Clinical Importance of Enzymes - AIIMS RISHIKESH · Detection of Enzymes for diagnosis or prognosis...
Transcript of Clinical Importance of Enzymes - AIIMS RISHIKESH · Detection of Enzymes for diagnosis or prognosis...
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Clinical Importance
of Enzymes
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Clinical Importance of Enzymes
Disorders
Diagnosis of Diseases
Pharmacologic agents and Gene Therapy
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Enzymatic Diseases
• Thousand of diseases occurs due to enzymatic defects
• Most of them are rare and inherited
- May affect Metabolic pathways: carbohydrate, lipid, proteins
- May affect Physiological processes like digestion
- May affect circulating enzyymes like antiproteases
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Phenyl ketonuria
Phenylalanine
Tyrosine
1 in 10000 live births
Mental Retardation
Albinism
Phenylalanine Hydroxylase
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Lactase Deficiency
• A very common disorder
• Milk indigestion
• Characterized by bloating, abdominal cramps and diarrhoea
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Emphysema
• Due to α 1 antitrypsin deficiency
• Inhibitor of serine protease- Elastase
• Neutrophilic elastase inhibits bacterial growth
• Elastase may damage lung tissue elastin if escapes
• Kept in check by antiprotease α 1 antitrypsin
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Diagnostic utility
Detection of Enzymes for diagnosis or prognosis of disease
Enzymes as analytical agent
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Detection of Enzymes for diagnosis of
disease
Disorders Enzymes
Liver Function Tests SGOT, SGPT, ALP, GGT
Cardiac Function Tests CK-MB, Troponins
Pancreatic Enzymes Amylase, Lipase
Muscle Enzymes CK, LDH
Bone Enzymes ALP , ACP
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Plasma Functional Enzyme vs Plasma
Nonfunctional enzymes
Plasma functional Enzyme
• Present in blood at all times
• Perform physiological functions in
blood
• Eg. Lipoprotein lipase,
Pseudocholinesterase, Clotting factors
• Decrease in diseased conditions like
Liver disease
Plasma non-functional Enzymes
• Present in blood in minimal amounts
• No known physiological function in blood
• Eg. SGOT, SGPT, Amylase, CK-MB
• Increased in diseased conditions due to
tissue damage, altered enzyme production
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Isoenzymes
• Multiple forms of enzymes that catalyze the same reaction but differ in their structure
• Encoded by different structural gene loci
• Differ in physical properties like electrophoretic motility or resistance to heat inactivation
• Antigenically distinct
• Differ in catalytic properties like Km, Vmax.
• Shows Tissue specific distribution.
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Examples of Isoenzymes
Enzyme Isoenzymes
CK CK-1 (CK-MM), CK-2 (CK-MB), CK-3 (CK-BB)
LDH LDH 1-5
ALP Hepatobiliary, Bone, Intestinal, Placental
Hexokinase Hexokinase I-IV
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Methods for Iso-enzyme detection
• Electrophoresis
• ELISA/Ag-Ab reactions
• Sequencing
• Susceptibility to Inhibitors/ Inactivation
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Clinical Scenario 1
Jaundice
• A 69 years old male presented with abdominal pain. His LFTs showed
following results. His sclera was yellow and stools were pale with dark
colored urine.
Tests Result Reference Range
Bilirubin 6.0mg/dl 0.3-1.2mg/dl
AST 34 U/L <50 U/L
ALT 35 U/L <50 U/L
ALP 870 U/L 30 – 120 U/L
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Clinical Scenario 2
Jaundice
• A 35 years old male presented with malaise, weight loss, generalized
weakness. He noticed dark colored urine for past 2 days. LFTs were as
follows
Tests Results Reference Range
Bilirubin 2.5 mg/dL 0.3-1.2mg/dl
AST 900 U/L <50 U/L
ALT 1200 U/L <50 U/L
ALP 370 U/L 30 – 120 U/L
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Clinical scenario 3
MI
• A 50 year male presented to ED with tight chest pain radiating to left arm.
Cardiac function tests were as follows
Tests Results Reference Range
CK-Total 235 U/L < 145 U/L
CK-MB 50 U/L < 24 U/L
Troponin T 15 ng/L < 10 ng/L
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Enzymes as analytical reagents
• Measurement of Metabolites: Uricase, Urease, Glucose oxidase
• Immunoassays: ALP, Horse radish peroxidase, glucose 6 phosphate
dehydrogenase
• Recombinant DNA Technology: Restriction Endonuclease, DNA ligase,
DNA polymerase
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Therapeutics
• Various drugs are used to inhibit enzymes therapeutically
Disorder Enzyme Drug
Cancer Thymidylate Synthetase 5 fluorouracil
Inflammation Cyclooxygenase Aspirin
Gout Xanthine oxidase Allopurinol
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Therapeutics
• Enzymes are also used as drugs
Disorder Enzyme as Drug
MI Streptokinase, tPA ( Thrombolysis)
Gaucher’s disease Glucocerebrosidase (ERT/Gene Therapy)
Cystic Fibrosis Trypsin
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Summary
Disorders: Metabolic Pathways, Digestion, Circulating Enzymes
Diagnosis of Diseases: Biomarkers, Analytical agents, Recombinant DNA technology
Pharmacologic agents and Gene Therapy