Term
| Sulfation often competes with what other Phase II metabolic pathway? |
|
Definition
|
|
Term
| Sulfation occurs most commonly in which type of substrates? |
|
Definition
|
|
Term
| Sulfation increases or decreases polairty? |
|
Definition
|
|
Term
T/F
APAP can undergo Phase II directly |
|
Definition
True
Sulfation (20%) Glucuronidation (70%) |
|
|
Term
T/F
Glutathione conjugation occurs via Phase I reaction |
|
Definition
|
|
Term
| What is the primary role of glutathione conjugation? |
|
Definition
Detoxification
it can increase polarity but not its primary role |
|
|
Term
| Glutathione conjugates may be further metabolized into____. |
|
Definition
mercapturic acids
(N-acetylcysteine) |
|
|
Term
T/F
Glutathione is a dipeptide (two peptides) |
|
Definition
FALSE
tripeptide (Glu-Cys-Gly) |
|
|
Term
On which atom does the glutathione conjugation occur?
|
|
Definition
The S (sulfur)
See pic page 20 |
|
|
Term
| Which pathway in the metabolism of APAP leads to toxicity? |
|
Definition
|
|
Term
T/F
NAPQI (the toxic metabolite of APAP) is produced even with a therapeutic doses |
|
Definition
|
|
Term
If a person ingests 10 g of APAP, how soon must the antidote be given?
What is the antidote? |
|
Definition
within 8 hrs
Acetylcysteine |
|
|
Term
| How do people develop liver damage from overdosing on APAP? (pertaining to metabolic pathways) |
|
Definition
the pathways that produce non-toxic metabolites (Glucuronidation, Sulfation) become saturated and APAP gets metabolized into the toxic product.
The glutathione pathway then becomes saturated and can no longer detoxify the toxic metabolite. |
|
|
Term
T/F
Acetylation increases the polarity of the substrate |
|
Definition
|
|
Term
What molecule is tranfered to the substrate in Acetylation?
What is the most common substrate? |
|
Definition
Acetyl group -COCH3
Aromatic Amines |
|
|
Term
| Explain how an acetylated compound is less polar that the original subtrate. |
|
Definition
The substrate is an amine (-NH2) and is normally ionized (polar) at physiological pH.
Adding an acetyl group makes it no longer ionized (-COCH3) |
|
|
Term
What role does methylation play?
Does it enhance polarity?
|
|
Definition
Endogenous, in the biosynthesis /regulation of neurotransmitters
Does NOT enhance polarity |
|
|
Term
| What are possible substrates for methylation? |
|
Definition
|
|
Term
| What drugs can be metabolized by methylation? |
|
Definition
| drugs structurally related to neurotransmitters |
|
|
Term
| If a drug undergoes methylation metabolism should the logP inc or dec? |
|
Definition
| Increase, because decreasing polarity |
|
|
Term
T/F
Methylation plays a major role in drug metabolism |
|
Definition
FALSE
limited role...only drugs structurally similar to neurotransmitters |
|
|
Term
| What AA is most often transferred in Amino Acid Conjugation? |
|
Definition
|
|
Term
| Why is AA conjugaiton relatively uncommon? |
|
Definition
| the substrates are limited because there is limited free AA in the body |
|
|
Term
| What is the substrate for AA conjugation? |
|
Definition
|
|
Term
What factors can affect drug metabolism?
|
|
Definition
| Age, Sex, other drugs, Polymorphisms, Species, Routes of administration, diseases |
|
|
Term
T/F
Even though there are differences in drug metabolism, they may not be of clinical significance |
|
Definition
|
|
Term
T/F
Children metabolize APA by sulfation b/c their glucuronidation pathway is not fully developed |
|
Definition
TRUE
adult levels at age 9 |
|
|
Term
| Which CYP enzyme is highly polymorphic? |
|
Definition
CYP2D6
it has 4 phenotypes |
|
|
Term
| What is the genotype for intermediate metabolizers? (alleles) |
|
Definition
| one inactive and one wildtype allele |
|
|
Term
| What is the genotype for ultrarapid metabolizers? |
|
Definition
|
|
Term
| What is the genotype for poor metabolizers? |
|
Definition
| both alleles code for inactive enzyme |
|
|
Term
T/F
If a drug is poorly metabolized in one species it is safe to say that it will be poorly metabolized in other species as well. |
|
Definition
FALSE
it depends on the drug and how it is metabolized...not necessarily the same for all species |
|
|
Term
Match pathway with its cofactor
1) acetyl-CoA
2) SAM
3) PAPS
4) UDPGA |
|
Definition
1) acetyl-CoA: Acetylation
2) SAM: Methylation
3) PAPS: Sulfation
4) UDPGA: Glucuronidation |
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|
