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Clinical Chemistry > Miscellaneous Enzymes > Flashcards

Miscellaneous Enzymes Flashcards

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0
Q

Where is acetylcholine synthesized?

A

At nerve endings

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1
Q

What reaction does cholinesterase catalyze?

A

The hydrolysis of choline esters (acetylcholine)

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2
Q

What purpose does acetylcholine serve?

A

Acts to transmit impulses from nerve to muscle fibers

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3
Q

What is the cholinesterase mechanism?

A

Destroys acetylcholine after the impulse has been transmitted. Allows the nerve to repolarize so additional impulses may be transmitted.

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4
Q

What would happen if cholinesterase is deficient?

A

Without the enzyme, the nerve would remain electrically charged and further conduction would be impossible.

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5
Q

What is the formal name for ‘true cholinesterase?’

A

Acetylcholinesterase or AChE

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6
Q

Where is true cholinesterase found?

A

RBCs, lungs, spleen, nerve endings and the gray matter of the brain; bound to cell membranes

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7
Q

What is the formal name for ‘pseudocholinesterase?’

A

Acylcholine acylhydrolase (SChE, PChE)

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8
Q

Where does most of the plasma pseudocholinesterase come from?

A

The liver

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9
Q

Where is pseudocholinesterase found?

A

In the serum, heart, liver, pancreas, white matter of the brain (cell cytoplasm)

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10
Q

Do increased levels of pseudocholinesterase have clinical significance?

A

No

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11
Q

What disorders do decreased pseudocholinesterase levels characterize?

A

Organic phosphate insecticide poisoning, hepatocellular disease, genetic defects in the synthesis of the enzyme

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12
Q

What is the “normal” phenotype for pseudocholinesterase?

A

UU

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13
Q

What two pseudocholinesterase phenotypes result in reduced catalytic activity?

A

AA and FF

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14
Q

What pseudocholinesterase phenotype results in a completely dysfunctional enzyme?

A

SS

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15
Q

What happens when there is a genetic defect in pseudocholinesterase synthesis?

A

Atypical forms of the enzyme are created and are weakly active or inactive

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16
Q

3 types of organic phosphate insecticides

A

Parathion, sarin and tetraethyl pyrophosphate

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17
Q

How much pseudocholinesterase must be inhibited before the symptoms of organic phosphate insecticide poisoning manifest?

A

40%

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18
Q

How can functionally abnormal variants of pseudocholinesterase be characterized?

A

Testing their response to either dibucaine or fluoride

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19
Q

In relation to pseudocholinesterase variants, how will fluoride and dibucaine affect them?

A

They are competitive inhibitors. Variant pseudocholinesterase has a decreased affinity for dibucaine and fluoride. Variants will not be affected while usual forms will be affected.

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20
Q

Which pseudocholinesterase variant is less susceptible to dibucaine?

A

AA

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21
Q

Which pseudocholinesterase variant is less susceptible to fluoride?

A

FF

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22
Q

What is the dibucaine number?

A

% of cholinesterase activity that is inhibited when dibucaine is added to the assay

23
Q

What is the fluoride number?

A

% of cholinesterase activity that is inhibited when fluoride is added to the assay

24
Q

Are pseudocholinesterase variant isoenzymes less or more effective catalysts over the usual forms?

A

Less effective

25
Q

Is the affinity for the substrate and competitive inhibitors increased or decreased for pseudocholinesterase isoenzyme variants?

A

They are decreased

26
Q

Dibucaine/Fluoride number formula

A

[1-(ACTi/ACTu)] x 100%

ACTi=Activity with inhibitor
ACTu=Activity without inhibitor

27
Q

What is the normal % inhibition with both dibucaine and fluoride for pseudocholinesterase activity?

A

80-90% with dibucaine and fluoride

28
Q

What is % inhibition for the AA pseudocholinesterase isoenzyme?

A

10-30% with dibucaine

29
Q

What is the % inhibition for the FF pseudocholinesterase isoenzyme?

A

10-30% with fluoride

30
Q

What does a low dibucaine/fluoride number indicate?

A

Reflects decreased enzyme activity

31
Q

Why would serum pseudocholinesterase be measured?

A

To screen preoperatively for sensitivity to the muscle relaxant, succinyldicholine

32
Q

Why is succinyldicholine used?

A

Used to temporarily paralyze the diaphragm to facilitate intubation for anesthesia

33
Q

What effect does pseudocholinesterase have on succinyldicholine?

A

Pseudocholinesterase rapidly deactivates succinyldicholine. Effect of the drug lasts 30-50 minutes.

34
Q

Why do patients needs to be screened for succinyldicholine sensitivity?

A

If a patient has low levels of pseudocholinesterase or allelic variants that have low activity, this may result in prolonged apnea and the patient may require a respirator until the drug is cleared by other mechanisms.

35
Q

How is serum pseudocholinesterase measured?

A

Thiocholine esters are hydrolyzed by pseudocholinesterase to form a colored product, which is then measured.

36
Q

What type of specimen is preferred for pseudocholinesterase analysis?

A

Serum or heparinized plasma

37
Q

How long is the sample for pseudocholinesterase stable?

A

Sample is stable for weeks at room temp

38
Q

What does RBC cholinesterase reflect?

A

It reflects true cholinesterase activity.

39
Q

What does a decreased cholinesterase signify?

A

It is decreased in paroxysmal nocturnal hemoglobinuria.

40
Q

What does Angiotensin Converting Enzyme (ACE) do?

A

It catalyzes the conversion of angiotensin I to angiotensin II.

41
Q

Why is Angiotensin Converting Enzyme (ACE) important?

A

It is vital in the control of aldosterone secretion and the regulation of blood pressure.

42
Q

In what conditions would Angiotensin Converting Enzyme (ACE) be elevated?

A

Sarcoidosis, Gaucher’s Disease, Hodgkin’s Disease, alcoholic cirrhosis, leprosy, histoplasmosis

43
Q

How specific are Angiotensin Converting Enzyme (ACE) levels in the study of hypertension?

A

They are not very specific for hypertension so levels aren’t useful.

44
Q

Where does Angiotensin Converting Enzyme (ACE) originate?

A

Lungs

45
Q

In what condition will Angiotensin Converting Enzyme be increased from 50-80%?

A

Sarcoidosis

46
Q

What type of enzyme is Glucose-6-Phosphate Dehydrogenase?

A

Oxidoreductase

47
Q

In what metabolic pathway does G6PD play an important role?

A

Hexose Monophosphate Pathway

48
Q

What reaction mechanism does G6PD catalyze?

A

It catalyzes the transfer of hydrogen ions from Glucose-6-Phosphate to NADP, producing NADPH.

49
Q

Where is G6PD found?

A

It is found in most cells.

50
Q

Clinically significant G6PD is found where?

A

RBCs

51
Q

What does deficiency of G6PD result in?

A

Hemolysis of RBCs

52
Q

Describe the role G6PD plays in the RBC.

A

In normal RBCs, drugs and other metabolites are oxidized to oxyhemoglobin. A byproduct of this reaction is hydrogen peroxide. Hydrogen peroxide is then eliminated in a reaction with reduced glutathione. To regenerate reduced glutathione after this, NADPH is needed. As G6PD is needed to produce the NADPH, NADPH will not be produced if G6PD is deficient. Reduced glutathione doesn’t remove the hydrogen peroxide and it builds up in the cell, causing defects in the cell membrane which leads to hemolysis.

53
Q

Is G6PD an inherited or acquired deficiency?

A

Inherited

54
Q

What situations can incite a G6PD deficiency related hemolytic episode?

A

Ingestion of certain drugs (like primaquine), ingestion of fava beans, infections

55
Q

Elevations of RBC G6PD are seen in:

A

Pernicious anemia and thrombocytopenic purpura

56
Q

Elevations of serum G6PD are seen in:

A

After an AMI or pulmonary infarct

Clinical Chemistry (6 decks)

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