The document discusses the role of serum enzyme measurements in diagnosing various diseases, particularly those related to cardiac and gastrointestinal conditions, highlighting enzyme release as an indicator of cell damage. It details specific enzymes and their time courses in heart diseases, including troponin and BNP as markers for myocardial infarction and heart failure. Additionally, it covers the significance of other enzymes in liver function tests and therapeutic applications, emphasizing that these biochemical markers are crucial for assessing disease presence, severity, and prognosis.

1. TAPESHWAR YADAV
P.G Final Year
Department Of Biochemistry
Mamata Medical College-Khammam, A.P, INDIA

2. Measurement of serum enzymes
Diagnostic enzymology
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
Organ specificity- but not absolute specificity inspite of same
gene content.
 Most enzymes are present in most cells-differing amounts

3. Information from enzymes
measurements in serum
Presence of disease
Organs involved
Aetiology /nature of disease: differential diagnosis
Extent of disease-more damaged cells-more leaked enzymes in
blood
Time course of disease

4. SERUM ENZYMES IN HEART DISEASES
1) CK(CPK)
2) CK-MB
3) Troponin-I/T
4) LDH
5) AST
6) Others

5.  Not enzymes
 Now accepted as reliable markers for
myocardial infarction
 3 subunits:-
1) Troponin T(TnT): Tropomyosin binding
elements
2) Troponin I(TnI): Actinomyosin ATPase
inhibitory elements
3)Troponin C(TnC): Calcium binding

6.  Cardiac isoform of CTnT & CTnI:-
95% located in myofibrils &
5% cytoplasmic
 TnT:- ↑ within 6 hrs of MI & remains ↑ up to 7-14
days.
 TnI:- released into the blood within 4 hrs after the
onset of symptoms of myocardial ischemia; peaks
at 14-24 hrs & remains ↑ for 3-5 days post-
infarction.
Note:- cardiac troponin ↑ at lower conc. than the 99th percentile
value used for MI but still have a risk of having an adverse cardiac
event.
Troponin-I:- 1 – 10 µg/L

7. 1) H-FABP:-
 Heart-type fatty acid binding protein
 Kinetically similar to myoglobin but more
specific to cardiac tissue which contains a
greater percentage of this protein than skeletal
muscle
 May also have role in prediction- prognosis in
patients with NSTEMI
 Current studies ongoing to further evaluate its
utility

8. 2) Brain Natriuretic Peptide(BNP):-
 Natriuretic peptide family consists of 3
peptides:-
a) atrial natriuretic peptide(ANP)
b) brain natriuretic peptide(BNP)
c) C-type natriuretic peptide(CNP)
 ANP:-produced in cardiac atria.

9.  BNP:-
 present in human brain but more in cardiac
ventricles.
 pro-BNP- 108A.As
 High plasma conc. of ANP & BNP :- CHF
 ↑ BNP- COPD
 pro-BNP:- best marker of ventricular dysfunction

10. Myeloperoxidase
• MPO is an enzyme that aids white blood cells in
destroying bacteria and viral particles
• MPO catalyzes the conversion of hydrogen
peroxide and chloride ions (Cl-) into hypochlorous
acid
• Hypochlorous acid is 50 times more potent in
microbial killing than hydrogen peroxide
• MPO is released in response to infection and
inflammation
• EPIC Norfolk Study showed its predictive value
for future cardiovascular disease events in
asymptomatic adults.

11. • MPO leads to oxidized LDL cholesterol
– Oxidized LDL is phagocytosed by macrophages
producing foam cells*
• MPO leads to the consumption of nitric oxide
– Vasoconstriction and endothelial dysfunction
• MPO can cause endothelial denuding and
superficial platelet aggregation
• MPO indicates activated immune cells
– Activated immune cells and inflammation lead to
unstable plaque*
• Inflammatory plaque is inherently less stable
– Thin fibrous cap/fissured/denuded
Brennan, NEJM 2003
*Hansson, NEJM 2005

12.  Chronic inflammation also is an important
component in the development & progression of
atherosclerosis.
 Numerous epidemiological studies have
demonstrated that ↑ serum CRP conc. are +vely
associated with a risk of future CHD events when
using an hsCRP assay.
 Synthesis- LIVER

13.  Single hs-CRP measurement is a stong predictor
of:-
a) MI
b) Stroke
c) Peripheral vascular disease
d) Sudden cardiac death:- individuals without a
history of heart disease.
 Direct comparison of traditional and novel
biochemical markers of CHD risk, hsCRP is the
strongest predictor of future coronary events.

15. Stefan Blankenberg, MD; Renate Schnabel, MD; Edith Lubos, MD, et al., Myeloperoxidase Early Indicator of Acute Coronary Syndrome and
Predictor of Future Cardiovascular Events 2005

16. 1) ALT
2) ALP
3) NTP
4) GGT

18.  Very much elevated in muscular dystrophies(500-1500 IU/L).
 Female carriers of X-linked muscular dystrophy (heterozygous)
Raised values:-
Secondary muscle disease
Hypothyroidism
Crush injury
Fracture &
Cerebrovascular accidents.
Actual values depends on:-
Severity of the disease &
Mass of diseased muscle.

19. 2) AST :- not used now-a-days.
3) Aldolase:-
 glycolytic enzyme
 until recent years enzyme of choice
 more sensitive than AST
Sites:- Liver, skeletal muscle & brain.
Also found in neoplastic tissues.

20.  Drastically elevated in muscle damages
eg- progressive muscular dystrophy
poliomyelitis
myasthenia gravis
multiple sclerosis.
Also ↑ in liver diseases, myocardial
infarction & Leukemia.

21.  Non-specific enzymes
 hydrolyses aliphatic, aromatic or heterocyclic
compounds.
 optimum PH:- betn 9-10.
 activated by magnesium & manganese.
 Zn is a constituent ion of ALP.

22.  Produced by osteoblasts of bone
 associated with calcification process.
 localised in cell membranes (ecto-enzyme)
 Also associated with transport mechanisms in
liver, kidney & intestinal mucosa.

23. i) α1 – ALP:-
 Synthesized by epithelial
cells of biliary canaliculi.
 about 10% of total activity
 ↑ in obstructive jaundice.
ii) α2 – ALP:- heat labile
 Stable at 56
o
C
 Produced by hepatic cells
 About 25% of total ALP

24. iii) α2 – ALP:- heat stable
 not be destroyed at 65o
C
 inhibited by Phenylalanine
 placental origin:- found in blood in normal
pregnancy.
 carcinoplacental iso-enzyme:- carcinoma of
lungs, liver & gut.
 1% of ALP

25. iv) pre-β ALP:- heat labile
 origin- bone
 50% of normal ALP
 ↑ in bone diseases.
 marker of bone disease
v) γ- ALP:-
 origin- intestinal cells
 inhibited by phenylalanine
 ↑ in ulcerative colitis.
 10% of ALP
vi) Leukocyte- ALP:-
 ↑ in LYMPHOMA
↓ in CML

26. C) Drastically high levels:- 10-25 times of upper limit
 bone diseases
Osteoblastic activity is enhanced such as paget’s disease,
rickets, osteomalacia, osteoblastoma, metastatic carcinoma of
bones & hyperparathyroidism.
A) Moderate ↑:- 2-3 times
 Hepatic diseases such as infective hepatitis,
alcoholic hepatitis or hepatocellular carcinoma.
B) Very high:- 10-12 times
 Extrahepatic obstruction (obs. Jaundice)
 Intrahepatic cholestasis ( infective hepatitis

27. 1) Prostate specific antigen (PSA)
2) Acid phosphatase (ACP)

28. Produced from epithelium of prostate gland.
 Normally secreted in to seminal fluid.
 liquefaction of seminal coagulum.
 serine protease & 32 Kd glycoprotein.
 Blood- bound to α2-macro-globulin & α1 – antitrypsin.
very specific for prostate activity
 Values above 10µg/L is indicates prostate cancer.

29.  an important tumor marker
Secreted by prostate cells, RBC, Platelets & WBC.
Hydrolyses phosphoric acid ester at PH betn 4-6.
 ACP of prostate is inhibited by L-tartrate i.e tartrate labile (1 U/L)

30.  ↑ ed in prostate cancer & highly elevated in bone metastasis of prostate
cancer.
 Marked ↑ in:-
○ Gaucher’s disease,
○ thrombocytosis,
○ chronic granulocytic leukaemia,
○ myeloproliferative disorders etc.
Occasional rise in:-
○ paget’s disease,
○ hyperparathyroidism &
○ osteolytic metastasis from breast & other carcinomas.

31. SERUM ENZYMES IN GI-TRACT DISEASES
1) Serum amylase
2) serum lipase

32.  Splits Starch to maltose.
 activated by Ca2+ & Cl- ions.
 produced by:- Pancreas & salivary glands.
– S1,S2,S3; P1,P2,P3

33.  Investigation of choice
 ↑ 1000 times more
 peak values: 5-12 hrs (after onset of disease)
 return to normal within 2-4 days.

34.  Chronic pancreatitis.
 mumps (parotitis)
 Obstruction of pancreatic duct.
 Peptic ulcer
 intestinal obstruction.
 Urine amylase:- <375 IU/L
 ↑ in acute pancreatitis.
 ↑ on 1st day & remain to be ↑ for 7-10 days.

35. TG ------› MAG + FFA
 Present:- pancreatic secretion.

36. Significance of lipase:-
 highly ↑ blood levels.
 persists for 7-14 days.
 lipase remains ↑ longer than amylase.
 not ↑ in mumps.
 Carcinoma of pancreas
 biliary diseases
 peptic ulcers.

37. Distribution: liver, bowels, NS, pancreas
Increased in: obstructive type of hepatobiliary
diseases
Normal values :- 2-15 IU/L

38. Gamma Glutamyl Transferase (GGT):-
Source:
major- Liver & bile ducts.
others- pancreas, kidney &
prostate gland.
Clinical Significance:-
 obstructive jaundice
 Hepatitis
 Alcoholic cirrhosis
 Sensitive indicator:-
Alcoholic cirrhosis

39. 2 types:-
1) True cholineesterase :-
(acetylcholine hydrolase &
acetyl-cholineesterase)
Present:- nerve tissue & RBC.
Function:- hydrolysis of acetylcholine at the synapses &
neuromuscular junction.
2) Pseudocholinesterase :-
(acetylcholine acyl-hydrolase &
Cholinesterase)
Present:- liver, heart muscle, intestine & sera.
Function:- not known

40. Clinical Significance:-
 Liver function test
 imp. Indicator of insecticide poisoning.
 ↓ in:-
Uremia, shock, anemia, cancer,
tuberculosis & malnutrition.
• Degrades succinylcholine, a muscle relaxant given during general
anesthesia in surgery.
• Some people are deficient in plasma cholinesterase (congenital
inherited recessive disease), so the normal dose of succinyl-choline
would kill them
Therefore, a determination of plasma cholinesterase is made
prior to major surgery.

41. Distribution: liver, kidney, bowels.
Increased in: hepatobiliary diseases
(obstruction, hepatic metastases).

42. ORNITHINE CARBAMYL TRASFERASE(OCT)
Ditribution: only liver (hepatospecific).
Increased in: liver diseases (hepatitis, cirrhosis, hepatic
metastases).

43. Enzymes Therapeutic applications
1) Asparaginase Acute lymphoblastic
leukemia
2) Streptokinase To lyse intravascular clot
3) Urokinase do
4) streptodornase DNAse; applied locally
5) Pancreatin (trypsin &
lipase)
Pancreatic insufficiency; oral
administration
6) Papain Anti-inflammatory
7) α1 - antitrypsin AAT deficiency; emphysema

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And no one can deny it
Are sunshine, water, rest, and air
Exercise and diet.
These six will gladly you attend
If only you are willing
Your mind they'll ease
Your will they'll mend
And charge you not a shilling.

45. ‘’Centre for The Cureness’’