ENZYMES IN MEDICINE - PowerPoint PPT Presentation

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ENZYMES IN MEDICINE

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ENZYMES IN MEDICINE Diagnostic indicators the activities of many enzymes are routinely determined in plasma ( rarely in tissue biopsies) for diagnostic purposes ... – PowerPoint PPT presentation

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Title: ENZYMES IN MEDICINE


1
ENZYMES IN MEDICINE
2
  • Diagnostic indicators the activities of many
    enzymes are routinely determined in plasma (
    rarely in tissue biopsies) for diagnostic
    purposes in diseases of the heart, liver,
    skeletal muscle, pancreas and other tissues -
    enzyme diagnostics
  • Therapeutic agents several enzymes are used as
    drugs new approach - enzymotherapy
  • Diagnostic tools use as chemicals in clinical
    laboratory assays

3
ENZYMES IN CLINICAL DIAGNOSIS
  • secretory - produced by tissues
    (namely liver), acting in plasma

    prothrombin, plasminogen, cerruloplasmin,
    choline
    esterase lipoprotein lipase
  • Enzymes
  • intracellular function
    intracellulary, have no physiological use in
    plasma
  • - membrane
    bound ALP, GMT
  • - cytosolic
    ALT, AST, LD, MDH
  • -
    mitochondrial AST, GMDH
  • -
    lysosomal - ACP
  • - tissue specific
    glucose-6-phosphatase liver

  • amylase pancrease

  • LD1 heart

4
  • Healthy individuals - levels of intracellular
    enzymes fairly constant, low
  • the rate of enzyme release from damaged
    cells into plasma balanced by the rate of removal
    of enzyme protein from plasma
  • ?
  • Physiological enzyme levels ? reference
    values of the enzyme activities

  • (determined in clinical laboratory each
    lab
    has its own reference values)

  • Elevated enzyme activity in the plasma reflect
    tissue damage accompanied by increased release of
    intracellular enzyme
  • Skeletal muscle during exertion
    physiologically elevated levels of muscle enzymes
    in plasma
  • Many diagnostically important enzymes
    isoenzymes pattern of isoenzymes in plasma
    (determined electroforetically)
  • a means of identifying the damaged
    tissue

5
ALTERATION OF ENZYME PLASMA LEVELS
  • Increased values increased cell membrane
    permeability


  • anoxia, disturbances of energy metabolism ?

  • cytosolic enzymes ALT, LD, CK
  • - cell
    necrosis ? membrane-bound enzymes ALP, GMT

  • mitochondrial enzymes AST,
    GMDH
  • -
    induction of the enzyme synthesis ? drugs ALP,
    GMT
  • Decreased values inhibition of the activity ?
    drugs
  • -
    inhibition of the synthesis ? cell damage, drugs

6
Examples of enzymes commonly assayed for
diagnostic purposes
  • Enzyme
    Location Cause of elevated
    plasma level
  • Acid phosphatase - ACP Prostate
    Prostatic cancer
  • Alkaline phosphatase ALP Bone, liver
    Rickets, hypoparathyroidism,


  • osteomalacia, obstructive


  • jaundice, cancer of bone/liver
  • Alanine aminotransferase ALT Liver (muscle,
    Hepatitis, jaundice, circulatory

    heart, kidney) faillure with liver
    congestion
  • Aspartate aminotransferase AST Heart, muscle,
    Myocardial infarction, muscle

    red cells, liver damage, anemia,
    hepatitis,


  • circulatory faillure with liver


  • congestion
  • Amylase - AM
    Pancres Acute pancreatitis,
    peptic ulcer
  • ?-Glutamyl transferase GMT Liver,
    kidney, Hepatitis, alcoholic liver

  • pancreas damage,
    cholestasis

7
Examples of isoenzymes commonly assayed for
diagnostic purposes
  • Enzyme
    Location Cause of elevated
    plasma level
  • Creatine kinase CK
  • CK-MB
    Heart Myocardial
    infarction
  • CK-MM
    Skeletal muscle Muscular dystrophy
  • Lactate dehydrogenase LD
  • LD1 gt LD2
    Heart, kidney, Myocardial infarction,
    kidney

  • blood cells disease,
    megaloblastic anemia,

    leukemia
  • LD2, LD3

    Leukemia
  • LD5
    Liver, muscle Liver disease,
    muscle damage

8
ENZYMES IN THERAPY
  • Substitution of missing production of digestive
    enzymes digestive enzymes pepsin trypsin
  • Removal of deposits of death tissue or fibrin
    (e.g. in lungs, eyes), treatment of skin defects
    proteinases, nucleases, collagenase
  • Acceleration of fibrinolysis in lungs
    embolization (activation of plasmin and
    plasminogen) streptokinase, urokinase

9
ENZYMOTHERAPY
  • Orally administered enzymes treatment of a
    variety disorders

  • - digestive, gastrointestinal, pancreatic

  • - inflammatory diseases, edema

  • - immune and autoimmune diseases
    (arthritis,
    multiple sclerosis)

  • - viral diseases (herpes, AIDS)

  • - cancer
  • Mixtures of enzymes of plant and/or animal
    origin - proteinases, amylase, lipase -
    administered as acidoresistent tablets
  • Pancreatin trypsin, chymotrypsin, lipase,
    amylase
  • Wobenzym pancreatic and plant proteolytic
    enzymes trypsin,
    chymotrypsin, papain (Carica papaya), bromelain
    (ananas) combination of
    enzymes with different specificity, pH optimum,
    stability, interaction with
    inhibitors and antiproteinases

  • ? multiple action

10
  • Mechanism of resorption (transport of large
    macromolecules across the intestinal barrier)
    paracellular transport, receptor mediated
    endocytosis and transcytosis
  • Mechanism of action interaction with plasma
    antiproteinases

  • ?1-antitrypsin, ?2-macroglobulin ?complexes
  • direct proteolytic
    action, degradation of adhesive
  • molecules, secretion of
    cytokins (tranforming growth factor
    TGF-?), modulation of receptor function
  • not
    fully clarified

?
11
ENZYMES - USE IN LABORATORY ASSAYS
  • Enzymes isolated from different sources - used
    for determination of various substances in
    the blood, plasma/serum and urine ? enzyme
    methods
  • much more specific than
    chemical methods, the presence of relative
    substances with similar chemical
    properties does not hinder
  • Components of commercial kits or
    diagnostic strips
  • - determination of glucose - glucose
    oxidase, peroxidase
  • cholesterol
    - cholesterol esterase, cholesterol oxidase

  • peroxidase,
  • urea
    urease, . in blood, plasma, serum
  • - proof of glucose (glucose oxidase), ..
    in blood or urine (strips)
  • Markes in the immunochemical analysis
  • - ELISA (enzyme-linked immunoadsorbent
    assay) peroxidase, alkaline

    phosphatase

12
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13
NUCLEOTIDESStructure, Function
14
NUCLEOTIDE STRUCTURE
  • Nucleotides
  • nitrogenous base pentose
    phosphate group(s)
  • purine ribose
    1 - 3
  • pyrimidine deoxyribose
  • other (nicotinamide)
  • Nucleosides

15
THE NITROGENOUS BASES
Purine bases
adenine
guanine
Pyrimidine bases
cytosine
thymine
uracil
16
NUCLEOSIDE
  • A sugar - base combination.

Base
?-N-glycosidic linkage
N
Sugar In this case deoxyribose
17
thymine
uracil
O
O
H
HOCH2
HOCH2
OH
uridine
deoxythymidine
cytosine
HOCH2
OH
cytidine
18
guanine
adenine
HOCH2
HOCH2
OH
guanosine
deoxyadenosine
hypoxanthine
!
HOCH2
inosine
OH
19
NUCLEOTIDES
  • 5-OH on the sugar of a nucleoside is converted
    into a phosphate ester.

deoxyadenosine monophosphate (dAMP)
Each is named based on sugar and base name and
then the number of phosphates is indicated.
20
  • ATP - adenosine triphosphate

AMP
ADP
ATP
21
NUCLEOTIDE FUNCTION
  • Precursors of DNA, RNA - NTPs
  • Energy transport - ATP
  • Allosteric effectors of enzymes ATP, ADP, AMP
  • Covalent modification of enzymes ATP
  • Intracellular mediators ( second messengers)
    cAMP, cGMP
  • Coenzymes NAD, NADP, FAD, CoA-SH
  • Activated precursors of polysaccharaides,
    glycoproteins, proteoglycans, phospholipids,
    glycolipids UDPG, UDPGA, UDPGal, CDP-choline,
    CDP-diacylglycerol
  • Active groups (group transport) SAM, PAPS

22
NAD
reactive site
nicotinamide
adenine
ribose
23
FAD
24
Coenzyme A
25
CH
OH
2
H
O
H
H
H
OH
OH
OH
OH
H
26
H
O
O
C
C
H
O
C
H
O
C
O
-O-
O
CH2
P
-
O
Non-polar tail
27
cAMP cyclic adenosine monophosphate
cAMP
28
CH2
O
O
P
O
O
O-
  • cAMP cyclic adenosine monophosphate
  • intracellular mediator, second messenger of
    hormonal signal tranduction
  • via adenylate cyclase cascade
  • - mechanism of action allosteric effector

29
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