1. Enzymes
Biochemistry
(BMS)
L.Noha Soliman

2. Objectives Enzyme Regulation: Enzymes as diagnostic tools.
1. Feedback control.
2. Proenzymes.
3. Isoenzymes.
Enzymes as diagnostic tools.

3. Enzyme Regulation 1. Feedback control:
Regulation process where the product of a series of enzyme-catalyzed reactions inhibits an earlier reaction in the sequence.

4. Enzyme Regulation 2. Proenzymes (Zymogens):
They are inactive precursors of enzymes.
Most digestive and blood-clotting enzymes exist in the zymogen form, until activated.
Must have polypeptide chain portion removed otherwise not active.

5. Enzyme Regulation 2. Proenzymes (Zymogens):
Ex. Trypsin ( Digestive enzyme):
Synthesized and stored as trypsinogen. No enzyme activity.
Active only after a six- amino acid fragment is removed.
Removal of amino acid fragment changes primary and tertiary structure Active form.

6. Enzyme Regulation 3.Isozymes or Isoenzymes:
Different form of the same enzyme.
They perform the same catalytic function.
(Catalyze same reactions but are formed from structurally different polypeptides).
Different Isoenzymes may arise from different tissues and their specific detection may give clues to the site of pathology.

7. ENZYMES AS
DIAGNOSTIC
TOOLS

8. How? The measurement of the serum levels
of numerous enzymes has been shown
to be of diagnostic significance.
This is because the presence of these enzymes in the serum indicates that
tissue or cellular damage has occurred resulting in the release of intracellular components into the blood &this increases the level of certain enzymes in blood according to the damaged organ.

9. Information from enzymes measurements in serum?
Presence of disease.
Organs involved.
Etiology /nature of disease: differential diagnosis.
Extent of disease-more damaged cells-more leaked enzymes in blood.

10. 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.

11. What are the enzymes most usedin
the diagnosis of
certain diseases?

12. **For example:- Plasma enzymes Functional Non functional Isoenzymes
1-Lactate dehydrogenase(LDH)
2-Creatine kinase(CK)
Isoenzymes
3-Alanine transaminase(ALT) 4-Aspartate transaminase(AST)
5-Alkaline phosphatase Acid phosphatase
7-Amylase & Lipase enzymes

13. Lactate dehydrogenase
(LDH)
Lactic acid
Pyruvic acid
NAD
NADH+H
LDH is elevated in myocardial infarction, blood disorders.
It is a tetramer 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.

14. Lactate dehydrogenase
isoenzymes
Isoenzyme name
Composition
Present in
Elevated in
LDH1
( H4)
HHHH
Heart, RBC
myocardial infarction
LDH2
(H3M1)
HHHM
LDH3
(H2M2)
HHMM
lungs and spleen
leukemia
LDH4
(H1M3)
HMMM
viral hepatitis
LDH5
(M4)
MMMM
Skeletal muscle, Liver
Skeletal muscle
and liver diseases

16. Creatine kinase (CK) Creatine Creatine phosphate
ATP
ADP
(Phosphocreatine – serves as energy reserve during muscle contraction)
Creatine kinase is a dimer made of 2 monomers.
Skeletal muscle contains M subunit, Brain contains B subunits.
Three different isoenzymes are formed.

17. Creatine kinase (CK) isoenzymes
Isoenzyme name
Composition
Present in
Elevated in
CK-1 BB
Brain
CNS diseases
brain tumors
CK-2 MB
Heart
Acute myocardial infarction
CK-3 MM
Skeletal muscle
Skeletal muscle diseases

19. Alanine transaminase (ALT)
It is also called
Serum glutamic pyruvic transaminase(SGPT).
This enzyme is found predominantly in hepatocytes.
It increases in liver & heart diseases.
ALT is more specific for liver disease than AST.

20. Aspartate transaminase
(AST)
It is also called
Serum glutamic oxaloacetic transaminase(SGOT)
It increases in liver & heart diseases.

22. **It is found in the bone , liver, intestine, placenta.
Alkaline phosphatase
**It is found in the bone , liver, intestine, placenta.
**Increases mainly in bone and liver diseases.
Acid phosphatase
**is found in the prostate, red blood cells, bone, liver, and pancreas.
** Mostly used to detect prostatic carcinoma.
Amylase and lipase enzymes increase in diseases of the pancreas as acute pancreatitis.

23. Summary-Enzymes as diagnostic markers
Major diagnostic use
Origin
Enzyme
Myocardial infarction
Heart, liver, muscle, RBC
Lactate dehydrogenase (LDH)
Muscle disease
Skeletal Muscle
Heart Muscle
Brain
Creatine kinase (CK)
Viral hepatitis
Heart and Liver
Alanine aminotransferase (ALT) Serum glutamate-pyruvate transaminase (SGPT)
Liver and heart disease
Aspartate aminotransferase (AST)
Serum glutamate-oxaloacetate transaminase (SGOT)
Liver and bone disease
Hepatobiliary tree Bone, placenta
Alkaline phosphatase (ALP)
Prostate cancer
Prostate, erythrocytes
Acid phosphatase (ACP)
Acute pancreatitis
Pancreas, Salivary glands
Amylase
Pancreas
Lipase

24. Many
THANKS