كيمياء سريرية المحاضرة 2

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Medical enzymes

* Enzymes play an important role in Metabolism,


Diagnosis, and Therapeutics.
* All biochemical reactions are enzyme catalyzed
in the living organism.
* Level of enzyme in blood are of diagnostic
importance e.g. it is a good indicator in disease
such as myocardial infarction.
* Enzyme can be used therapeutically such as
digestive enzymes.
* Enzymes are proteins that increase the rate of
reaction by lowering the energy of activation

* They catalyze nearly all the chemical reactions


taking place in the cells of the body.

* Not altered or consumed during reaction.

* Reusable.
ENZYME CLASSIFICATION
TRANSFERASE (HEXOKINASE)
(2) OXIDOREDUCTASE (ALCOHOL
DEHYDROGENASE)
(3) HYDROLASE (ATPase)
(4) LYASE (PYRUVATE DECARBOXYLASE)
(5) LIGASE (PYRUVATE CARBOXYLASE)
(6) ISOMERASE (MALEATE ISOMERASE)
(7) HYDROLASE (PHOSPHOENOL PYRUVATE
CARBOXYKINAS)
-Active site :
The area on the enzyme where the
substrate or substrates attach to is
called the active site.
Enzymes are usually very large proteins and the
active site is just a small region of the enzyme
molecule.
In the lock-and-key model of enzyme action:

This explains enzyme specificity


This explains the loss of activity when
enzymes denature
-The Induced Fit Hypothesis :
• Some proteins can change their shape
(conformation)
• Substrate + enzyme, induces a change in
the enzyme’s conformation
Structure of enzymes
Enzymes

Complex or holoenzymes (protein Simple (only protein)


part and nonprotein part – cofactor)

Apoenzyme (protein
part) Cofactor

Prosthetic groups Coenzyme


-usually small inorganic -large organic
molecule or atom; molecule
-usually tightly bound -loosely bound to
to apoenzyme apoenzyme
- Factors affecting Enzymes

• substrate concentration
• pH
• temperature
• inhibitors.
Enzymes routinely measured
NAME OF THE ENZYME PRESENT IN

Aspartate Amino transferase (AST) Heart and Liver


Or glutamate-oxaloacetate transaminase
(SGOT)
Alanine Amino transferase (ALT) Heart and Liver
or glutamate-pyruvate transaminase
(SGPT)
Alkaline Phosphatase (ALP) Bone, intestine and other tissues
Acid Phosphatase (ACP) Prostate
 glutamyl Transferase ( GT) Liver
Creatine kinase (CK) Muscle Including cardiac muscle
Lactate Dehydrogenase (LDH) Heart, liver, muscle, RBC
 Amylase Pancreas
Measurement of enzyme activity
• Enzyme activity is expressed in
International unit (IU)
It corresponds to the amount of enzymes that
catalyzes the conversion of one micromole (mol)
of substrate to product per minute
CREATINE KINASE (CK)

Creatine + ATP CK posphocreatine + ADP


(Phosphocreatine – serves as energy reserve during muscle
contraction)
▪ Creatine kinase is a dimer made of 2 monomers
occurs in the tissues
▪ Skeletal muscle contains M subunit, Brain contains
B subunits
▪ Three different isoenzymes are formed
LACTATE DEHYDROGENASE (LDH)

Pyruvate Lactate (anaerobic glycolysis)


▪ LDH is elevated in myocardial infarction, blood disorders
▪ It is a tetrameric protein and made of two types of subunits
namely H = Heart, M = skeletal muscle
▪ It exists as 5 different
isoenzymes with various
combinations of H and M subunits
ALANINE TRANSAMINASE (ALT) AND ASPARTATE
TRANSAMINASE( AST)

- Oxoglutarate + L-aspartate - Oxoglutarate + L-alanine


Aspartate Alanine
aminotransferase aminotransferase
(AST) (ALT)
L- glutamate + oxaloacetate L - glutamate + pyruvate
 Alanine transaminase (ALT) and Aspartate transaminase (AST) enzymes are
the most abundantly present in the liver and is elevated in blood as a result of
leakage from damaged cells
 Measurement of these transaminases is useful for the diagnosis
of liver diseases
 In viral hepatitis the enzyme levels are increased 20-50 times
above the upper limit of the normal range
 Alanine transaminase (ALT) increase is specific for liver
damage involving hepatocellular damage
 Aspartate transaminase (AST) is moderately increased in
Muscular dystrophy and acute myocardial infarction
ALKALINE PHOSPHATASE (ALP)

* Is a group of enzymes that have maximal activity at a


high pH 9.0-10.5
* Widely distributed throughout the body
* High levels are seen is liver, bone, placenta and
intestine and useful to assess hepatobiliary and bone
diseases
CREATINE KINASE (CK)
Creatine + ATP phosphocreatine + ADP
(Phosphocreatine – serves as energy reserve during muscle
contraction)
▪ Creatine kinase is a dimer made of 2 monomers
occurs in the tissues
▪ Skeletal muscle contains M subunit, Brain contains
B subunits
▪ Three different isoenzymes are formed
AMYLASE
- Is the digestive enzymes from the pancreas and salivary
glands to digest complex carbohydrates.
- Elevated in acute pancreatitis.
- It is used as a marker to detect acute pancreatitis,
appendicitis.
Acid phosphatase :
- Is a group of enzymes that have maximal activity at pH 5.0-
6.0

- It is present in prostate gland, liver, spleen and RBC.

- The main source of ACP is prostate gland and so can be


used as a marker for prostate disease.
 glutamyltransferase ( GT)
Amino acid + Glutathione 
( GT)
-glutamyl amino acid +
Cysteinylglycine

It is involved in amino acid transport across the membranes.


Found mainly in biliary ducts of the liver, kidney and pancreas.
Enzyme activity is induced by a number of drugs and in particular
alcohol.

-GT increased in liver diseases especially in obstructive jaundice.


-GT levels are used as a marker of alcohol induced liver disease and in
liver cirrhosis.

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