EXAM 4 Flashcards

1
Q

The enzyme CPOX (coproporphyrinogen oxidase) converts coproporphyrinogen III to protoporphyrinogen IX and is blocked by the heavy metals.

  1. ) Lead and Mercury
  2. ) Mercury and Arsenic
  3. ) Arsenic and Cadmium
  4. ) Lead and Cadmium
A

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2
Q

The heavy metal ______ causes preferential elevation in Copro I: Copro III because it blocks the early steps of UROD decarboxylation, leading to the accumulation of uroporphyrinogen I, which converts to coproporphyrinogen I.

  1. ) Arsenic
  2. ) Mercury
  3. ) Lead
  4. ) Cadmium
A

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3
Q

UROD is blocked by both ___(a)___ . The difference between the two heavy metals is that ___(b)___ causes high pentacarboxyporphyrin because it slows UROD down, making the last decarboxylation step difficult.

  1. ) (a) As and Hg, (b) Hg
  2. ) (a) As and Hg, (b) As
  3. ) (a) Hg and Pb, (b) Pb
  4. ) (a) Pb and As, (b) As
A

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4
Q

Elevations in BUN indicate increased load of ammonia. Checking the OA profile, you find high orotate levels, which could indicate there is a genetic SNP in the enzyme _____________.

  1. ) ornithine transcarbamoylase (OTC)
  2. ) argininesuccinate synthetase (ASS)
  3. ) argininosuccinate lyase (ASL)
  4. ) arginase
A

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5
Q

AST, ALT, CPK, and _____ are all enzymes that can be indicators of liver damage, which in turn means impaired liver function.

  1. ) gamma-glutamyl transpeptidase
  2. ) gamma-glutamyl cyclotransferase
  3. ) pyroglutaminase
  4. ) GSH synthase
A

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6
Q

High ammonia can be from impaired degradation of proteins, impaired urea cycle, and even exercise. High ammonia can also be indicative of:

  1. ) all of these responses
  2. ) bacterial overgrowth
  3. ) excessive glutamine intake
  4. ) deficiency of arginine
A

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7
Q

Alcohol, high protein diets, high brassica diets, saturated fats, steroid hormones, charcoal-broiled meats (AGEs), oranges, exhaust fumes, pesticides, niacin and riboflavin all have the following thing in common:

  1. ) they inactivatecCYP enzymes
  2. ) they induce CYP enzymes
  3. ) they increase urea cycle intermediates
  4. ) they decrease urea cycle intermediates
A

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8
Q

Clearance of the compound _________ is used to determine activity level of phase I detoxification.

  1. ) benzoic acid
  2. ) acetaminophen
  3. ) acetylsalicylic acid
  4. )caffeine
A

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9
Q

One of the three major pathways of phase I detoxification includes:

  1. ) Hydroxylation
  2. ) Decarboxylation
  3. ) Acetylation
  4. ) Sulfation
A

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10
Q

CYP1A2 and CYP2E1 are important to remember because these pathways are activated by:

  1. ) alcohol
  2. ) estrogen
  3. ) caffeine
  4. ) cortisol
A

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11
Q

Phase II detoxification involves conjugation of a water soluble constituent to a functional group on the toxin. These conjugation reactions can occur:

  1. ) on carboxyl, hydroxyl or amine groups
  2. ) multiple times creating many different types of metabolites
  3. ) along different pathways depending upon substrate concentration
  4. ) all of these responses
A

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12
Q

A low rate of caffeine clearance can indicate:

  1. ) all of these responses
  2. ) loss of liver function
  3. ) low level of toxin exposure
  4. ) genetic SNPs lowering phase I detox capacity
A

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13
Q

The activated form of glucuronic acid, ____(a)____ , is used in glucuronidation reactions and is produced from the oxidation of ____(b)____ .

  1. ) (a) ADP-glucuronic acid, (b) ADP-glucose
  2. ) (a) UDP-glucuronic acid, (b) UDP-glucose
  3. ) (a) GDP-glucuronic acid, (b) GDP-glucose
  4. ) (a) TDP-glucuronic acid, (b) TDP-glucose
A

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14
Q

The major and most common route for xenobiotic phase II metabolism is ___________ and it accounts for the majority of conjugated metabolites found in urine and bile.

  1. ) glucuronidation
  2. ) sulfation
  3. ) acetylation
  4. ) GSH conjugation
A

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15
Q

Localization of the enzyme ____(a)____ in the ER right next to the cytochrome P450 enzymes enables it to reach the phase I metabolites before other phase II detox enzymes. The isoform ____(b)____ acts on the highest number of substrates (40%), including bile, morphine, and codeine.

  1. ) (a) glutathione-S-transferase, (b) GSTM1
  2. ) (a) N-acetyl-transferase, (b) NAT2
  3. ) (a) UDP-glucuronyl transferase, (b) UGT2B4 (=2B7)
  4. ) (a) sulfotransferase, (b) SULT1
A

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16
Q

GSH can conjugate with electrophiles through the enzyme ___________ to reduce the reactivity of these harmful substances.

  1. ) glutathione-S-transferase (GST)
  2. ) glutamyl-transferase
  3. ) cysteinyl-glycinase
  4. ) acetylase
A

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17
Q

The sulfation pathway prevails over glucuronidation when there are adequate levels of sulfate and ATP with __________ of xenobiotics.

  1. ) high levels
  2. ) low levels
  3. ) multiple types
A

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18
Q

There are two major types of sulfotransferases. One type is membrane-bound in the golgi apparatus and sulfates GAGs and glycoproteins, while the other is located in the __________ and conjugates steroids, catecholamines, T4, bile acids, and xenobiotics.

  1. ) cytosol
  2. ) nucleus
  3. ) smooth ER
  4. ) mitochondria
A

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19
Q

The most common amino acid used in conjugation reactions is __________, which is the preferential detoxification pathway of benzoic acid.

  1. ) taurine
  2. ) glutamine
  3. ) glycine
  4. ) cysteine
A

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20
Q

The rate of acetylation is important in detoxification because:

  1. ) slow acetylators accumulate higher blood concentrations of active drugs
  2. ) fast acetylators accumulate higher blood concentrations of active drugs
  3. ) fast acetylators eliminate the drug more slowly
  4. ) slow acetylators eliminate drugs more quickly
A

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21
Q

Methylation typically works on endogenous constituents, with O-methyl metabolites have ___(a)____ activity than the original molecule. The active methyl group used in methylation reactions is ____(b)____.

  1. ) (a) greater, (b) SAMe
  2. ) (a) lesser, (b) SAMe
  3. ) (a) greater, (b) 5MHTF
  4. ) (a) lesser, (b) 5MTHF
A

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22
Q

Biomethylation to remove arsenic requires the use of ____ SAMe as a methyl donor.

  1. ) 1
  2. ) 2
  3. ) 3
  4. ) 4
A

2

23
Q

True/False: Oral challenge with aspirin reveals higher glycine conjugate than glucuronides. This is a normal interpretation.

A

T

24
Q

Oral challenge with acetaminophen reveals increased glutathione conjugation with low sulfate and glucuronide conjugation. This person:

  1. ) would benefit from sodium sulfate and NAC
  2. ) would benefit from reduced toxin exposure
  3. ) would benefit from oleic acid (olive oil)
  4. ) all of the above
A

5

25
Q

Alcohol can deplete numerous nutrients. Match the nutrient depletion and the type of symptom/problem that can occur when that nutrient is depleted.

  1. ) Depletion of vitamins B1 and B6 causes
  2. ) Depletion of vitamins B6 and B9 causes
  3. ) Depletion of vitamin B1 causes
  4. ) Depletion of vitamin D causes

A neurological symptoms
B hematological symptoms
C osteoporosis.
D Wernicke-Korsakoff syndrome

A

1 A
2 B
3 D
4 C

26
Q

Match the pathways of alcohol degradation with the appropriate enzyme.

  1. ) ethanol + NAD+ -> acetaldehyde + NADH
  2. ) acetaldehyde + NAD+ -> acetate + NADH
  3. ) ethanol + NADPH -> acetaldehyde + NADP+

Alcohol dehydrogenase
Cytochrome p450 cyp2e1
Aldehyde dehydrogenase

A

1.) ethanol + NAD+ -> acetaldehyde + NADH
uses alcohol dehydrogenase

  1. ) acetaldehyde + NAD+ -> acetate + NADH uses aldehyde dehydrogenase
  2. ) ethanol + NADPH -> acetaldehyde + NADP+ uses cytochrome P450 CYP2E1
27
Q

Match the appropriate detox function with the specific nutrient:

  1. ) toxic metal binding & antioxidant protection
  2. ) hepatic conjugation substrates
  3. ) glutathione regeneration
  4. ) methyl donors
  5. ) lead protection
  6. ) stimulate Phase I and Phase II detox
A. vitamin C
B. NAC, Se, Mn, Cu, Zn 
C. Calcium 
D. glycine, sulfate 
E. Met, SAMe
F. Cruciferous veggies
A
  1. A
  2. D
  3. B
  4. E
  5. C
  6. F
28
Q

The definition of ________ is: a term used when products of detoxification processes are more toxic than the original substance.

  1. ) Detoxification
  2. ) Biotoxification
  3. ) Toxicology
  4. ) Hormesis
A

2

29
Q

One of the phthalate esters used in plastic wrap to cover foods can lead to decreased kidney function, increased cysts, increased peroxisome proliferation and even liver cancer in rats. This is a concern to humans because ______ is used in plastic tubing for hemodialysis.

  1. ) Di(2-ethylhexyl) phthalate (DEHP)
  2. ) Dimethyl phthalate (DMP)
  3. ) Diethyl phthalate (DEP)
  4. ) Polyethylene terephthalate (PETE)
A

1.

30
Q

Toxins can cause cell injury by interfering with DNA regulatory mechanisms, increasing oxidative stress, and altering enzymatic function. If the damage is extensive and cannot be easily repaired, the DNA itself will be damaged, as indicated by a rise in _________.

  1. ) Ammonia
  2. ) Pyroglutamate
  3. ) 8OHDG
  4. ) Cresol
A

3

31
Q

Porphyrin accumulation indicates:

  1. ) All of these responses
  2. ) decreased ability to oxygenate cells
  3. ) decreased CYP enzymes
  4. ) decreased ability to degrade toxins
A

1

32
Q

Precoproporphyrin may elevate when __________ blocks the last step of UROD, leading to the accumulation of pentacarboxyporphyrinogen, which gets converted by CPOX to precoproporphyrin.

  1. ) Arsenic
  2. ) Lead
  3. ) Mercury
  4. ) Cadmium
A

3

33
Q

Elevations in total bilirubin levels indicate impaired degradation of heme as seen in Gilbert’s syndrome. This indicates impaired ________, a pathway in phase II detoxification.

  1. ) Glucuronidation
  2. ) acetylation
  3. ) sulfation
  4. ) glutathione conjugation
A

1

34
Q

Cytochrome P450 enzymes function in the hydroxylation reactions for the activation of (a)__________ and in the microsomal system located in the (b)_________ for the detoxification of xenobiotics.

  1. ) (a) vitamin A, (b) peroxisome
  2. ) (a) vitamin D, (b) smooth ER
  3. ) (a) vitamin E, (b) lysosome
  4. ) (a) vitamin C, (b) rough ER
A

2

35
Q

High caffeine clearance indicates:

  1. ) down regulation of phase I detox
  2. )up regulation of phase 1 detox
  3. ) reduction of oxidation damage
  4. ) low liver function
A

2

36
Q

Phase II detoxification involves conjugation of a water soluble constituent to a functional group on the toxin. These conjugation reactions occur:

  1. ) All of these responses
  2. ) on carboxyl, hydroxyl, or amine groups
  3. ) multiple times creating many different types of metabolites
  4. ) along different pathways depending upon substrate concentration
A

1

37
Q

Immune responses can occur from the creation of __________, like when acyl groups migrate from C1-acyl glucuronides to another protein, covalently bond this new protein, and create a substrate that is now considered foreign and antigenic to the body.

  1. )Complement
  2. ) immunoglobulins
  3. ) antibody-antigen complexes
  4. ) Haptens
A

4

38
Q

Amino acid conjugation requires two steps. The first step is activation of the xenobiotic carboxylic acid using the enzyme (a)________, which requires ATP and (b) ____________.

  1. ) (a) transacetylase, (b) B5
  2. ) (a) acyl synthetase, (b) B5
  3. ) (a) acyl synthetase, (b) P5P
  4. ) (a) transacetylase, (b) P5P
A

2

39
Q

Methylation for single carbon transfer is needed in far greater quantities for (a)________ then for (b)_____________.

  1. ) (a) detoxification, (b) catecholamine biosynthesis
  2. ) (a) telomere protection, (b) detoxification
  3. ) (a) catecholamine biosynthesis, (b) detoxification
  4. ) (a) histamine inactivation, (b) detoxification
A

1

40
Q

The Hormesis Model may be a better indicator of dose-response curves of many toxins because many substances have:

  1. ) All of the above
  2. ) Biphasic responses
  3. ) Beneficial and toxic doses
  4. ) Opposite responses dependent upon dosage
A

1

41
Q

Two major types of organotoxins are xylene and phthalates. Since both can be stored in adipose, measuring the hepatic detoxification product ________________ in the urine, can reveal that xylene is still being processed long after the initial exposure.

  1. ) Hippurate
  2. ) 2 methyl Hippurate
  3. ) Benzoate
  4. ) Sodium benzoate
A

2

42
Q

Methylation for single carbon transfer is needed in far greater quantities for (a)________ then for (b)_____________.

  1. ) (a) detoxification, (b) catecholamine biosynthesis
  2. ) (a) telomere protection, (b) detoxification
  3. ) (a) catecholamine biosynthesis, (b) detoxification
  4. ) (a) histamine inactivation, (b) detoxification
A

1

43
Q

Mutations in the SN1-SN2 transporter can lead to elevations in what 3 AA?

  1. ) Gln, Asn, His
  2. ) Glu, Asn, His
  3. ) Glu, Asp, His
  4. ) Gln, Asp, His
A

4

44
Q

High caffeine clearance indicates:

  1. ) upregulation of phase I detox
  2. ) downregulation of phase 1 detox
  3. ) reduction of oxidation damage
  4. ) low liver function
A

1

45
Q

Cytochrome P450 enzymes function in the hydroxylation reactions for the activation of (a)__________ and in the microsomal system located in the (b)_________ for the detoxification of xenobiotics.

  1. ) (a) vitamin D, (b) smooth ER
  2. ) (a) vitamin A, (b) peroxisome
  3. ) (a) vitamin E, (b) lysosome
  4. ) (a) vitamin C, (b) rough ER
A

1

46
Q

One of the phthalate esters used in plastic wrap to cover foods can lead to decreased kidney function, increased cysts, increased peroxisome proliferation and even liver cancer in rats. This is a concern to humans because ______ is used in plastic tubing for hemodialysis.

  1. ) Di(2-ethylhexyl) phthalate (DEHP)
  2. ) Dimethyl phthalate (DMP)
  3. ) Diethyl phthalate (DEP)
  4. ) Polyethylene terephthalate (PETE)
A

1

47
Q

Treatments to reduce AGEs and ALEs include:

  1. ) All of these responses
  2. ) Antioxidants to reduce oxidation
  3. ) Phase I and II detox to remove RCOs
  4. ) Activation of lysosome degradation
  5. ) Normalizing plasma glucose levels
A

1

48
Q

Two major types of organotoxins are xylene and phthalates. Since both can be stored in adipose, measuring the hepatic detoxification product ________________ in the urine, can reveal that xylene is still being processed long after the initial exposure.

  1. ) 2-methylhippurate
  2. ) Hippurate
  3. ) Benzoate
  4. ) Sodium benzoate
A

1

49
Q

Testing toxin load can be difficult depending upon the type of toxin and where it prefers to deposit. For instance, non-polar organotoxins preferentially deposit in _____(a) tissue and may require a ____ (b) because they quickly clear from blood and urine.

  1. ) (a) Muscle, (b) muscle biopsy
  2. ) (a) Adipose, (b) fat biopsy
  3. ) (a) bone, (b) bone biopsy
  4. ) (a) synovium, (b) synovial aspirate
A

2

50
Q

Toxic insults can be addictive in nature. Which of the following could lead to synergistic effects of toxic insults?

  1. ) All of these reasons
  2. ) Reduced nutrients
  3. ) Multiple toxins
  4. ) Poor diet
  5. ) Pharmaceutical drugs
  6. ) Genetic SNPs
A

1

51
Q

The insecticide DDT, a chlorinated hydrocarbon pesticide, has been banned in the USA since the 1970s but is still causing toxic side effects today because it is:

  1. ) All of these responses
  2. ) A persistent toxin
  3. ) Bioaccumulative
  4. ) Still used overseasterm-147
A

1

52
Q

How is Hippuric acid created?

A

Conjugation of benzoic acid with glycine

53
Q

What is the activated form of sulfate needed for sulfate conjugation?

A

PAPS