Dr.

Mohmmed Qaisiya
Dr. Mohannad Al Jazzar
Protein Functions = Enzymes
Virtually all reactions in the body are mediated by
enzymes

Most enzymes end with -ase = activity

DNA polymerase, kinase, phosphatase,........

Other named by the source or the person who

discovered it. pepsin, papine, trypsin

Enz: Protein catalysts that increase the rate of

reactions without being changed in the overall process
Properties of enzymes

Have an Active site

Have specific location within the cells
 Systematic name
Enzymes are classified by the reactions they catalyze

ATP + D-glucose --> ADP + D-glucose-6-phospate

Systematic name: ATP:glucose phosphotransferase
Classification number: 2.7.1.1.
Hexokinase 2. --> Transferase (class)
7. --> phosphotransferase (subclass)
1. --> phosphotransferase with a hydroxyl group as acceptor
1. --> D-glucose as the phosphoryl group acceptor
 Special pocket or cleft
containing amino acids that
involved in catalysis

Complete, catalytically active enzyme: Holoenzyme

Only protein part (without cofactor and/or coenzyme): Apoenzyme or
Apoprotein
 HOW Enzymes Work ?
✔Enzymes provide an alternate,
energetically favorable reaction
pathway (binding energy) different
from uncatalyzed reaction

✔Hold S in proper orientation

✔On the active sites: chemical reactions

take place between S and E functional
groups

Transition state : High energy intermediate

Free energy of activation : Barrier separating R form P.

Difference in free energy between R and T*
 Factors affect enzymes activity
1. [S] concentration

2- temoerature
3. pH
4. Feedback inhibition
5. Allosteric regulation
6. Modification
 Michaelis-Menten equation
Describes how reaction velocity varies with substrate concentration
 Michaelis-Menten Constant Km
Km is numerically equal to [S]at which the reaction velocity is equal
to 1 ⁄2 Vmax . Km does not vary with the concentration of enzyme.

❖Is characteristic of an enzyme and its particular substrate, and

reflects the affinity of the enzyme for that substrate.

❖Small Km reflects a high affinity of the E for S, because a low

concentration of substrate is needed to reach ½ Vmax

❖Large Km reflects a low affinity of the E for S, because a high

concentration of substrate is needed to reach ½ Vmax
Enzymes are subject to Reversible and Irreversible inhibitors
Irreversible inhibitors: Inhibitors that bind covalently and
destroy the enzyme and its catalytic activity
“Suicide inactivators”

Inhibitor Enzyme inhibited Function

======================================
Sarin Acetylcholinesterase nerve gas

Penicillin Transpeptidase antibiotics

Aspirin Cyclooxygenase NSAID
5FU Thymedylate synthetase anticancer drug
Allpourinol Xanthine oxidase anti gout drug
Deprenyl Dopamine monooxygenase Parkinson’s treatment
 HIV inhibitors (competitive inhibitor)

HIV retrovirus RNA------ cDNA (reverse transcriptase)

Reverse transcriptase inhibitors (AZT)

✔Methotrexate: Anticancer drug.

competitive inhibitor
 Feedback inhibition

Buildup of the end product ultimately

slows the entire pathway

In many pathways a regulatory

step is catalyzed by an Example of heterotropic
allosteric inhibition
allosteric enzyme

Noncompetitive inhibition
Covalent modification = Phosphorylation
 Some irreversible non competitive inhibitors

• Dimercaprol or BAL used in heavy metal poisoning

• Disulfiram anti alcoholism inhibit acetaldehyde
dehydrogenase
• Methotrexate anti cancer inhibit folate reductase
needed for DNA synthesis
• Amphitamine inhibits Mono Amine Oxidase treats
narcolypsy ,mental disorder, depression
• Physostigmine inhibits acetylcholinesterase
• Dicoumarol anti coagulant
• Succinylcholine muscle relaxant.
• Azido di deoxy thymidine ( Zidovodine) anti HIV
 Es and Genetic defect
• Albinism…..tyrosine 3 mono oxygenase
• Taysachs …..hexosaminidase
• Gauchers…..glucosidase
• PKU …….phenyl alanine hydroxylase
• Physical and mental retardation
Proteolytic activation:
Some enzymes are synthesized as larger inactive precursor forms
called proenzymes or zymogens.

Activation involves the irreversible hydrolysis of one or more peptide

bonds, resulting in an active form.
 Enzymes in clinical diagnosis

• Isozyme: multi forms of an enzyme with different catalytic

subunits that differ in amino acid sequence but catalyze the
same chemical reaction. Example LDH
• Anti enzymes: chemicals produced from helminthes that
inactivate or inhibit the small intestine enzymes
• Abzymes = activity of an antibodies and enzyme (ex. HRP)
 Es in Clinical diagnosis and Treatment
Prostate cancer prostate serum antigen PSA Acid phosphatase

Liver/bone disorders Alkaline phosphatase

Hepatitis Alnine aminotransferase

Pancreatitis Amylase

Heart attack Lactate dehydrogenase

Troponin creatine
phosphate
To treat Myocardial infarction, thrombosis Streptokinase
Clexan , Plavix
To treat Acute leukemia L- asparaginase