EXAM 4

Question 1

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

Answer 1

1

Question 2

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

Answer 2

1

Question 3

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

Answer 3

1

Question 4

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

Answer 4

1

Question 5

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

Answer 5

1

Question 6

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

Answer 6

1

Question 7

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

Answer 7

2

Question 8

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

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

Answer 8

4

Question 9

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

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

Answer 9

1

Question 10

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

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

Answer 10

3

Question 11

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

Answer 11

4

Question 12

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

Answer 12

1

Question 13

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

Answer 13

2

Question 14

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

Answer 14

1

Question 15

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

Answer 15

3

Question 16

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

Answer 16

1

Question 17

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

Answer 17

2

Question 18

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

Answer 18

1

Question 19

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

Answer 19

3

Question 20

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

Answer 20

1

Question 21

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

Answer 21

1

Question 22

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

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

Answer 22

2

Question 23

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

Answer 23

T

Question 24

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

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

Answer 24

5

Question 25

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

Answer 25

1 A 2 B 3 D 4 C

Question 26

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

Answer 26

1.) ethanol + NAD+ -> acetaldehyde + NADH uses alcohol dehydrogenase 2. ) acetaldehyde + NAD+ -> acetate + NADH uses aldehyde dehydrogenase 3. ) ethanol + NADPH -> acetaldehyde + NADP+ uses cytochrome P450 CYP2E1

Question 27

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 ```

Answer 27

1. A 2. D 3. B 4. E 5. C 6. F

Question 28

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

Answer 28

2

Question 29

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)

Answer 29

1.

Question 30

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

Answer 30

3

Question 31

Porphyrin accumulation indicates: 1. ) All of these responses 2. ) decreased ability to oxygenate cells 3. ) decreased CYP enzymes 4. ) decreased ability to degrade toxins

Answer 31

1

Question 32

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

Answer 32

3

Question 33

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

Answer 33

1

Question 34

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

Answer 34

2

Question 35

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

Answer 35

2

Question 36

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

Answer 36

1

Question 37

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

Answer 37

4

Question 38

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

Answer 38

2

Question 39

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

Answer 39

1

Question 40

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

Answer 40

1

Question 41

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

Answer 41

2

Question 42

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

Answer 42

1

Question 43

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

Answer 43

4

Question 44

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

Answer 44

1

Question 45

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

Answer 45

1

Question 46

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)

Answer 46

1

Question 47

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

Answer 47

1

Question 48

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

Answer 48

1

Question 49

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

Answer 49

2

Question 50

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

Answer 50

1

Question 51

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

Answer 51

1

Question 52

How is Hippuric acid created?

Answer 52

Conjugation of benzoic acid with glycine

Question 53

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

Answer 53

PAPS