(CL8) Enzymes in Medicine

Enzymes In Medicine
Prof Dr Yasmin Anum

Dr. Goon Jo Aan
Dept. of Biochemistry
Objectives
– Explain functional and non-functional plasma

enzymes
– Explain the use of measuring plasma enzyme
activities in diagnosis
– Explain the use of enzymes in medicine
How are enzymes used to promote human
health?
• Provide information on the presence or severity
of disease
• Monitoring patient’s response to therapy
• Diagnostic agent
• Therapeutic agent
Clinical Applications of Enzymes
• 2 types of plasma enzyme:

– Normally present (functional)
– Released from tissues/ cells (no functional
values, present in very low values, important
for diagnostic purposes)
• Released by damaged cells
• Abnormal increase in concentration in cells
Enzymes-isoenzymes commonly
used in the diagnosis of
• Heart Disease
• Liver Disease
• Bone Disease
• Muscle Disease
Measurement of serum enzymes
! Enzymes are normally intracellular and LOW
concentration in blood
! Enzyme release (leakage)in the blood indicates cell damage
(cell –death, hypoxia, intracellular toxicity)
! Quantitative measure of cell/tissue damage
! Fairly non invasive - possible to do repeated tests
Organ specificity- but not absolute specificity
Most enzymes are present in most cells-differing
amounts
Information from enzymes
measurements in serum
! Presence of disease
! Organs involved
! Extent of disease-more damaged cells-more
leaked enzymes in blood
! Time course of disease
Enzymes routinely measured
NAME OF THE ENZYME PRESENT IN Diagnostic test for
Aspartate Amino transferase Heart and Liver Heart disease

(AST) Liver disease: hepatitis B,
C, liver cirrhosis
Alanine Amino transferase (ALT) Heart and Liver Liver disease eg

hepatitis B, C
Alkaline Phosphatase (ALP) Bone, intestine and other Bone disease, and in
tissues obstructive liver disease
Acid Phosphatase (ACP) Prostate Prostate cancer
γ glutamyl Transferase (γ GT) Liver Liver disease, eg
alcoholic cirrhosis
Creatine kinase (CK) Muscle Including cardiac
muscle
Lactate Dehydrogenase (LDH) Heart, liver, muscle, RBC Heart
α Amylase Pancreas pancreatitis
Isoenzymes
• catalyse same reactions but are formed from structurally
different polypeptides.
• They perform the same catalytic function.
• Different isoenzymes may arise from different tissues and
their specific detection may give clues to the site of
pathology.
• Various isoenzymes of an enzyme can differ in three major
ways:
- enzymatic properties (Kinetics, electrophoresis)
- physical properties (e.g heat stability)
- biochemical properties such as amino acid sequence and
immunological reactivities.
Isoenzymes
• Glucokinase and Hexokinase are typical
examples of isoenzymes, both catalyze the
same reaction
Glucose + ATP " Glucose 6 (P) + ADP
• There are four Hexokinases: I, II, III and IV.
Hexokinase I is present in all mammalian
tissues, and Hexokinase IV, aka Glucokinase, is
found mainly in liver, pancreas and brain
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 (µmol)
of substrate to product per minute
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
Isoenzyme Composition Composition Present in
LDH1 ( H4) HHHH Myocardium,

RBC
LDH2 (H3M1) HHHM Myocardium,

RBC
LDH3 (H2M2) HHMM Kidney,

Skeletal
muscle
LDH4 (H1M3) HMMM Kidney,
Skeletal
muscle
LDH5 (M4) MMMM Skeletal
muscle, Liver
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
Isoenzyme Composition Present in
CK-1 BB Brain
Myocardium
CK-2 MB
/ Heart
Skeletal
CK-3 MM muscle,
Myocardium
Cardiac markers pattern in MI
AST
ENZYME IDENTIFICATION IN LIVER DISEASE
ALANINE TRANSAMINASE (ALT) AND ASPARTATE
TRANSAMINASE( AST)
α- Oxoglutarate + L-aspartate α- Oxoglutarate + L-alanine
Aspartate Alanine
aminotransferase (AST) aminotransferase
(ALT)
L- glutamate + oxaloacetate L - glutamate + pyruvate
$ Alanine transaminase (ALT) and Aspartate transaminase (AST) enzymes
are the most abundantly present in the liver
$ elevated in blood as a result of leakage from damaged cells
$ Measurement is useful for the diagnosis of liver diseases
$ 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
LEVELS OF ENZYMES IN DISEASES
INVOLVING LIVER DAMAGE
In viral hepatitis
Rapid rise in serum AST
& ALT even before
bilirubin rise is seen
ALKALINE PHOSPHATASE (ALP)-for liver
disease and bone disease
$ High levels in liver, bone, placenta and intestine
$ useful to assess hepatobiliary and bone diseases

$ High levels of ALP is indicative of obstruction of the bile duct
due to gallstones or tumour
$ In bones, the enzyme is derived from osteoblasts.
$ Hence increased in bone diseases like rickets, osteomalacia,
neoplastic diseases with bone metastases
ACID PHOSPHATASE (ACP)
$ present in prostate gland, liver, spleen and RBC.
$ main source of ACP is prostate gland
$ marker for prostate disease.
AMYLASE
$ digestive enzymes from the pancreas and salivary glands
$ elevated in acute pancreatitis

γ glutamyltransferase (γ GT)
Amino acid + Glutathione γ - glutamyl amino acid +
Cysteinylglycine
$ Found mainly in biliary ducts of the liver, kidney and pancreas.

$ Enzyme activity is induced by some drugs and alcohol
$ γ -GT increased in liver diseases especially in obstructive
jaundice
$ γ -GT levels are used as a marker of alcohol induced liver
disease and liver cirrhosis.
Use in clinical tests
• Determination of glucose: use glucose strip
with glucose oxidase
• Determination of cholesterol : use cholesterol
esterase
• Markers or detection agents in ELISA
ELISA-Enzyme Linked
ImmunoSorbent Assay
horseradish peroxidase (HRP) and alkaline phosphatase

(AP) used as detection agent

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Enzymes In Medicine

Prof Dr Yasmin Anum

– Explain functional and non-functional plasma

• 2 types of plasma enzyme:

Aspartate Amino transferase Heart and Liver Heart disease

Alanine Amino transferase (ALT) Heart and Liver Liver disease eg

Pyruvate Lactate (anaerobic glycolysis)

LDH1 ( H4) HHHH Myocardium,

LDH2 (H3M1) HHHM Myocardium,

LDH3 (H2M2) HHMM Kidney,

Creatine kinase is a dimer made of 2 monomers

$ useful to assess hepatobiliary and bone diseases

$ present in prostate gland, liver, spleen and RBC.

$ main source of ACP is prostate gland

$ marker for prostate disease.

$ elevated in acute pancreatitis

$ Found mainly in biliary ducts of the liver, kidney and pancreas.

horseradish peroxidase (HRP) and alkaline phosphatase

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