CLINICAL ENZYMOLOGY
PLASMA ENZYMES
Measurements of the activity of enzymes in plasma
are of value in the diagnosis and
management of a wide variety of
diseases. Most enzymes measured in plasma are primarily intracellular, being
released into the blood when there is damage to cell membranes, but many
enzymes, for example renin, complement factors and coagulation factors, are
actively secreted into the blood, where they fulfil their physiological
functions.
Small amounts of intracellular enzymes are present in
the blood as a result of normal cell turnover. When damage to cells occurs,
increased amounts of enzymes will be released and their concentrations in the
blood will rise. However, such increases are not always due to tissue damage.
Other possible causes include:
·
increased
cell turnover
·
cellular
proliferation (e.g. neoplasia)
·
increased
enzyme synthesis (enzyme induction)
·
obstruction
to secretion
·
decreased
clearance.
Little is known about the mechanisms by which enzymes
are removed from the circulation. Small molecules, such as amylase, are
filtered by the glomeruli but most enzymes are probably removed by
reticuloendothelial cells. Plasma amylase activity rises in acute renal failure
but, in general, changes in clearance rates are not known to be important as
causes of changes in plasma enzyme levels.
CLINICAL ENZYMOLOGY
Plasma contains many functional enzymes, which a
actively secreted into plasma. For example, enzymes blood coagulation. On the
other hand, there are a few non functional
enzymes in plasma, which are coming out from cells of various
tissues due to normal wear and tear. Their normal levels in blood are very low;
but are drastically increased during cell death (necrosis) or disease.
Therefore assays of these enzymes are very useful in diagnosis diseases.
Enzyme Units
Enzyme assays usually depend on the measurement the
catalytic activity of the enzyme, rather than the concentration of the enzyme
protein itself. Since each enzyme molecule can catalyze the reaction of many
molecules of substrate, measurement of activity provides great sensitivity. It
is, however, important that the conditions of the assay are optimized and
standardized to give reliable and reproducible results. Reference ranges for
plasma enzymes are dependent on assay conditions, for example temperature, and
may also be subject to physiological influences. It is thus important to be
aware of both the reference range for the laboratory providing the assay and
the physiological circumstances when interpreting the results of enzyme assays.
One international unit is the
amount of enzyme that will convert one micromole of substrate per minute per litre
of sample and is abbreviated as U/L. The SI Unit (System Internationale)
expression is more scientific, where or Katal
(catalytic activity) is defined as the number of mole of substrate
transformed per second per litre of sample. Katal is abbreviated as kat or k
(60 U = 1 μkat and 1 nk = 0.06 U).
Disadvantages of enzyme assays
A major disadvantage in the use of enzymes for the
diagnosis of tissue damage is their lack of specificity to a particular tissue
or cell type. Many enzymes are common to more than one tissue, with the result
that an increase in the plasma activity of a particular enzyme could reflect
damage to any one of these tissues. This problem may be obviated to some extent
in two ways:
first, different tissues may contain (and thus release
when they are damaged) two or more enzymes in different proportions; thus
alanine and aspartate aminotransferases are both present in cardiac and
skeletal muscle and hepatocytes, but there is only a very little alanine
aminotransferase in either type of muscle;
second, some enzymes exist in different forms
(isoforms), colloquially termed isoenzymes (although, strictly, the term
'isoenzyme' refers only to a genetically determined isoform). Individual
isoforms are often characteristic of a particular tissue: although they may
have similar catalytic activities, they often differ in some other measurable
property, such as heat stability or sensitivity to inhibitors.
After a single insult to a tissue, the activity of
intracellular enzymes in the plasma rises as they are released from the damaged
cells, and then falls as the enzymes are cleared. It is thus important to
consider the time at which the blood sample is taken in relation to the insult.
If taken too soon, there may have been insufficient time for the enzyme to
reach the blood- stream and if too late, it may have been completely cleared.
As with all diagnostic techniques, data acquired from measurements of enzymes
in plasma must always be assessed in the light of whatever clinical and other
information is available, and their limitations borne in mind.
LACTATE
DEHYDROGENASE (LDH) (LD)
The total LDH is generally tested by reaction of the
serum sample with pyruvate and NADH2. LDH will convert pyruvate to lactate,
and in turn NADH is use up by the reaction.
Normal value of LDH in serum is 100-200 U/L. Values the upper range are generally seen in
children. Strenuous exercise will slightly increase the value. LDH level is 100
times more inside the RBC than in plasma, and therefore minor amount of
hemolysis will result in a false-positive test.
LDH
and Heart Attack
In myocardial infarction, total LDH activity is
increased, while H4 iso-enzyme is increased 5-10 times more.
Differential diagnosis: Increase in total LDH level is seen in hemolytic anemias, hepatocellular damage,
muscular dystrophy, carcinomas, leukemias, and any condition which causes
necrosis of body cells. Since total LDH is increased in many conditions, the study
of isozymes of LDH is of great importance.
Isoenzymes of LDH
LDH enzyme is a tetramer with four subunits. But the
subunit may be either H (heart) or M (muscle) polypeptide chains. These two are
the products of two different genes.
Although both of them have the same molecular weight
(32 kD), there are minor amino acid variations. So five combinations of H and M
chains are possible; H4, H3M, H2M2,
M3H and M4 varieties, forming five iso-enzymes. All these
five forms are seen in all persons. M4 form is seen in skeletal
muscles; it is not inhibited by pyruvate. But H4 form is seen in
heart and is inhibited by pyruvate. Normally LDH-2 (H3M1)
concentration in blood is greater than LDH-1 (H4); but this pattern is reversed
in myocardial infarction; this is called flipped pattern. The
iso-enzymes are usual ly separated by cellulose acetate electrophoresis at
pH 8.6. They are then identified by adding the reactants finally producing a
colour reaction. . Lactate dehydrogenase isoenzymes (as percentage of total):
LDH1
14-26 %
LDH2
29-39 %
LDH3
20-26 %
LDH4
8-16%
LDH5
6-16 %
CREATINE KINASE(CK)
It is used for the
reaction shown in Figure:
Creatine → Creatine phosphate
It was called as creatine
phosphokinase in old literature.
Normal
serum value for CK is 15-100 U/L for males and 10-80 U/L for
females.
CK
and Heart Attack CK
value in serum is increased in myocardial
infarction. The CK level starts to rise within three hours of infarction. Therefore, CK estimation
is very useful to detect early cases, where ECG changes may be ambiguous. The
CK level is not increased in hemolysis or in congestive cardiac failure; and
therefore CK has an advantage over LDH.
CK
and Muscle Diseases he
level of CK in serum is very much elevated in muscular dystrophies (500 -1500
IU/L). The level is very high in the early phases of the disease. In such
patients a fall in CK level is indicative of deteriorating condition, because
by that time, all muscle mass is destroyed. In female carriers of this X-linked
disease (genotypically heterozygous), CK is seen to be moderately raised. CK
level is highly elevated in crush injury, fracture and acute cerebrovascular
accidents. Estimation of total CK is
employed in muscular dystrophies and MB iso-enzyme is estimated in myocardial
infarction.
Iso-enzymes
of CK CK is a
dimer; each subunit has a molecular weight of 40,000. The subunits are called B
for brain and M for muscle. They are products of loci in chromosomes 14 and 19
respectively. Therefore three iso-enzymes are seen in circulation. Normally CK2
is only 5% of the total activity. Even doubling the value in CK2
(MB) iso-enzyme may not be detected, if total value of CK alone is estimated. Hence the detection
of MB-iso-enzyme is important in myocardial infarction. CK-MB
< 6 % of total CK in normal conditions.
The above three
iso-enzymes are cytosolic. A fourth variety, called CK-mt is located in mitochondria
and constitutes about 15% of total CK activity. Its gene is located in
chromosome 15. CK1 may be complexed with immunoglobulin; and then termed
macroCK. CK1-lgG causes false-positive diagnosis of myocardial
infarction because it has an electrophoretic mobility close to CK2.
For quantitating MB iso-enzyme, anti-MM
antiserum is added to the patient's serum. This will precipitate MM iso-enzyme.
The supernatant serum is used for the CK estimation. Here it is assumed that BB
isoenzyme is negligible in quantity, which is correct if there is no brain
disease. CK iso-enzymes can also be identified by electrophoresis.
TRANSFERASES
AST present in cytosol and mitochondria
ALT located in cytosol of liver
In the liver, the concentration of ALT per unit
weight of the tissue is more than AST.
These enzymes are more important in assessing
and monitoring the degree of liver cell
inflammation and necrosis.
The highest activities of ALT are found in
hepatocytes and muscle cells.
Again the hepatocytes have very high activity of
ALT.
Therefore elevations in serum ALT are considered
to be relatively specific for liver disease.
AST may be elevated in other forms of tissue
damage, such as myocardial infarction,
muscle necrosis and renal disorders.
In liver disease, the ALT level is increased
markedly compared to AST.
In acute viral hepatitis there is a 100-1000
times increase in both ALT and AST but ALT
level is increased more than that of AST
ASPARTATE AMINO TRANSFERASE (AST)
It is also called as serum
glutamate-oxaloacetate transaminase (SGOT). AST needs pyridoxal phosphate as
co-enzyme. AST is estimated by taking aspartate, α-ketoglutarate, pyridoxal phosphate
(vitamin B6) and patient' serum as the source of AST. The oxaloacetate
formed may be allowed to react with dinitrophenyl hydrazine to produce a colour
which is estimated colorimetrically at 520 nm.
Normal serum level of AST is 8-40 U/L or (0,1-0,45 mmol/(hour´L))
It is significantly elevated in myocardial
infarction. It if moderately elevated in liver diseases. However, a marked
increase in AST may be seen in primary hepatoma. AST has two iso-enzymes;
cytoplasmic and mitochondrial. In mile degree of tissue injury, cytoplasmic
form is seen in serum. Mitochondrial type is seen in severe injury.
Marked increase (10 to
100 times the upper adult reference limit):
Circulatory
failure with 'shock' and hypoxia:
Myocardial
infarction
Acute
viral or toxic hepatitis.
Moderate increase
Cirrhosis
(may be normal, but may rise to twice the upper adult reference limit):
Infectious
mononucleosis (due to liver involvement):
Cholestatic
jaundice (up to 10 times the upper adult reference limit):
Malignant
infiltration of the liver (may be normal, but may rise to twice the upper
reference
limit):
Skeletal
muscle disease:
After
trauma or surgery (especially after cardiac surgery):
Severe
haernolytic episodes (of erythrocyte origin).
ALANINE AMINO TRANSFERASE (ALT)
It is also called as serum
glutamate-pyruvate transaminase (SGPT). ALT needs pyridoxal phosphate as
co-enzyme.
Normal
serum level of ALT is 5-30 U/L
or (0,1-0,68 mmol/(hour´L))
Very high values (100 to 1000 U/L)
are seen in acute hepatitis, either toxic or viral in origin. Both ALT and AST
are increased in liver diseases, but ALT >AST. Moderate increase (25 to 100
U/L) may be seen in chronic liver disease such as cirrhosis, and malignancy in
liver. A sudden fall in ALT level in cases of hepatitis is a very bad
prognostic sign.
Ritis
coefficient (AST/ALT) in normal
conditions is 1,33±0,42.
Marked
increase (10 to 100 times the upper limit of the adult reference
range circulatory failure with 'shock' and hypoxia:
Acute viral or toxic hepatitis.
Moderate
increase:
Cirrhosis (may be normal or up to twice the
upper adult reference limit): infectious
mononucleosis (due to liver involvement):
Liver congestion secondary to congestive cardiac
failure:
cholestatic jaundice (up to 10 times the upper
reference limit in adults); surgery or
extensive trauma and skeletal muscle disease
(much less affected than AST)
Alkaline phosphatase (ALP)
It is a non- specific enzyme which
hydrolyses aliphatic, aromatic or heterocyclic compounds. The pH optimum for the
enzyme reaction is between 9 and 10. It is prodused by osteoblasts of bone, and
localized in cell memmbranes (ecto-enzyme).
Normal serum level of ALP is 40-125 U/L or 0,5-1,3 mmol/(hour´ L).
In children the upper level of
normal value may be more, becouse of the increased osteoblastic activity. Mild
increase is noticed during pregnancy, due to production of placental isoenzyme.
Moderate (2-3 times) increase in ALP
level is seen in hepatic diseases such as hepatitis, alcoholic hepatosis or
hepatocellular carcinoma. Very high levels of ALP (10-12 times of upper limit)
may be noticed in extrahepatic obstructions or cholestasis. ALP is produced by
epithelial cells of biliary canaliculi and obstruction of bile with consequent
irritation of epithelial cells leads to secretion of ALP into serum.
Drastically high levels of ALP
(10-25 times of upper limit) are also seen in bone diseases where osteoblastic
activity is enhanced such as Paget's disease, rickets, osteomalacia,
osteoblastoma, metastatic carcinoma of bone and hyperparathyroidism (Paget's
disease or osteitis deformans was described in 1877 by Sir James Paget).
Iso-enzymes of Alkaline Phosphatase
1.
α-1
ALP moves in α -1 position, it is synthesised by epithelial cells of
biliary canaliculi. It is about 10% of total activity and is increased in
obstructive jaundice and to some extent in metastatic carcinoma of liver.
2.
α
-2 heat labile ALP is stable at
3.
α
-2 heat stable ALP will not be destroyed at
4.
Pre-ß
ALP is of bone origin and elevated levels are seen in bone diseases. This is
the most heat labile (destroyed at
5.
γ-ALP
is inhibited by phenylalanine and originates from intestinal cells. It is
increased in ulcerative colitis. About 10% of plasma ALP are of intestinal
variety.
6.
The
leucocyte alkaline phosphatase (LAP) is significantly decreased in chronic
myeloid leukemia. It is increased in lymphomas.
ALP has different
isoforms. Although ALP is a monomer, depending on the number of sialic acid
residues, the charged groups differ. Such different forms are detected in agar
gel electrophoresis.
NUCLEOTIDE
PHOSPHATASE (NTP)
It is also known as 5' nucleotidase. This enzyme
hydrolyses 5' nucleotides to corresponding nucleosides at an optimum pH of 7.5.
It is a marker enzyme for plasma membranes and is seen as an ecto-enzyme
(enzyme present on the cell membrane).
Usually, AMP is used
as substrate, which is hydrolysed to adenosine and inorganic phosphate. The
latter reacts with ammonium molybdate to produce the yellow ammonium
phosphomolybdate, which is estimated colorimetrically. However, ALP will also
catalyse the same reaction. Serum samples contain both ALP and NTP. These are
distinguished by Nickel ions which inhibit NTP but not ALP.
Normal NTP level in serum is 2-10 U/L. It is moderately increased in hepatitis and highly elevated
in biliary obstruction. Unlike ALP, the level is unrelated with osteoblastic
activity and therefore is unaffected by bone diseases.
GAMMA
GLUTAMYL TRANSFERASE (GGT)
The old name was gamma glutamyl
transpeptidase. It can transfer γ-glutamyl residues to substrate. In the
body it is used in the synthesis of glutathione. GGT has 11 iso-enzymes. It is
seen in liver, kidney, pancreas, intestinal cells and prostate gland.
Normal serum value of GGT is 6-45
U/L in male and 5-30 U/L in female. It is slightly
higher in normal males, due to the presence of prostate gland. This value is
moderately increased in infective hepatitis and prostate cancers. The GGT level
is highly elevated in alcoholism, obstructive jaundice and neoplasm's of liver.
GGT-2 is positive for 90% of hepatocellular carcinomas. It is not elevated in
cardiac or skeletal diseases.
GGT is a microsomal
enzyme. Its activity is induced by alcohol, phenobarbitone and rifampicin. GGT
is clinically important because of its sensitivity to detect alcohol abuse. GGT
is increased in alcoholics even when other liver function tests are within
normal limits. GGT level is rapidly decreased within a few days when the person
stops to take alcohol. Increase in GGT level is generally proportional to the amount
of alcohol intake.
ACID PHOSPHATASE (ACP)
It hydrolyses phosphoric acid ester at pH between 4
and 6. Methods for assay are the same as described for ALP; but the pH of the
medium is kept at 5 to 5.4.
Normal
serum value for ACP is 2.5-12 U/L or 0,025-0,12
mmol/(hour´ L).
ACP is secreted by prostate cells, RBC,
platelets and WBC. Isoenzymes of ACP are described. Erythrocyte ACP gene is
located in chromosome 2; osteoclast ACP gene is on chromosome 19; lysosomal
gene is on 11 and prostate ACP gene is on 13. The prostate iso-enzyme is
inactivated by tartaric acid. Cupric ions inhibit erythrocyte ACP. Normal level
of tartrate labile fraction of ACP is 1 U/L.
ACP total value is
increased in prostate cancer and highly elevated in bone metastasis of prostate
cancer. In these conditions, the tartrate labile iso-enzyme is elevated. This
assay is very helpful in follow up of treatment of prostate cancers. ACP is
therefore an important tumour marker.
Since
blood cells contain excess quantity of ACP, must be taken to prevent hemolysis
while taking blood from the patient. Prostate massage may also increase to
value. So blood may be collected for ACP estimation before per rectal
examination of patient. ACP is present in high concentration in semen, a
finding which is used in forensic medicine in investigation of rape.
The main indications for estimation are to help
diagnose prostatic carcinoma and to monitor
its treatment. The estimation is gradually being replaced by the
measurement of plasma prostate specific antigen (PSA) a protein derived from
the prostate. This test is more specific
and sensitive for diagnosis and monitoring treatment. However, it may be
raised in similar circumstances to those
affecting prostatic ACP and is more expensive to estimate. ACP is more
useful for monitoring the treatment of a known case of
disseminated prostatic carcinoma than for making the diagnosis.
PROSTATE SPECIFIC ANTIGEN (PSA)
It is produced from the secretory
epithelium of prostal gland. It is normally secreted into seminal fluid, where
it is necessary for the liquefaction of seminal coagulum. It is a serine
protease, and is a 32 kD glycoprotein; encoded in chromosome number
Normal
value is 1 -5 µg/L. It is very specific for prostate activity.
Values between 4-10 µg/L is seen in
benign prostate enlargement; but values above 10 µg/L is indicative of prostate
cancer.
CHOLINESTERASE (ChE)
Acetyl cholinesterase
or true ChE or Type 1 ChE can act mainly on acetyl choline. It is present in
nerve endings and in RBCs. About 25 allelic forms are reported. Normal serum
range is 2-12 U/ml. Newly formed RBC will contain good quantity of ChE which is
slowly reduced according to the age of the cell. Therefore, ChE level in RBCs
will be proportional to the reticulocyte count. Organophosphorus insecticides
(Parathione) irreversibly inhibit ChE in RBCs. Measurement of ChE level in RBCs
is useful to determine the amount of exposure in persons working with these
insecticides.
Pseudocholinesterase
or type II ChE is non-specific and can hydrolyse acyl esters. It is produced
mainly by liver cells. Normal serum level is 8-18 U/ml. Succinyl choline is a widely used as muscle
relaxant. It is a structural analogue of
ACh, and so competitively fix on post-synaptic receptors of ACh. Succinyl
choline is hydrolysed by the liver ChE within 2-4 minutes. But in
certain persons the ChE activity may be absent; this is a genetically transmitted
condition. In such individuals when succinyl choline is given
during surgery, it may take hours to get the drug metabolised. Very prolonged
scoline apnoea may result in 'nightmare of anaesthetist'. The
pseudocholinesterase level in serum is reduced in viral hepatitis, cirrhosis,
hepatocellular carcinoma, metastatic cancer of liver and in malnutrition.
Causes of decreased plasma
cholinesterase activity
•
Hepatic parenchymal disease (reduced synthesis).
•
Ingestion or absorption through the skin, of such anticholinesterases as
organophosphates.
•
Inherited abnormal cholinesterase variants, with low biological activity.
Causes of increased plasma
cholinesterase activity
a.
Recovery from liver damage (actively growing hepatocytes)
b.
Nephrotic syndrome
GLUCOSE-6-PHOSPHATE DEHYDROGENASE
GPD is a dimer with identical subunits. This is an
important enzyme in the hexose monophosphate shunt pathway of glucose. It is mainly used for production of NADPH . It has a special role
in the RBC metabolism. Due to the presence of oxygen, hydrogen peroxide is continuously formed inside the RBC. Peroxide
will destroy biomembranes, and RBCs
are lysed.
Normal value of GPD in RBC is
125-250 U/1012 cells. Nearly 400 variants
(isoforms) of GPD are described.
AMYLASE
This splits starch to maltose. It is activated by
calcium, chloride and fluoride ions. There are 18 phenotypes. It is produced by
pancreas and salivary glands; they are products of different genes located in
chromosome 1.
Normal
serum value is 50-120 U/L, (12-32
g/(hour×
L)).
The value is increased about 1000
times in acute pancreatitis which is a life-threatening condition. The peak
values are seen between 5-12 hours after the onset of disease and returns to
normal levels within 2-4 days after the acute phase has subsided. Moderate
increase in serum levels are seen in chronic pancreatitis, mumps (parotitis),
obstruction of pancreatic duct and in renal disease. In the last condition, the
enzyme is not excreted through urine properly and hence serum value is raised. Normal
urine value is 20-160 g/(hour× L) or (less than 375 U/L). It is increased in acute pancreatitis. It is
increased on the
LIPASE
It will hydrolyse triglyceride to
β-monoglyceride and fatty acid. Molecular weight is 54,000. The gene is in
chromosome 10. The enzyme is present in pancreatic secretion. Normal serum range is 0.2-1.5 U/L. It is highly elevated in acute pancreatitis and this
persists for 7-14 days. Thus, lipase remains elevated longer than amylase.
Moreover, lipase is not increased in mumps. Therefore, lipase estimation has
advantage over amylase. It is moderately increased in carcinoma of pancreas,
biliary diseases and perforating peptic ulcers.
Aldolase
(ALD)
It is a tetrameric enzyme with A and B subunits; so
there are 5 iso-enzymes. It is a glycolytic enzyme. Normal range of serum is 1.5-7 U/L.
It is drastically elevated in muscle damages such as progressive muscular dystrophy,
poliomyelitis, myasthenia gravis and multiple sclerosis. It is a very sensitive
early index in muscle wasting diseases.
Enolase
It is a glycolytic enzyme. Neuron-specific enolase
(NSE) is an iso-enzyme seen in neural tissues and Apudomas. NSE is a tumour
marker for cancers associated with neuro-endocrine origin, small cell lung
cancer, neuroblastoma, pheochromocytoma, medullary carcinoma of thyroid, etc.
It is measured by RIA or ELISA. Upper limit of NSE is 12 μg/ml.
Enzymes
in Malignancy
Plasma
total enzyme activities may be raised or an abnormal isoenzyme detected, in
several neoplastic disorders.
•
Serum prostatic (tartrate-labile) acid phosphatase activity rises in some cases
of malignancy of the prostate gland.
•
Any malignancy may be associated with a non-specific increase in plasma LD1
(HBD) and occasionally, transaminase activity.
•
Plasma transaminase and alkaline phosphatase estimations may be of value to
monitor treatment of malignant disease. Raised levels may indicate secondary
deposits in liver or of alkaline phosphatase, in bone. Liver deposits may also
cause an increase in plasma LD or GGT.
•
Tumors occasionally produce a number of enzymes, such as the 'Regan' ALP isoenzyme.'
LD
(HBD) or CK-BB. assays of which may be used as an aid to diagnosis or for
monitoring treatment.
Other
Clinical correlations
1. Niemann-Pick disease: Acid
Sphingomyelinase Deficiency
·
Sphingomyelin, a ubiquitous component of cell membranes, especially neuronal
membranes, is normally degraded within lysosomes by the enzyme
sphingomyelinase.
·
In patients with Niemann-Pick disease, inherited deficiency of this enzyme
causes spingomyelin to accumulate in lysosomes of the brain, bone marrow, and
other organs.
·
Enlargement of the lysosomes interferes with their normal function, leading to
cell death and consequent neuropathy.
·
Symptoms include failure to thrive and death in early childhood as well as learning
disorders in those who survive the postnatal period.
2. Homocysteinuria: Cystathionine
β-synthase Deficiency
1.
Cystathionine β-synthase catalyzes conversion of homocysteine to
cystathionine, a critical precursor of cysteine.
2.
Deficiency of this enzyme leads to the most common form of homocystinuria, a
pediatric disorder characterized by accumulation of homocysteine and reduced
activity of several sulfotransferase reactions that require this compound or
its derivatives as substrate.
3.
Accumulation of homocysteine and reduced transsulfation of various compounds
leads to abnormalities in connective tissue structures that cause altered blood
vessel wall structure, loss of skeletal bone density (osteoporosis), dislocated
optic lens (ectopia lentis), and increased risk of blood clots.
3. Enzyme Replacement Therapy for
Inborn Errors of Metabolism
·
Lysosomal enzyme deficiencies, which frequently result in disease due to
accumulation of the substrate for the missing enzyme, are suitable targets for
enzyme replacement therapy (ERT).
·
In ERT, intravenously administered enzymes are taken up directly by the
affected cells through a receptor-mediated mechanism.
·
ERT provides temporary relief of symptoms but must be given repeatedly and is
not a permanent cure.
Summary
1.
Enzyme concentrations are high in cells. Natural decay of these cells releases
enzymes into the plasma. Plasma activities are usually low but measurable.
2.
Plasma enzyme assays are most useful in the detection of raised levels due to
cell damage.
3.
Assays of selected enzymes may help to identify the damaged tissues and
isoenzyme studies may increase the specificity. In general, knowledge of the
patterns of enzyme changes, together with the clinical and other findings, are
needed if a useful interpretation is to be made.
4.
Non-specific causes of raised enzyme activities include peripheral circulatory
insufficiency, trauma, malignancy and surgery.
5.
Artefactual increases may occur in haemolysed samples.
6.
Enzyme estimations may be of value in the diagnosis and monitoring of:
a.
• Myocardial infarction (CK. LD and its isoenzymes and sometimes AST);
b.
• Liver disease (transaminases. ALP and sometimes GGT):
c.
• Bone disease (ALP):
d.
• Prosratic carcinoma (tartrate-labile ACP);
e.
• Acute pancreatitis (α-amylase):
f.
• Muscle disorders (CK)