمات‬
‫هي‬
‫بروتينات‬
‫مهمة‬
‫موجودة‬
‫في‬
‫الكائنات‬
‫الحية‬
.
‫ان‬
‫إنزيم‬
‫هو‬
‫البروتين‬
‫الذي‬
‫معدل‬ ‫يغير‬
‫المادةالكيميائية‬
‫ردفعل‬
.
•
‫أنها‬
‫التفاعالت‬ ‫تسرع‬
‫األيضية‬
.
Examples
 digestion
 synthesis
+
+
Enzymes are proteins
• Each enzyme is the specific helper to
a specific reaction
– each enzyme needs to be the right shape for the
job
– enzymes are named for the reaction
they help
• sucrase breaks down sucrose
• proteases breakdown proteins
• lipases breakdown lipids
• DNA polymerase builds DNA
7
1. Oxidoreductases: transfer of electron (inform of
hydride ions or H atoms)
2. Transferases: transfer functional groups between
donor and acceptor molecules.
3. Hydrolases:Add water across a bond,
hydrolyzing it.
4. Lyases: cleavage of C-C, C-O, C-N, or other
bonds by elimination, leaving double bonds or
rings or addition of groups to double bonds.
5. Isomerases: transfer of groups within molecules
to yield isomeric forms
6. Ligases: formation of C-C, C-S, C_O and C-N
bonds by condensation reactions coupled to
cleavage ofA
TP or similar cofactor
Enzyme Classification
Enzymes aren’t used up
• Enzymes are not changed by the reaction
– used only temporarily
– re-used again for the same reaction with other
molecules
– very little enzyme needed to help in many
reactions
enzyme
substrate product
active site
It’s shape that matters!
• Lock & Key model
– shape of protein
allows enzyme &
substrate to fit
– specific enzyme for
each specific
reaction
‫لوك‬
&
‫ذ‬ ‫نموذج‬ ‫كه‬
-
‫شكل‬
‫البروتين‬
‫يسمح‬
‫لإلنزيم‬
&
‫الركيزةلتناسب‬
-
‫إنزيم‬
‫محدد‬
‫لكل‬
‫محدد‬
‫رد‬
‫فعل‬
Enzyme vocabulary
• Enzyme
– helper protein molecule
• Substrate
– molecule that enzymes work on
• Products
– what the enzyme helps produce from the
reaction
• Active site
– part of enzyme
that substrate
molecule fits into
‫إنزيم‬
-
‫المساعد‬ ‫جزيءالبروتين‬
•
‫المادة‬
‫المتفاعلة‬
-
‫اإلنزيمات‬ ‫عليه‬ ‫تعمل‬ ‫الجزيءالذي‬
•
‫منتجات‬
-
‫التفاعل‬ ‫من‬ ‫إنتاجه‬ ‫على‬ ‫اإلنزيم‬ ‫مايساعد‬
•
‫موقع‬
‫نشط‬
-
‫اإلنزيم‬ ‫جزءمن‬
‫الذي‬
‫الركيزة‬
‫يناسبالجزيء‬
Factors affecting Enzymes
• substrate concentration
• pH
• temperature
• inhibitors.
‫تركيزالركيزة‬
•
‫الرقم‬
‫الهيدروجيني‬
•
‫درجة‬
‫حرارة‬
•
‫مثبطات‬
.
Substrate concentration:
Non-enzymic reactions
The increase in velocity is proportional to
the substrate concentration.
Substrate concentration:
Enzymic reactions
• Faster reaction but it reaches a
saturation point when all the
enzyme molecules are occupied
• Alter the concentration of the
enzyme then Vmax will change too.
The effect of pH
Optimum pH values
Enzyme
activity
Trypsin
Pepsin
7
pH
1 3 5 9 11
The effect of temperature
Temperature / °C
Enzyme
activity
0 10 20 30 40 50
Increasing
number of
collisions (Q10)
Denaturation
Optimum
• Inhibitors are chemicals that reduce the rate of enzymic
reactions.
• The are usually specific and they work at low
concentrations.
• They block the enzyme but they do not usually destroy it.
• Many drugs and poisons are inhibitors of enzymes
in the nervous system.
‫عىل‬ ‫تعمل‬ ‫كيميائية‬‫مواد‬ ‫ي‬
‫ه‬ ‫المثبطات‬
‫تقليل‬
‫معدل‬
‫التفاعالت‬
‫األنزيمية‬
.
•
‫منخفضة‬ ‫ات‬‫ز‬
‫كت‬ ‫ر‬
‫بت‬ ‫وتعمل‬ ‫محددة‬ ‫تكون‬ ‫ما‬ ‫عادة‬
.
•
‫عادة‬ ‫تدمره‬ ‫ال‬ ‫ولكنها‬ ‫اإلنزيم‬ ‫تمنع‬ ‫إنها‬
.
•
‫عىل‬ ‫والسموم‬ ‫األدوية‬ ‫من‬ ‫العديد‬ ‫تعمل‬
‫تثبيط‬
‫اإلنزيمات‬
‫ي‬
‫ز‬
‫ف‬
‫الجهاز‬
‫ي‬
‫العصب‬
Enzyme Inhibition
16
The effect of enzyme inhibition
• Irreversible inhibitors: Combine with the
functional groups of the amino acids in the
active site, irreversibly.
Examples: nerve gases and pesticides,
containing organophosphorus, combine with
serine residues in the enzyme acetylcholine
esterase.
‫مثبطات‬
‫ال‬
‫فيها‬ ‫رجعة‬
:
‫مع‬ ‫يتحد‬
‫المجموعات‬
‫الوظيفية‬
‫لألحماض‬
‫الموقع‬ ‫في‬ ‫األمينية‬
‫النشط‬
‫بشكل‬
‫ال‬
‫فيه‬ ‫رجعة‬
.
‫أمثلة‬
:
‫والمبيدات‬ ‫األعصاب‬ ‫غازات‬
‫الحشرية‬
‫تحتوي‬
‫على‬
‫مع‬ ‫وتتحد‬ ،‫العضوي‬ ‫الفوسفور‬
‫بقايا‬
‫السيرينفي‬
‫إنزيم‬
‫كولين‬ ‫أستيل‬
.
16
17
The effect of enzyme inhibition
• Reversible inhibitors: These can be washed
out of the solution of enzyme by dialysis.
There are two categories.
‫مثبطات‬
‫عكسية‬
:
‫يمكن‬
‫محلول‬ ‫من‬ ‫غسلها‬
‫اإلنزيم‬
‫عن‬
‫طريق‬
‫الكلى‬ ‫غسيل‬
.
‫هناكفئتان‬
.
17
18
Competitive Inhibition
A competitive inhibitor
• Has a structure similar to
substrate
• Occupies active site
• Competes with substrate
for
active site
• Has effect reversed by
increasing substrate
concentration
‫مثبط‬
‫تنافسي‬
•
‫لديه‬
‫هيكل‬
‫للركيزة‬ ‫مماثل‬
•
‫يحتل‬
‫موقعا‬
‫نشطا‬
•
‫يتنافس‬
‫مع‬
‫للموقع‬ ‫الركيزة‬
‫النشط‬
•
‫طريق‬ ‫عن‬ ‫عكسي‬ ‫لهتأثير‬
‫زيادة‬
‫تركيزالركيزة‬
18
19
Succin
ate
Fumarate + 2H++ 2e-
Succinate
dehydrogenase
CHCOOH
CHCOOH
COOH
CH2COOH
CH2
CH2COOH
COOH
Malonate
The effect of enzyme inhibition
20
Statin drugs as examples of competitive inhibitors
• This group of anti- hypercholesterolemic agents
competitively inhibits the first committed step in
cholesterol synthesis.
• This reaction is catalyzed by HMG–CoA reductase.
• Statin drugs, are structural analogs of the natural
substrate for this enzyme, and compete effectively to
inhibit HMG-CoAreductase.
• By doing so, they inhibit de novo cholesterol
synthesis, thereby lowering plasma cholesterol levels
•
‫لفرط‬ ‫المضادة‬ ‫العوامل‬ ‫من‬ ‫هذهالمجموعة‬
‫الكولسترول‬
‫تمنعبشكل‬
‫تنافسي‬
‫في‬ ‫األولى‬ ‫الخطوة‬
‫تخليق‬
‫الكوليسترول‬
.
‫المختزل‬
.
HMG-CoA •
‫بواسطة‬ ‫التفاعل‬ ‫هذا‬ ‫يتمتحفيز‬
‫إنزيم‬
•
‫لهذا‬ ‫الطبيعية‬ ‫للركيزة‬ ‫هيكلية‬ ‫نظيرات‬ ‫هي‬ ‫أدويةالستاتين‬
HMG-CoA
‫لتثبيط‬ ‫فعال‬ ‫بشكل‬ ‫وتتنافس‬،‫اإلنزيم‬
‫إنزيم‬
‫المختزل‬
.
•
،‫نوفو‬ ‫دي‬ ‫الكولسترول‬ ‫تخليق‬ ‫تمنع‬ ‫فإنها‬ ،‫بذلك‬ ‫القيام‬ ‫منخالل‬
‫في‬ ‫الكولسترول‬ ‫مستويات‬ ‫وبالتاليخفض‬
‫البالزما‬
21
Other examples of competitive inhibitors as drugs
 β-lactam antibiotics, such as penicillin and amoxicillin, act by inhibiting
enzymes involved in bacterial cell wall synthesis.
 Angiotensin-converting enzyme (ACE) inhibitors. They lower blood
pressure by blocking the enzyme that cleaves angiotensin I to form the
potent vasoconstrictor, angiotensin II. These drugs, which include cause
vasodilation and a resultant reduction in blood pressure.
 Allopurinol, a drug used to treat gout, decreases urate production by
inhibiting xanthine oxidase.
-
‫ب‬
-
‫تثبيط‬ ‫طريق‬ ‫عن‬ ،‫واألموكسيسيلين‬ ‫البنسلين‬ ‫مثل‬ ،‫الالكتامية‬ ‫الحيوية‬ ‫المضادات‬ ‫تعمل‬
‫اإلنزيمات‬
‫جدار‬ ‫تكوين‬ ‫في‬ ‫المشاركة‬
‫البكتيرية‬ ‫الخلية‬
.
‫طريق‬ ‫عن‬ ‫الدم‬ ‫ضغط‬ ‫تخفض‬ ‫إنها‬
.
(
ACE) –
‫مثبطات‬
‫اإلنزيم‬
‫المحول‬
‫لألنجيوتنسين‬
‫منعاإلنزيم‬
‫يقسم‬ ‫الذي‬
‫األنجيوتنسين‬
1
،‫القوي‬ ‫األوعية‬ ‫مضيق‬ ‫ليشكل‬
‫أنجيوتنسين‬
2
.
‫وما‬ ‫الدموية‬ ‫األوعية‬ ‫توسع‬ ‫تسبب‬ ‫تشمل‬ ‫والتي‬ ،‫األدوية‬ ‫هذه‬
‫ينتج‬
‫عنها‬
‫من‬
‫الدم‬ ‫ضغط‬ ‫في‬ ‫انخفاض‬
.
-
‫طريق‬ ‫عن‬ ‫اليورات‬ ‫إنتاج‬ ‫من‬ ‫يقلل‬ ،‫النقرس‬ ‫لعالج‬ ‫يستخدم‬ ‫دواء‬ ‫وهو‬،‫الوبيورينول‬
‫الزانثين‬ ‫تثبيطأوكسيديز‬
.
21
22
Noncompetitive Inhibition
A noncompetitive inhibitor
• Does not have a structure like substrate
• Binds to the enzyme but not active site
• Changes the shape of enzyme and active site
• Substrate cannot fit altered active site
• No reaction occurs
• Effect is not reversed by adding substrate
‫مثبط‬
‫غير‬
‫تنافسي‬
•
‫ليس‬
‫لديها‬
‫الركيزة‬ ‫مثل‬ ‫هيكل‬
•
‫يرتبطب‬
‫اإلنزيم‬
ً‫ا‬‫نشط‬ ً‫ا‬‫موقع‬ ‫ليس‬ ‫ولكنه‬
•
‫النشط‬ ‫والموقع‬ ‫اإلنزيم‬ ‫يغيرشكل‬
•
‫تغييره‬ ‫تم‬ ‫الذي‬ ‫النشط‬ ‫الموقع‬ ‫تناسب‬ ‫أن‬ ‫للركيزة‬ ‫اليمكن‬
•
‫فعل‬ ‫رد‬ ‫أي‬ ‫اليحدث‬
•
‫بإضافة‬ ‫التأثير‬ ‫عكس‬ ‫اليتم‬
‫الركيزة‬
23
Examples of noncompetitive inhibitors:
• Lead poisoning
lead forms covalent bonds with the sulfhydryl side chains of cysteine in
proteins. The binding of the heavy metal shows noncompetitive inhibition
(covalent bonding).
– Ferrochelatase, an enzyme that catalyzes the insertion of Fe2+ into protoporphyrin, is an
example of an enzyme sensitive to inhibition by lead.
• Other examples of noncompetitive inhibition are certain insecticides,
whose neurotoxic effects are a result of their irreversible binding at the
catalytic site of the enzyme acetylcholinesterase (an enzyme that cleaves
the neurotransmitter, acetylcholine).
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Chaptl;k;lkl;k;lkk;lk;lk;lk;lk;lkl;ker 6.pptx

  • 1. Chapter 6 Local controls Course Coordinator: Dr. Ziad H. Al-Oanzi
  • 2. Enzymes Enzymes Enzyme Action Factors Affecting Enzyme Action The effect of enzyme inhibition
  • 3. Enzymes • Catalysts for biological reactions • Most are proteins • Lower the activation energy • Increase the rate of reaction • Activity lost if denatured • May be simple proteins • May contain cofactors such as metal ions or organic (vitamins) ‫محفزات‬ ‫التفاعالت‬ ‫البيولوجية‬ • ‫معظمها‬ ‫بروتينات‬ • ‫خفض‬ ‫التنشيط‬ ‫طاقة‬ • ‫التفاعل‬ ‫زيادةمعدل‬ • ‫تم‬ ‫فقدان‬ ‫حالة‬ ‫في‬ ‫النشاط‬ ‫التشويه‬ • ‫بسي‬ ‫بروتينات‬ ‫قدتكون‬ ‫طة‬ • ‫مساعدة‬ ‫عوامل‬ ‫على‬ ‫قدتحتوي‬ ‫العض‬ ‫أو‬ ‫المعدنية‬ ‫األيونات‬ ‫مثل‬ ‫وية‬ ( ‫الفيتامينات‬ )
  • 4. Enzymes • A protein catalyst • Enzymes are important proteins found in living things. An enzyme is a protein that changes the rate of a chemical reaction. • They speed metabolic reactions. ‫محفزالبروتين‬ • ‫اإلنزيمات‬ ‫هي‬ ‫بروتينات‬ ‫مهمة‬ ‫موجودة‬ ‫في‬ ‫الكائنات‬ ‫الحية‬ . ‫ان‬ ‫إنزيم‬ ‫هو‬ ‫البروتين‬ ‫الذي‬ ‫معدل‬ ‫يغير‬ ‫المادةالكيميائية‬ ‫ردفعل‬ . • ‫أنها‬ ‫التفاعالت‬ ‫تسرع‬ ‫األيضية‬ .
  • 6. Enzymes are proteins • Each enzyme is the specific helper to a specific reaction – each enzyme needs to be the right shape for the job – enzymes are named for the reaction they help • sucrase breaks down sucrose • proteases breakdown proteins • lipases breakdown lipids • DNA polymerase builds DNA
  • 7.
  • 8. 7 1. Oxidoreductases: transfer of electron (inform of hydride ions or H atoms) 2. Transferases: transfer functional groups between donor and acceptor molecules. 3. Hydrolases:Add water across a bond, hydrolyzing it. 4. Lyases: cleavage of C-C, C-O, C-N, or other bonds by elimination, leaving double bonds or rings or addition of groups to double bonds. 5. Isomerases: transfer of groups within molecules to yield isomeric forms 6. Ligases: formation of C-C, C-S, C_O and C-N bonds by condensation reactions coupled to cleavage ofA TP or similar cofactor Enzyme Classification
  • 9.
  • 10. Enzymes aren’t used up • Enzymes are not changed by the reaction – used only temporarily – re-used again for the same reaction with other molecules – very little enzyme needed to help in many reactions enzyme substrate product active site
  • 11.
  • 12. It’s shape that matters! • Lock & Key model – shape of protein allows enzyme & substrate to fit – specific enzyme for each specific reaction ‫لوك‬ & ‫ذ‬ ‫نموذج‬ ‫كه‬ - ‫شكل‬ ‫البروتين‬ ‫يسمح‬ ‫لإلنزيم‬ & ‫الركيزةلتناسب‬ - ‫إنزيم‬ ‫محدد‬ ‫لكل‬ ‫محدد‬ ‫رد‬ ‫فعل‬
  • 13. Enzyme vocabulary • Enzyme – helper protein molecule • Substrate – molecule that enzymes work on • Products – what the enzyme helps produce from the reaction • Active site – part of enzyme that substrate molecule fits into ‫إنزيم‬ - ‫المساعد‬ ‫جزيءالبروتين‬ • ‫المادة‬ ‫المتفاعلة‬ - ‫اإلنزيمات‬ ‫عليه‬ ‫تعمل‬ ‫الجزيءالذي‬ • ‫منتجات‬ - ‫التفاعل‬ ‫من‬ ‫إنتاجه‬ ‫على‬ ‫اإلنزيم‬ ‫مايساعد‬ • ‫موقع‬ ‫نشط‬ - ‫اإلنزيم‬ ‫جزءمن‬ ‫الذي‬ ‫الركيزة‬ ‫يناسبالجزيء‬
  • 14. Factors affecting Enzymes • substrate concentration • pH • temperature • inhibitors. ‫تركيزالركيزة‬ • ‫الرقم‬ ‫الهيدروجيني‬ • ‫درجة‬ ‫حرارة‬ • ‫مثبطات‬ .
  • 15. Substrate concentration: Non-enzymic reactions The increase in velocity is proportional to the substrate concentration. Substrate concentration: Enzymic reactions • Faster reaction but it reaches a saturation point when all the enzyme molecules are occupied • Alter the concentration of the enzyme then Vmax will change too.
  • 16. The effect of pH Optimum pH values Enzyme activity Trypsin Pepsin 7 pH 1 3 5 9 11
  • 17. The effect of temperature Temperature / °C Enzyme activity 0 10 20 30 40 50 Increasing number of collisions (Q10) Denaturation Optimum
  • 18. • Inhibitors are chemicals that reduce the rate of enzymic reactions. • The are usually specific and they work at low concentrations. • They block the enzyme but they do not usually destroy it. • Many drugs and poisons are inhibitors of enzymes in the nervous system. ‫عىل‬ ‫تعمل‬ ‫كيميائية‬‫مواد‬ ‫ي‬ ‫ه‬ ‫المثبطات‬ ‫تقليل‬ ‫معدل‬ ‫التفاعالت‬ ‫األنزيمية‬ . • ‫منخفضة‬ ‫ات‬‫ز‬ ‫كت‬ ‫ر‬ ‫بت‬ ‫وتعمل‬ ‫محددة‬ ‫تكون‬ ‫ما‬ ‫عادة‬ . • ‫عادة‬ ‫تدمره‬ ‫ال‬ ‫ولكنها‬ ‫اإلنزيم‬ ‫تمنع‬ ‫إنها‬ . • ‫عىل‬ ‫والسموم‬ ‫األدوية‬ ‫من‬ ‫العديد‬ ‫تعمل‬ ‫تثبيط‬ ‫اإلنزيمات‬ ‫ي‬ ‫ز‬ ‫ف‬ ‫الجهاز‬ ‫ي‬ ‫العصب‬ Enzyme Inhibition
  • 19. 16 The effect of enzyme inhibition • Irreversible inhibitors: Combine with the functional groups of the amino acids in the active site, irreversibly. Examples: nerve gases and pesticides, containing organophosphorus, combine with serine residues in the enzyme acetylcholine esterase. ‫مثبطات‬ ‫ال‬ ‫فيها‬ ‫رجعة‬ : ‫مع‬ ‫يتحد‬ ‫المجموعات‬ ‫الوظيفية‬ ‫لألحماض‬ ‫الموقع‬ ‫في‬ ‫األمينية‬ ‫النشط‬ ‫بشكل‬ ‫ال‬ ‫فيه‬ ‫رجعة‬ . ‫أمثلة‬ : ‫والمبيدات‬ ‫األعصاب‬ ‫غازات‬ ‫الحشرية‬ ‫تحتوي‬ ‫على‬ ‫مع‬ ‫وتتحد‬ ،‫العضوي‬ ‫الفوسفور‬ ‫بقايا‬ ‫السيرينفي‬ ‫إنزيم‬ ‫كولين‬ ‫أستيل‬ . 16
  • 20. 17 The effect of enzyme inhibition • Reversible inhibitors: These can be washed out of the solution of enzyme by dialysis. There are two categories. ‫مثبطات‬ ‫عكسية‬ : ‫يمكن‬ ‫محلول‬ ‫من‬ ‫غسلها‬ ‫اإلنزيم‬ ‫عن‬ ‫طريق‬ ‫الكلى‬ ‫غسيل‬ . ‫هناكفئتان‬ . 17
  • 21. 18 Competitive Inhibition A competitive inhibitor • Has a structure similar to substrate • Occupies active site • Competes with substrate for active site • Has effect reversed by increasing substrate concentration ‫مثبط‬ ‫تنافسي‬ • ‫لديه‬ ‫هيكل‬ ‫للركيزة‬ ‫مماثل‬ • ‫يحتل‬ ‫موقعا‬ ‫نشطا‬ • ‫يتنافس‬ ‫مع‬ ‫للموقع‬ ‫الركيزة‬ ‫النشط‬ • ‫طريق‬ ‫عن‬ ‫عكسي‬ ‫لهتأثير‬ ‫زيادة‬ ‫تركيزالركيزة‬ 18
  • 22. 19 Succin ate Fumarate + 2H++ 2e- Succinate dehydrogenase CHCOOH CHCOOH COOH CH2COOH CH2 CH2COOH COOH Malonate The effect of enzyme inhibition
  • 23. 20 Statin drugs as examples of competitive inhibitors • This group of anti- hypercholesterolemic agents competitively inhibits the first committed step in cholesterol synthesis. • This reaction is catalyzed by HMG–CoA reductase. • Statin drugs, are structural analogs of the natural substrate for this enzyme, and compete effectively to inhibit HMG-CoAreductase. • By doing so, they inhibit de novo cholesterol synthesis, thereby lowering plasma cholesterol levels • ‫لفرط‬ ‫المضادة‬ ‫العوامل‬ ‫من‬ ‫هذهالمجموعة‬ ‫الكولسترول‬ ‫تمنعبشكل‬ ‫تنافسي‬ ‫في‬ ‫األولى‬ ‫الخطوة‬ ‫تخليق‬ ‫الكوليسترول‬ . ‫المختزل‬ . HMG-CoA • ‫بواسطة‬ ‫التفاعل‬ ‫هذا‬ ‫يتمتحفيز‬ ‫إنزيم‬ • ‫لهذا‬ ‫الطبيعية‬ ‫للركيزة‬ ‫هيكلية‬ ‫نظيرات‬ ‫هي‬ ‫أدويةالستاتين‬ HMG-CoA ‫لتثبيط‬ ‫فعال‬ ‫بشكل‬ ‫وتتنافس‬،‫اإلنزيم‬ ‫إنزيم‬ ‫المختزل‬ . • ،‫نوفو‬ ‫دي‬ ‫الكولسترول‬ ‫تخليق‬ ‫تمنع‬ ‫فإنها‬ ،‫بذلك‬ ‫القيام‬ ‫منخالل‬ ‫في‬ ‫الكولسترول‬ ‫مستويات‬ ‫وبالتاليخفض‬ ‫البالزما‬
  • 24. 21 Other examples of competitive inhibitors as drugs  β-lactam antibiotics, such as penicillin and amoxicillin, act by inhibiting enzymes involved in bacterial cell wall synthesis.  Angiotensin-converting enzyme (ACE) inhibitors. They lower blood pressure by blocking the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II. These drugs, which include cause vasodilation and a resultant reduction in blood pressure.  Allopurinol, a drug used to treat gout, decreases urate production by inhibiting xanthine oxidase. - ‫ب‬ - ‫تثبيط‬ ‫طريق‬ ‫عن‬ ،‫واألموكسيسيلين‬ ‫البنسلين‬ ‫مثل‬ ،‫الالكتامية‬ ‫الحيوية‬ ‫المضادات‬ ‫تعمل‬ ‫اإلنزيمات‬ ‫جدار‬ ‫تكوين‬ ‫في‬ ‫المشاركة‬ ‫البكتيرية‬ ‫الخلية‬ . ‫طريق‬ ‫عن‬ ‫الدم‬ ‫ضغط‬ ‫تخفض‬ ‫إنها‬ . ( ACE) – ‫مثبطات‬ ‫اإلنزيم‬ ‫المحول‬ ‫لألنجيوتنسين‬ ‫منعاإلنزيم‬ ‫يقسم‬ ‫الذي‬ ‫األنجيوتنسين‬ 1 ،‫القوي‬ ‫األوعية‬ ‫مضيق‬ ‫ليشكل‬ ‫أنجيوتنسين‬ 2 . ‫وما‬ ‫الدموية‬ ‫األوعية‬ ‫توسع‬ ‫تسبب‬ ‫تشمل‬ ‫والتي‬ ،‫األدوية‬ ‫هذه‬ ‫ينتج‬ ‫عنها‬ ‫من‬ ‫الدم‬ ‫ضغط‬ ‫في‬ ‫انخفاض‬ . - ‫طريق‬ ‫عن‬ ‫اليورات‬ ‫إنتاج‬ ‫من‬ ‫يقلل‬ ،‫النقرس‬ ‫لعالج‬ ‫يستخدم‬ ‫دواء‬ ‫وهو‬،‫الوبيورينول‬ ‫الزانثين‬ ‫تثبيطأوكسيديز‬ . 21
  • 25. 22 Noncompetitive Inhibition A noncompetitive inhibitor • Does not have a structure like substrate • Binds to the enzyme but not active site • Changes the shape of enzyme and active site • Substrate cannot fit altered active site • No reaction occurs • Effect is not reversed by adding substrate ‫مثبط‬ ‫غير‬ ‫تنافسي‬ • ‫ليس‬ ‫لديها‬ ‫الركيزة‬ ‫مثل‬ ‫هيكل‬ • ‫يرتبطب‬ ‫اإلنزيم‬ ً‫ا‬‫نشط‬ ً‫ا‬‫موقع‬ ‫ليس‬ ‫ولكنه‬ • ‫النشط‬ ‫والموقع‬ ‫اإلنزيم‬ ‫يغيرشكل‬ • ‫تغييره‬ ‫تم‬ ‫الذي‬ ‫النشط‬ ‫الموقع‬ ‫تناسب‬ ‫أن‬ ‫للركيزة‬ ‫اليمكن‬ • ‫فعل‬ ‫رد‬ ‫أي‬ ‫اليحدث‬ • ‫بإضافة‬ ‫التأثير‬ ‫عكس‬ ‫اليتم‬ ‫الركيزة‬
  • 26. 23 Examples of noncompetitive inhibitors: • Lead poisoning lead forms covalent bonds with the sulfhydryl side chains of cysteine in proteins. The binding of the heavy metal shows noncompetitive inhibition (covalent bonding). – Ferrochelatase, an enzyme that catalyzes the insertion of Fe2+ into protoporphyrin, is an example of an enzyme sensitive to inhibition by lead. • Other examples of noncompetitive inhibition are certain insecticides, whose neurotoxic effects are a result of their irreversible binding at the catalytic site of the enzyme acetylcholinesterase (an enzyme that cleaves the neurotransmitter, acetylcholine).