Mastering Medical
USMLE Step 1 · Pharmacology

Phase I metabolism vs Phase II metabolism

How to tell Phase I metabolism and Phase II metabolism apart when a board question makes them look alike.

Fastest separator

Phase I modifies by oxidation/reduction/hydrolysis, often CYP-mediated; Phase II conjugates with glucuronide/sulfate/acetyl/methyl/glutathione groups.

Side by side

Phase I metabolismPhase II metabolism
Key clue

Oxidation, reduction, or hydrolysis, often through CYP enzymes, introduces or exposes a functional group.

Conjugation with glucuronide, sulfate, acetyl, methyl, amino acid, or glutathione groups to increase water solubility.

Mechanism

Phase I reactions chemically modify the drug and may activate, inactivate, or prepare it for conjugation.

Phase II reactions attach polar groups to promote renal or biliary elimination.

Labs and tests

CYP induction/inhibition, grapefruit-style interaction, or oxidation wording points Phase I.

Glucuronidation, acetylation, sulfation, or glutathione conjugation points Phase II.

The trap

A drug can go through both phases, so the reaction verb in the stem is the separator.

The repair move

Underline the metabolism verb: oxidize/reduce/hydrolyze means Phase I; conjugate means Phase II.

Try a free question

Core

A drug undergoes oxidation by cytochrome P450 enzymes, making it more polar and preparing it for further conjugation. Which metabolic phase is being described?

Show answer and explanation

Answer: A. Phase I metabolism. Phase I reactions include oxidation, reduction, and hydrolysis; cytochrome P450 oxidation is the classic clue.

Why the other choices are tempting

  • B. Phase II metabolism conjugates drugs with glucuronide, sulfate, acetyl, methyl, or glutathione groups.
  • C. Glomerular filtration is renal elimination, not hepatic biotransformation.
  • D. Enterohepatic recycling recirculates drug through bile and intestine.
  • E. Zero-order elimination describes saturated elimination kinetics.

Flashcards

Tap a card to flip it.

What is the fastest separator for Phase I metabolism vs Phase II metabolism?

Phase I modifies by oxidation/reduction/hydrolysis, often CYP-mediated; Phase II conjugates with glucuronide/sulfate/acetyl/methyl/glutathione groups.

What clue should make you choose Phase I metabolism?

Oxidation, reduction, or hydrolysis, often through CYP enzymes, introduces or exposes a functional group.

Quick answers

What is the fastest way to tell Phase I metabolism from Phase II metabolism?

Phase I modifies by oxidation/reduction/hydrolysis, often CYP-mediated; Phase II conjugates with glucuronide/sulfate/acetyl/methyl/glutathione groups.

What is the key clue for Phase I metabolism?

Oxidation, reduction, or hydrolysis, often through CYP enzymes, introduces or exposes a functional group.

What is the key clue for Phase II metabolism?

Conjugation with glucuronide, sulfate, acetyl, methyl, amino acid, or glutathione groups to increase water solubility.

What is the common trap with Phase I metabolism vs Phase II metabolism?

A drug can go through both phases, so the reaction verb in the stem is the separator.