Cholinesterase refers to two enzymes, acetylcholinesterase and pseudocholinesterase, that play crucial roles in the nervous system and can be affected by pesticide exposure. Measurement and monitoring of cholinesterase levels are essential for assessing exposure risks, particularly for individuals working with organophosphate pesticides, and guidelines recommend baseline readings and regular testing for effective oversight. Variations in cholinesterase levels necessitate individual baseline assessments to accurately gauge any harmful changes and implement necessary actions based on defined thresholds.

1. CHOLINESTERASE
 INTRODUCTION
 CLINICAL UTILITY
 METHOD OF MEASUREMENT
By Dr. Kamal Modi
Biochemistry Dept.

2. INTRODUCTION
 Cholinesterase (ChE) is the general term for two enzymes
in the human body: acetylcholinesterase (AChE) and
Pseudocholinesterase (PChE).
Acetylcholinesterase Pseudocholinesterase
Found in erythrocytes, lungs,
spleen, nerve endings & gray matter
of brain
Found in liver, pancreas, heart,
white matter of brain, serum
Responsible for hydrolysis of
acetylcholine at nerve endings to
mediate impulse transmission across
synapse
Deactivation of octanoyl ghrelin,
hormone that stimulates feeding &
promotes weight gain.

3.  In the nervous system AChE acts to “turn off” the signal delivered
by cholinergic nerves by removing the neurotransmitter
acytelcholine.
 Thus if AChE is inhibited, acetylcholine builds up causing over-
stimulation of cholinergic systems.
 This over-stimulation of muscles, glands and other nerves is what
causes most of the symptoms associated with overexposure to
cholinesterase-inhibiting pesticides.
 OP and N-methyl-carbamates inhibit cholinesterase by binding to
the serine hydroxyl group on acetylcholinesterase Which is active
site of the enzyme.
 OPs may bind irreversibly with the enzyme while the N-methyl-
carbamate bond is reversible.

4. Genetic basic
• Most common allelic forms of genes that control synthesis
of cholinesterase are Eu, Ea, Ef, Es which describes as
below:
Eu Normal phenotype
Ea Weakly active towards most substrate for CHE
Incresed resistance to inhibition of enzyme activity
by dibucaine.
Ef Increased resistance to flouride inhibition
Es Absence of enzyme or presence of protein with
minimal or no catalytic activity

5. Clinical significance
As liver function test
As an indicator of possible insecticide
poisoning
For detection of patients with atypical
forms of enzyme who are at risk for
prolonged responses to certain muscle
relaxants

6. Serum
Cholinesterase
RBC
Cholinesterase
Labile more Less
Inactivation faster Slow
Regeneration faster Slow
Accuracy less More
Indication For acute
cases
For chronic
cases

7.  Blood test measurements of both AChE and
PChE can be used as surrogate measures of
nervous system AChE activity.
 Because cholinesterase levels vary greatly
between individuals (inter-individual
variability) it is necessary to establish a pre-
exposure baseline functioning level for each
individual in order to determine meaningful
change in cholinesterase levels.

8.  If no baseline exists, and the initial test reading
during the illness episode is within the
laboratory’s normal range, the possibility of
poisoning cannot be excluded.
 Follow-up testing should be done at 1-2 week
intervals until a stable value is evident.
 If the values show an increasing trend, but
eventually reach a stable value 30% or more
above the first AChE level or 40% or more
above the first PChE value, it is evidence that
an overexposure did occur.

9. RBC Cholinesterase Serum Cholinesterase
Low level
Antimalarial drugs
Oral contraceptives
Acute infections
Chronic debilitating disease
Cocaine
Codeine
Dermatomyositis
Genetic deficiency
Hepatic parenchymal d's
Malnutrition
Morphine
Pregnancy
Oral contraceptives
Organic mercury
Succinylcholine
Use of collection tubes
containing fluoride
High level Nephrotic syndromeNephrotic syndrome

10. PRINCIPLE OF S.CHOLINESTRASE
ESTIMATION
 The principle of the method is the measurement of the rate of
production of thiocholine as acetylthiocholine is hydrolyzed.
 This is accomplished by the continuous reaction of the thiol with
dithiobisnitrobenzoate Ion to produce the yellow anion of 5-
mercapto-2-nitro-benzoic acid.
 The rate of color production is measured at 412 nm in a
spectrophotometer.
(enzyme)
Acetylthiocholine ----> thiocholine + acetate
Thiocholine + dithiobisnitrobenzoate(DTNB)-----> yellow color

11. Cholinesterase Monitoring Guidelines
Adapted from guidelines adopted by the states
of Washington and California
 Utilize cholinesterase monitoring for individuals who apply OP
pesticides occupationally on more than 3 consecutive days, or for 30
or more hours within any 30-day period.
 Measure both acetylcholinesterase (red blood cell cholinesterase)
and butyryl cholinesterase (plasma cholinesterase).
 Use the same laboratory and the same methodology for all testing
so that results may be accurately compared.
 Obtain a baseline reading of both measures during the non-exposed
period, at least 30 days since the last exposure to OP pesticides.
Repeat testing every 3-4 weeks during intensive OP and carbamate
application periods.
 Test within 3 days of any 30-day period in which the individual has
met or exceeded the handling hours threshold.
 Compare each reading to the individual’s baseline. Take action as
specified in the following table.

12. Thresholds for cholinesterase
decision-making
Decrease from
baseline
Action
 20% decrease in AChE or
PChE
 Evaluate work practices
 30% decrease in AchE or
40% decrease in PChE
 Remove worker from
exposure to organophosphates
and carbamates until levels
return to within 80% of
baseline

13. SIGNING OUT……