Download MBBS Biochemistry PPT 11 Clinical Importance Of Enzymes Lecture Notes

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Clinical Importance of Enzymes

Disorders

Diagnosis of Diseases

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Pharmacologic agents and Gene Therapy
Enzymatic Diseases

? Thousand of diseases occurs due to enzymatic defects

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? 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

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Phenylalanine Hydroxylase

Tyrosine

1 in 10000 live births

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Mental Retardation
Albinism
Lactase Deficiency

? A very common disorder

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? Milk indigestion
? Characterized by bloating, abdominal cramps and diarrhoea

Emphysema

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? Due to 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 1 antitrypsin

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Diagnostic utility

Detection of Enzymes for diagnosis or

prognosis of disease

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Enzymes as analytical agent

Detection of Enzymes for diagnosis of

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disease

Disorders

Enzymes

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Liver Function Tests

SGOT, SGPT, ALP, GGT

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Cardiac Function Tests

CK-MB, Troponins

Pancreatic Enzymes

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Amylase, Lipase

Muscle Enzymes

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CK, LDH

Bone Enzymes

ALP , ACP

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Plasma Functional Enzyme vs Plasma

Nonfunctional enzymes

Plasma functional Enzyme Plasma non-functional Enzymes

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? Present in blood at all times

? Present in blood in minimal amounts

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? Perform physiological functions in

? No known physiological function in blood

blood

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? Eg. SGOT, SGPT, Amylase, CK-MB

? Eg. Lipoprotein lipase,

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? Increased in diseased conditions due to

Pseudocholinesterase, Clotting factors

tissue damage, altered enzyme production

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? Decrease in diseased conditions like

Liver disease

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Isoenzymes

? Multiple forms of enzymes that catalyze the same reaction but differ in their

structure

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? Encoded by different structural gene loci
? Differ in physical properties like electrophoretic motility or resistance to heat

inactivation

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? Antigenically distinct
? Differ in catalytic properties like Km, Vmax.

? Shows Tissue specific distribution.

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Examples of Isoenzymes

Enzyme

Isoenzymes

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CK

CK-1 (CK-MM), CK-2 (CK-MB), CK-3 (CK-BB)

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LDH

LDH 1-5

ALP

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Hepatobiliary, Bone, Intestinal, Placental

Hexokinase

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Hexokinase I-IV

Methods for Iso-enzyme detection

? Electrophoresis

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? ELISA/Ag-Ab reactions
? Sequencing
? Susceptibility to Inhibitors/ Inactivation
Clinical Scenario 1

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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

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colored urine.

Tests

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Result

Reference Range

Bilirubin

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6.0mg/dl

0.3-1.2mg/dl

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AST

34 U/L

<50 U/L

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ALT

35 U/L

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<50 U/L

ALP

870 U/L

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30 ? 120 U/L
Clinical Scenario 2

Jaundice

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? A 35 years old male presented with malaise, weight loss, generalized

weakness. He noticed dark colored urine for past 2 days. LFTs were as

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follows

Tests

Results

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Reference Range

Bilirubin

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2.5 mg/dL

0.3-1.2mg/dl

AST

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900 U/L

<50 U/L

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ALT

1200 U/L

<50 U/L

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ALP

370 U/L

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30 ? 120 U/L

Clinical scenario 3

MI

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? A 50 year male presented to ED with tight chest pain radiating to left arm.

Cardiac function tests were as follows

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Tests

Results

Reference Range

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CK-Total

235 U/L

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< 145 U/L

CK-MB

50 U/L

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< 24 U/L

Troponin T

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15 ng/L

< 10 ng/L
Enzymes as analytical reagents

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? Measurement of Metabolites: Uricase, Urease, Glucose oxidase
? Immunoassays: ALP, Horse radish peroxidase, glucose 6 phosphate

dehydrogenase

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? Recombinant DNA Technolog y: Restriction Endonuclease, DNA ligase,

DNA polymerase

Therapeutics

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? Various drugs are used to inhibit enzymes therapeutically

Disorder

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Enzyme

Drug

Cancer

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Thymidylate Synthetase

5 fluorouracil

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Inflammation

Cyclooxygenase

Aspirin

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Gout

Xanthine oxidase

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Allopurinol
Therapeutics

? Enzymes are also used as drugs

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Disorder

Enzyme as Drug

MI

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Streptokinase, tPA ( Thrombolysis)

Gaucher's disease

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Glucocerebrosidase (ERT/Gene Therapy)

Cystic Fibrosis

Trypsin

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Summar y

Disorders: Metabolic Pathways, Digestion, Circulating

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Enzymes

Diagnosis of Diseases: Biomarkers, Analytical agents,

Recombinant DNA technology

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Pharmacologic agents and Gene Therapy