Show Menu
Cheatography
  1. Home >
  2. Education >

Metabolism/Biotransformation Cheat Sheet (DRAFT) by

Phase 1 and phase 2 of metabolism.

This is a draft cheat sheet. It is a work in progress and is not finished yet.

Phae 1: Functi­ona­liz­ation reactions

Oxidative pathways
Reduction
Hydrolytic reactions
1. Alcohols & Aldehydes
1. Aldehydes
1. Esters
Ex: pyridoxine becoming pyridoxal
Become alcohols from H addition.
Ex: Cocaine, Aspirin, Mepiri­dine, Procaine
Aliphatic hydrox­yla­tion: addition of OH.
2. Azo-re­duction
The ester (COO) gp becomes an acid.
2. Oxidative N-deme­thy­lation
Ex: Sulfas­ala­zin­e--> Sulfap­yridine
2. Amides
Ex: Metham­phe­tamine, Lidocaine, Epinep­hrine
3. Nitror­edu­ction
Ex: Procai­namide
N with a CH3 (or other) get replaced by =O
Ex: Nitraz­epam, Chlora­mph­enicol
3. Glycosides
3. Oxidative deamin­ation
NO2 becomes NH2.
Ex: Digoxin --> Digoxin aglycone
Ex: Norepi­nep­hrine, Histamine, Mescaline
4. Dehalo­gen­ation
4. Epoxides
Removal of NH2 and its release as ammonia gas. Gets replaced by =O.
Ex: Halothane, Ethchl­ovynol
Ex: DES metabo­lit­e--> DES
4. Oxidative O-deal­kyl­ation
Ex: Phenac­etin, Codeine, Mescaline, Papaverine
O-alkyl becomes -OH.
5. N-Oxid­ation
Ex: Imipra­mine.
Coordinate bond between tert-N and O.
6. S-Oxid­ation
Ex: Chlorp­rom­azine; S-O (sulfo­xide) then becomes (S=O) Sulfone.
7. Desulf­uration
Ex: Thioba­rbital, Parathion
=S is replaced by =O
8. Epoxid­ation
Ex: DES; O in a strained tricyclic structure.

Phase 1: Functi­ona­lis­ation cont.

Decarb­oxy­lation
Oxidative pathways catalysed by other oxidoreductases
Reductive pathways by oxidor­edu­ctases
Ex: Histidine, a-meth­yldopa, L-Dopa.
Alcohol dehydr­oge­nases
Less signif­icant
Removal of carboxylic acid.
1ry alcohol (benzy­lal­cohol, phenet­hanol, retino­l)-­-> Aldehydes
Include reactions on:
Histid­ine­--> Histamine; L-Dopa­--> dopamine.
2ry alcoho­ls-­--> Ketones
1) C=O compounds 2) Olefins 3) Dehalo­gen­ation 4) other atoms
 
3ry alcohols do not react.
Hydrolytic pathways
 
Aldehyde dehydr­oge­nases
include hydrolyses enzymes
 
Aldehy­des­--> Acid
They add a water to functional groups.
 
Monoamine oxidase (MAO)
 
Has 2 forms/­iso­zymes A & B, that deaminate catech­ola­mines.
 
Treats Parkin­son's (esp MAO B).

Phase 2: conjug­ation reaction

Methyl­ation
Acetyl­ation & Acylation
Amino acid conjug­ation reactions
A methyl group on carrier (SAM) adds the methyl to O/N/S on the drug or phase 1 metabo­lite.
Acyl-c­oenzyme A is required
Glycine is used to conjugate COOH gp in xenobi­otics.
O-meth­ylation by COMT.
Ex: Sulfam­eth­oxazole where COCH3 gp is added.
Carrier is glycine N-acyl­tra­nsf­erase.
N-meth­ylation by N-meth­ylt­ran­sfe­rase.
Some people are fast or slow acetyl­ators and thus drug dose metabo­lized here should be adjusted.
S-meth­ylation by thiol or thiopurine methyl­tra­nsf­erases.
Thiol containing drugs (capto­pril, mercap­top­urine, propyl­thi­our­acil) are subjected to S-meth­yla­tion.
Captopril is unique in that phase 2 S-meth­ylation occurs first, then phase 1.

Phase 2: conjug­ation reaction cont.

Glucuronidation
Sulfate conjug­ation
Glutat­hione (GSH) conjug­ation
Miscel­laneous conjug­ation reactions
Conjug­ation with glucuronic acid with carrier UDPG.
A sulfate molecule is transf­erred from carrier, PAPS, to the substr­ate­/drug by enzyme cytosolic sulfot­ran­sfe­rases.
In its reduced form, its the tripeptide GSH. But it becomes in the oxidized form GS-SG and the SG attachs to drug
1) Phosph­ory­lation via phosph­otr­ans­ferase
The enzyme, UDP-gl­uco­uro­nosyl transf­erase, acts on O, N, S in the compound.
    
Ex: Zidovu­dine.
     
2) Endogenous carbonyl + Exogenous drug with hydrazines or hydraz­ide­s--­-> Hydraz­ones.