MtC Block 2 Assorted Cytochromes and Pathologies

Question 1

Gilbert’s Syndrome

Answer 1

Def. in bilirubin clearance with UGTA1

Question 2

UDP Targets

Answer 2

Hydroxyl, Amine, Thiol

Question 3

Glutathione S–Transferase Targets

Answer 3

Epoxides Primarily, Any Lipophilic Electrophiles

Question 4

Sulftransferase Targets

Answer 4

Uses PAPS to a nucleophile acceptor: Hydroxyl, Amine

Question 5

Benzo[a]pyrene

Answer 5

Example of non-carcinogen that activates into an epoxide derivative and becomes carcinogenic. G-C to T-A mut

Question 6

Xenobiotic Response Elements

Answer 6

Transcriptional regulator of xenobiotic pathways

Question 7

Dioxin

Answer 7

From industrial (paper and pulp) and Agent Orange
Upregulates CYP1A1, UDPGT, GST genes upon binding to Ah receptor
Metabolism of 7 - 15 years, extremely toxic

Question 8

Grapefruit Juice Cytochrome Interaction

Answer 8

CYP3A4, increases effective dosage of calcium blockers, statins; increases CV risk

Question 9

Cruciferous Vegetable Cytochrome Interaction

Answer 9

CYP1A1; reduces effective dosage of polyaromatic hydrocarbons (carcinogens)

Question 10

Iron Deficiency Cytochrome Interaction

Answer 10

Heme deficiency in the entire CYP450 family

Question 11

Vitamin Deficiency Cytochrome Interaction

Answer 11

Riboflavin (B2) deficiency results in lower CYP450 activity (FAD deficiency)

Question 12

Metabolizer Polymorphism Classes

Answer 12

Poor: Lack of activity, 2 deficient alleles
Intermediates: Decreased activity, heterozygous for deficient or reduced activity alleles
Extensive: 2 functional alleles
Ultrarapid: 2+ active or increased activity alleles

Question 13

CYP2D6 Deficiency

Answer 13

Screening required, silent without drug challenge
Necessary to metabolize opioids (i.e. codeine)
CYP2D6 also inhibited by Prozac

Question 14

CYP2C19 Polymorphism

Answer 14

Ethnic differences: ~5% for Caucasians, African-Americans, 13-23% for Asians are poor metabolizers
Plavix needs CYP2C19 to function

Question 15

CYPOR Polymorphism

Answer 15

Embryonic lethality if KO

Deficiency results in Antley-Bixley with steroiogenic abnormalities

Question 16

CYPOR Chain

Answer 16

NADPH -> FAD -> FMN -> Heme

Question 17

Overall Monoxygenase Reaction for P450

Answer 17

RH + O2 + NADPH + H -> ROH + H20 + NADP

Question 18

APAP Breakdown Normal

Answer 18

5% in usually broken down by CYP2E1 to form NAPQI then GST

Rest is by UGT (primarily) and SULT (secondary)

Question 19

Alcoholism with APAP

Answer 19

CYP2E1 is upregulated, more NAPQI

Question 20

N-Acetylcysteine (NAC) with APAP

Answer 20

Glutathione synth is upregulated (major), also promotes SULT and has a direct interaction with NAPQI (minor)