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Clinical Chemistry 2 (Lecture) > Review Journal on Enzymes ("The Physiological Sources of, Clinical Significance of, and Laboratory-Testing Methods for Determining Enzyme Levels" | P) > Flashcards

Review Journal on Enzymes ("The Physiological Sources of, Clinical Significance of, and Laboratory-Testing Methods for Determining Enzyme Levels" | P) Flashcards

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1
Q

What is the characteristic of enzymes?

A

These are organic molecules

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2
Q

What is the fxn of enzymes?

A

These accelerate biochemical rxns but emerge from the rxn unchanged

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3
Q

What is the meaning and purpose of abnormal lvls of plasma enzymes?

A

These are highly suggestive of damaged cells and provide clues to parts of the body that may be involved in disease processes

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4
Q

What are the purposes of measuring the enzyme lvls in the clinical lab?

A

1) To identify the site of damage

2) To quantify the amt of damage

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5
Q

What is the meaning of LD?

A

Lactate dehydrogenase

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6
Q

What is the meaning of AST?

A

Aspartate aminotransferase

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7
Q

What is the meaning of ALT?

A

Alanine aminotransferase

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8
Q

What is the meaning of ALP?

A

Alkaline phosphatase

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9
Q

What is the meaning of GGT?

A

Gamma-glutamyltransferase

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10
Q

What are the characteristics of LD?

A

1) It is a tetrameric enzyme
2) It has 2 distinct subunits
3) It has 6 isoenzymes

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11
Q

What are the 2 distinct subunits present in LD?

A

1) M

2) H

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12
Q

Where can LD be found?

A

1) Cardiac and skeletal muscles
2) Liver
3) Kidneys
4) Erythrocytes
5) Leukocytes
6) Lungs
7) Lymph nodes
8) Spleen
9) Brain

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13
Q

What is the fxn of LD?

A

It catalyzes the redox conversion of lactate to pyruvate / it catalyzes the reversible conversion of pyruvate to lactate in a redox rxn

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14
Q

What are the 6 isoenzymes of LD?

A

1) LD1
2) LD2
3) LD3
4) LD4
5) LD5
* 6) LD6

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15
Q

LD1 consists of what subunits?

A

HHHH subunits

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16
Q

LD2 consists of what subunits?

A

HHHM subunits

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17
Q

Where are LD1 and LD2 predominantly found?

A

1) Heart

2) Erythrocytes

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18
Q

LD3 consists of what subunits?

A

HHMM subunits

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19
Q

Where is LD3 found?

A

In the lungs

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20
Q

LD4 consists of what subunits?

A

HMMM subunits

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21
Q

LD5 consists of what subunits?

A

MMMM subunits

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22
Q

Where are LD4 and LD5 found?

A

In the liver

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23
Q

What is the meaning of MI?

A

Myocardial infarction

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24
Q

What is the meaning of NAD?

A

Nicotinamide adenine dinucleotide

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25
Q

What is the meaning of NADH?

A

Reduced nicotinamide adenine dinucleotide

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26
Q

What are aminotransferases and what is its fxn?

A

These are a grp of enzymes that catalyze the conversion of AAs to 2-oxo-acids by transfer of amino grps

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27
Q

Where are the highest lvls of AST present?

A

1) Liver
2) Cardiac muscle
3) Skeletal muscle

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28
Q

Where are the smaller amts of AST present?

A

1) Kidneys
2) Pancreas
3) Erythrocytes

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29
Q

Where is ALT predominantly present?

A

Liver

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30
Q

What is the fxn of ALP?

A

It catalyzes the hydrolysis of various phosphomonoesters at an alkaline pH

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31
Q

Where are the highest concentrations of ALP found?

A

1) Bone
2) Liver
3) Spleen
4) Intestine
5) Placenta
6) Kidneys

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32
Q

What are the diff isoenzymes of ALP?

A

1) Bone
2) Liver
3) Placenta

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33
Q

Isoenzyme analysis is of limited clinical use due to what?

A

Due to ineffective methods of separation and the availability of more efficient tests for clinical dx

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34
Q

What are the fxns of GGT?

A

1) It catalyzes the transfer of the gamma(sign)-glutamyl residue from gamma(sign)-glutamyl peptides to AAs
2) It is responsible for the catabolism of extracellular glutathione

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35
Q

What is the characteristic of GGT?

A

It is an epithelial enzyme

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36
Q

Where is GGT present?

A

1) Kidney
2) Brain
3) Prostate
4) Pancreas
5) Liver tissue

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37
Q

LD lvls are increased in several disorders due to its what?

A

Due to its presence in a variety of tissues

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38
Q

At what conditions are the most dramatic increase of LD lvls observed?

A

1) Prehepatic disorders
2) Hemolytic disease
3) Testicular and germ cell tumors
4) Acute MI

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39
Q

What happens to LD lvls when in presence of the said conditions where it is increased?

A

1) It increases 12 hrs after an MI
2) It peaks in 2 days
3) It returns back to normal lvls in 7 - 14 days

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40
Q

What LD isoenzyme normally predominate in the blood?

A

Plasma LD2 lvls

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41
Q

What LD isoenzyme follows plasma LD2 in terms of predominating in the blood?

A

LD1 lvls

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42
Q

What happens if there is a presence of damaged cardiac tissue in MI?

A

LD1 lvls increase, w/c triggers a reversal in w/c LD1 lvls become > LD2 lvls

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43
Q

What is the reason why isoenzyme analysis now became outdated?

A

Isoenzyme analysis has now became outdated due to the availability of more sensitive and sp cardiac markers

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44
Q

Give an ex of sp cardiac marker

A

Troponin

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45
Q

Where can troponin be used / help?

A

In terms of the dx of MIs

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46
Q

Currently, laboratorians mostly use LD as what?

A

As a nonspecific screening or monitoring tool

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47
Q

What is the purpose of mostly using LD as a nonspecific screening or monitoring tool by the laboratorians?

A

To determine the extent of tissue damage

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48
Q

What is the reference range for LD?

A

125 - 220 U/L

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49
Q

What are the clinically significant aminotransferases?

A

1) ALT

2) AST

50
Q

What is the purpose of ALT and AST?

A

Both are markers of liver disease

51
Q

What is the comparison bet ALT and AST?

A

ALT is more liver sp > AST

52
Q

At what conditions / disorders are AST lvls significantly increased?

A

1) Skeletomuscular disorders

2) Pulmonary embolism

53
Q

What happens to ALT lvls and what is its relationship w/ AST lvls in cases of acute inflammatory conditions of the liver?

A

ALT lvls are higher > AST lvls

54
Q

Why are ALT lvls higher > AST lvls in cases of acute inflammatory conditions of the liver?

A

Because ALT has a half-life of 16 - 24 hrs

55
Q

Increased ALT lvls have been associated w/ what and what is the result of these accdg to some studies?

A

These lvls have been associated w/ deaths from liver disease and all-cause mortality in some studies

56
Q

What is the reference range for ALT?

A

7 - 45 U/L

57
Q

What is the reference range for AST?

A

5 - 35 U/L

58
Q

ALP lvls are highly increased in cases of what disorders?

A

1) Hepatobiliary disorders

2) Bone disorders

59
Q

ALP lvls are normally increased during what instances?

A

1) Pregnancy

2) Growing children

60
Q

Why are ALP lvls normally increased during pregnancy?

A

Due to placental fraction of ALP

61
Q

Why are ALP lvls normally increased during the growth of children?

A

Due to bone fraction of ALP

62
Q

At what disorders are intestinal ALP lvls increased?

A

Disorders of the:

1) Digestive tract
2) Liver

63
Q

At what condition / disorder are ALP lvls decreased?

A

Inherited hyperphosphatasia

64
Q

The reference range for ALP varies w/ what?

A

1) Age

2) Sex

65
Q

Higher lvls of reference range for ALP are present in what age grp?

A

Younger individuals > older individuals

66
Q

Higher lvls of reference range for ALP are present in what sex?

A

Men > women

67
Q

Why are the reference range for ALP lvls are higher for younger individuals > older individuals and men > women?

A

Probably due to bone-fraction measurements

68
Q

GGT lvls are mainly elevated in what disorders?

A

1) Hepatobiliary disorders

2) Liver disorders

69
Q

GGT lvls are also increased in what instances for pts?

A

1) In pts w/ chronic alcoholism
2) Pts who take enzyme-inducing drugs
3) Pts having pancreatitis
4) Pts having DM

70
Q

What are the exs of enzyme-inducing drugs that can cause increased GGT lvls?

A

1) Warfarin

2) Phenytoin

71
Q

High GGT lvls are also associated w/ what?

A

W/ high rates of all-cause mortality

72
Q

What is the reference range for GGT for men?

A

6 - 55 U/L

73
Q

What is the reference range for GGT for women?

A

5 - 38 U/L

74
Q

Why are the reference range for GGT lvls are lower in females compared to males?

A

Due to higher lvls of estrogen and progesterone

75
Q

What are the characteristics of measurement of enzymes?

A

1) It is standardized
2) It is simple
3) It is inexpensive
4) It requires no special preparation for the pt

76
Q

True or False

Small quantity of enzymes are normally available in the blood

A

True

77
Q

What is done due to the reason that small quantity of enzymes normally available in blood?

A

The rate of rxn is measured photometrically, related to the activity of the enzyme

78
Q

What is the relationship bet enzyme activity and concentration of the enzyme?

A

Enzyme activity is proportional to the concentration of the enzyme

79
Q

What are the preferred type of sx for enzyme analysis?

A

1) Serum

2) Heparinized plasma

80
Q

How can laboratorians measure LD activity and what is its principle?

A

By gauging the A of coenzyme NAD as it is changed to NADH while lactate is oxidized to pyruvate

81
Q

What is the principle of rxn of lactate being oxidized to pyruvate?

A

Lactate + NAD^+ Pyruvate + NADH + H

82
Q

The rxn of lactate being oxidized to pyruvate is derived from what process?

A

Glycolysis

83
Q

What is the purpose of glycolysis?

A

It is the biochemical pathway for metabolism of glucose in all living cells

84
Q

What are the sx considerations and storage considerations for determination of LD lvls?

A

1) Sxs must be free from hemolysis
2) Sxs must be stored at room temp
3) Sx must be analyzed within 48 hrs after sx collection

85
Q

Why must sxs be free from hemolysis in determination of LD lvls?

A

Because LD lvls are 100- to 150-fold higher in RBCs > in serum

86
Q

How are AST and ALT activity measured?

A

By measuring the change in A as aspartate and alanine transfer their amino grp to the appropriate respective alpha(sign)-keto acids

87
Q

What is the coenzyme for rxns in connection w/ AST and ALT activity?

A

Pyridoxal-5-phosphate

88
Q

What is the principle of rxn for AST?

A

Aspartate + alpha(sign)-Ketoglutarate Oxaloacetate + Glutamate

Oxaloacetate + NADH + H^+ + Malate + NAD^+

89
Q

What is the principle of rxn for ALT?

A

Alanine + alpha(sign)-Ketoglutarate Pyruvate + Glutamate

Pyruvate + NADH + H^+ Lactate + NAD^+

90
Q

What is the relationship bet change in A and concentration of AST?

A

Change in A is directly proportional to the concentration of AST

91
Q

What is the relationship bet change in A and concentration of ALT?

A

Change in A is directly proportional to the concentration of ALT

92
Q

ALT and AST rxns are extremely impt for what?

A

Synthesis and degradation of AAs

93
Q

Oxaloacetate and pyruvate are oxidized by what?

A

Tricarboxylic cycle (Krebs cycle)

94
Q

What is the purpose of oxidizing oxaloacetate and pyruvate via Krebs cycle?

A

To provide intermediate products

95
Q

What is the fxn of the intermediate products that came from the oxidation of oxaloacetate and pyruvate via Krebs cycle?

A

To generate energy for living cells

96
Q

What are the sx and storage considerations for determination of AST lvls?

A

1) Sxs must be free from hemolysis
2) For optimal results, sxs must be stored at ref temp
3) Analyze the sx within 3 - 4 days after sx collection

97
Q

What are the sx and storage considerations for determination of ALT lvls?

A

1) For optimal results, sxs must be stored at ref temp

2) The sxs should be analyzed within 3 - 4 days after sx collection

98
Q

Are ALT lvls are affected by any interference from erythrocytes?

A

No, because ALT lvls are unaffected by any interference from RBCs

99
Q

ALP activity is measured by a method devised by what / whom?

A

Bowers and McComb

100
Q

What is involved in the method to measure ALP activity devised by Bowers and McComb?

A

It involves the calculation of activity based on molar absorptivity of p-nitrophenol

101
Q

What is the characteristic of para-nitrophenylphosphate?

A

It is a colorless compound

102
Q

What happens to para-nitrophenylphosphate in measuring the ALP activity (devised by Bowers and McComb)?

A

It is hydrolyzed to a yellow-colored p-nitrophenol

103
Q

Increase in A (in Bowers and McComb) can be measured in what rxn?

A

*p-Nitrophenylphosphate p-Nitrophenol + Phosphate ion

104
Q

What is the relationship bet A of p-nitrophenol and ALP activity?

A

The increase in A of p-nitrophenol is directly proportional to ALP activity

105
Q

What are the sx considerations for ALP analysis?

A

1) Sxs collected must be free of hemolysis
2) Sxs must analyzed soon after collection
3) Pt must not eat a high-fat meal before sx collection
4) Fasting sxs are not recommended because the interference is negligible

106
Q

Why should the pt must not eat a high-fat meal prior to sx collection (in determination of ALP lvls)?

A

Because if the pt ate a high-fat meal prior to sx collection may also cause falsely increased values due to the intestinal fraction for ALP

107
Q

When is GGT activity measured?

A

When gamma(sign)-glytamyl-p-nitroanilide transfer its gamma(sign)-glytamyl residue to glycylglycine

108
Q

When gamma(sign)-glytamyl-p-nitroanilide transfer its gamma(sign)-glytamyl residue to glycylglycine, this results to the formation of what?

A

p-Nitroaniline

109
Q

What is p-Nitroaniline?

A

It is a chromagen

110
Q

What is the principle of rxn for the formation of p-Nitroaniline?

A

gamma(sign)-Glutamyl - p-nitroanilide + Glycylglycine

gamma(sign)-Glutamyl - glycylglycine + p-Nitroaniline

111
Q

What is the relationship bet the A of p-Nitroaniline to the activity of GGT?

A

The A of p-Nitroaniline is directly proportional to the activity of GGT

112
Q

What is the stability of p-Nitroaniline?

A

It is stable in serum sxs for 1 wk at ref temp

113
Q

What is the importance of LD, AST, ALT, ALP, and GGT?

A

These are the enzymes that are clinically significant in various disorders including conditions of the liver

114
Q

At what disorders / conditions are LD lvls most predominant?

A

1) Pre-hepatic disorders

2) Hemolytic disorders

115
Q

Why are LD lvls most predominant in pre-hepatic and other hemolytic disorders?

A

Due to its presence in erythrocytes

116
Q

At what disorders are ALT and AST lvls predominant?

A

Hepatic disorders

117
Q

What is the comparison bet ALT and AST?

A

ALT is more liver sp > AST

118
Q

At what disorders are ALP and GGT increased?

A

Post-hepatic disorders

119
Q

What is the purpose of GGT?

A

It is associated w/ chronic alcoholism

120
Q

What are the importance of increased activity w/ LD, ALT, AST, ALP, and GGT being detected?

A

1) These enzymes provides clues to the source of the clinical problem
2) These can be extremely valuable in the dx of the pt’s condition

Clinical Chemistry 2 (Lecture) (17 decks)

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