Exam 3: 502 - Cofactors, Inhibitors, Cyp Naming, Inducers

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Name cofactor and reaction

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GSH
glutathione
Glutathione conjugation

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S-adenosylmethionine (SAM)
Catechol methylation

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Uridine diphosphate glucuronic acid (UDP-GA)
Glucuronide conjugation

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Acetyl Coenzyme-A
N-acetyl conjugation

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Glycine
Amino acid conjugation

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Glutamine
Amino acid conjugation

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Alcohol Dehydrogenase (AD)
Target(s):
Rxn:
Product:.

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Alcohol
Oxidation
ROH → R(C=O)H

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Aldehyde Dehydrogenase (ADH)
Target:
Rxn:
Product:.

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Aldehyde
Oxidation
R(C=O)H → R(C=O)OH

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ALD/NADH Reductase
Target(s):
Rxn:
Product:.

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Aldehyde/Ketone
Reduction
R(C=O)H → ROH
R(C=O)R → ROH

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Amidase
Target(s):
Rxn:
Product:.

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Amide
Hydrolysis
R(C=O)NH → R(C=O)H + RNH

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CYP450 Desaturation
Target(s):
Rxn:
Product:.

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Alkanes
Oxidation
CH3-CH2- → CH2=CH-

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CYP450 Epoxidation
Target(s):
Rxn Type:
Product:

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Alkene
Oxidation
Catechol; water attacks carbon of
epoxide

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CYP450 Deamination
Target(s):
Rxn Type:
Product:

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Amine
Oxidation
R2C-NH2 → R2C=O

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CYP450 Dealkylation (N, O, & S)
Target(s):
Rxn Type:
Product:

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N/O/S--Alkyl
Oxidation
N/O/S-CH3 → -H

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CYP450 Hydroxylation
Target(s):
Rxn Type:
Product:

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Aromatic
Oxidation
+ OH (Benzylic > Allylic > ω > ω-1)

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CYP450 Dehalogenation
Target(s):
Rxn Type:
Product:

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R2C(OH)-X
Oxidation
R2C(OH)-Br → R2C=O

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Epoxide Hydrolase
Target(s):
Rxn Type:
Product:

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Alkene
Hydrolysis
Epoxide → diol

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Esterase
Target(s):
Rxn Type:
Product:

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Ester
Hydrolysis
R(C=O)OR → R(C=O)OH + ROH (many as prodrugs-simple + fast metab)

*hydrolyzed faster than amides due to resonance and partial double bond

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FMO (Flavin Monooxygenase)
Target(s):
Rxn Type:
Product:

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N/S centers → N-->O (N/S) shares both e's)
Oxidation
N/S centers → N-->O (N/S)

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MAO (Monoamine Oxidase)
Target(s):
Rxn Type:
Product:

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Amine
Oxidation
R-NH → R(C=O)H + NH3

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Reductase (Alkene)
Target(s):
Rxn Type:
Product:

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Alkene
Saturation
Alkane

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Reductase (Nitro)
Target(s):
Rxn Type:
Product:

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R-NO2/AZO Grp
Reduction
-NO2 →-NH2, also cleaves N=N bond

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Reductase (Sulfoxide)
Target(s):
Rxn Type:
Product:

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Sulfoxide
Reduction
R(S=O)R' → RSR' (Sulfoxide → Sulfide)

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Xanthine Oxidase (XO)
Target(s):
Rxn Type:
Product:

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Purine + -OH
(Gout)

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Sulfate conjugation

Target:
Enz:
Cofactor:
Product:

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Enzymes: Sulfotransferase (Cytosolic)

Cofactor: 3’-Phosphoadenosine-5’-phosphosulfate (PAPS)

Phenol, alcohol, some amines, NO FKING CBOX ACIDS

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Glucuronide conjugation

Target:
Enz:
Cofactor:
Product:

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Enzymes: Glucuronosyl transferase (Microsomal)

Cofactor:
Uridine diphosphate glucuronic acid (UDP-GA)
Liver, intestine, kidney

Target functional group:
-Alcohols & Phenols
-Aromatic & Some Aliphatic Carboxylic Acids
-Amines
-Sulfhydryls (i.e., thiol)

Products: target functional group with a oxygen heterocyclic chair.

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N-Acetyl conjugation

Target:
Enz:
Cofactor:
Product:

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Enzymes: N-Acetyltransferase (NAT-two isoforms)
Liver (cytosolic)

Cofactor: Acetyl CoA

Target functional group:
Amines
Aromatic amines
Amino Acids
Hydrazines
Sulfonamides

Products: Substrate + Acetyl group (CH3- CR=O)

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Glutathione conjugation

Target:
Enz:
Cofactor:
Product:

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Enzymes: Glutathione S-transferase (GST-Multiple isofoms)
Liver (cytosol & microsomal)

Cofactor: Glutathione (GSH)

Target functional group:
(any electrophilic group)
Halides
Epoxides
Other Electrophiles

Products:
Start with Michael acceptor alpha and beta unsaturated carbon end with cysteine.

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Catechol Methylation

Target:
Enz:
Cofactor:
Product:

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Enzymes:
-Catechol-O-Methyl transferace (COMT)
-liver (cytosol), kidney, Nervous
Tissue
Cofactor:
-S-adenosylmethionine (SAM)

Target functional group: Catechol (COMT) Catechols

Products: ether

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ulfate conjugation
Amino acid conjugation

Target:
Enz:
Cofactor:
Product:

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Enzymes:
-Acyl Synthetase (coenzyme A activation of target)

Cofactor:
-Glycine (or Glutamine)

Target functional group:
-Aromatic
-aliphatic
-heterocyclic carboxylic acids

Products: substrate + Glycine or glutamine bonded by amide bond. es

Front 31

List all phase 1 rxn using mnemonic

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HaNDED MAO FAXing XiO in ARKANSas

C450: Hydroxylation (aromat/aliph), NOS dealkylation, desaturation, epoxidation, dehalogenation

Others:
FMO
AD/ALD
MAO
XO

ARKANSas (reductions)
Aldehyde
dbl bonds
Ketone
AZO
Sulfoxide to sulfide

Hydrolysis
Ester and Amide

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List all phase 2 rxns using mnemonic

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all conjugative processes
Sulfate
N-Acetylation
Amino Acid
Glutathione
Methylation
Glucuronide

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mnemonic for phase II reactions

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SNAG the MG!

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Inducer(s) of:
CYP1

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cigarette smoke,
charred meats
omeprazole

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List the INHIBITORS of CYP450

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Grapefruit juice (especially 3A4)
Drugs w/sp2 hybridized nitrogen atoms (e.g., imidazole or pyridine)
Hydrophobic amines: metabolites bind to heme iron
Quindine (CYP2D6)
Protease inhibitors (e.g. ritonavir (CYP3A4))

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Inducer(s) of:
CYP2A,B,C

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Barbiturates (phenobarbitol)
Rifampin

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Inducer(s) of:
CYP2D

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No inducers known

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Inducer(s) of:
CYP2E

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Ethanol
Isoniazid

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Inducer(s) of:
CYP3A

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Barbiturates
Rifampin
Carbamazepine
St. John’s Wort
Efavirenz

Front 40

List the drug-metabolizing CYPs (P450s) that are inducible and know some of the compounds that induce them.

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CYP1 cigarette smoke, polycyclic aromatic hydrocarbons, charred meats, omeprazole

CYP2A,B,C Barbiturates (phenobarbitol), Rifampin

CYP2E Ethanol-Isoniazid

CYP3A Barbiturates: Rifampin, Carbamazepine, St. John’s Wort, Efavirenz


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adenine

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guanine

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cytosine

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thymine

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uracil

Front 46

Name this molecule

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Adenine