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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
.

5. Examples
 digestion
 synthesis
+
+

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

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

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

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).