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Difference Between Phase I and Phase II Metabolism

January 6, 2019 Posted by Dr.Samanthi

The key difference between phase I and phase II metabolism is that the phase I metabolism converts a parent drug to polar active metabolites while phase II metabolism converts a parent drug to polar inactive metabolites.

Metabolism (drug metabolism) is the anabolic and catabolic breakdown of drugs by living organisms. Hence, drug metabolism is an important aspect of living systems. It occurs through enzymatic reactions. Furthermore, drug metabolism is of three phases; Phase I (modification), Phase II (conjugation) and Phase III (further modification and excretion) and all three phases actively involve to detoxify and remove xenobiotics from the cells.

CONTENTS

1. Overview and Key Difference
2. What is Phase I Metabolism
3. What is Phase II Metabolism
4. Similarities Between Phase I and Phase II Metabolism
5. Side by Side Comparison – Phase I vs Phase II Metabolism in Tabular Form
6. Summary

What is Phase I Metabolism?

Phase I reactions convert a parent drug to polar active metabolites through unmasking or insertion of a polar functional group. Therefore, in phase I drug metabolism, reactions occur through oxidation (cytochrome p450 monooxygenase system), reduction (NADPH cytochrome P450 reductase), hydrolysis (esterases), etc.

Here, a range of enzymes reacts to introduce polar reactive groups to the substrate (drug). Hence, it is the phase called modification. The most common modification is hydroxylation. It is catalyzed by cytochrome P-450 dependent mixed function oxidase system.

Difference Between Phase I and Phase II Metabolism

Figure 01: Phase I Metabolism

Moreover, the common oxidation reaction during phase I involves the conversion of a C-H bond into a C-OH bond. And, this is important since it converts a prodrug (pharmacologically inactive drug) to an active drug. Also, phase I metabolism can convert non-toxic molecule to a toxic molecule.  However, the drugs metabolized by phase I metabolism have longer half-lives.

What is Phase II Metabolism?

Phase II reactions convert a parent drug to polar inactive metabolites through conjugation of subgroups to -SH, -OH, -NH2 functional groups on the drug. Hence, phase II metabolism occurs via methylation (methyltransferase), acetylation (N-acetyltransferase), sulfation (sulphotransferase) and glucuronidation (UDP-glucuronosyltransferase).

Key Difference Between Phase I and Phase II Metabolism

Figure 02: Phase II Metabolism

The conjugated metabolites have increased molecular weight and become less active than the drug substrate. Therefore, these metabolic products are renally excreted. Individuals with deficient acetylation capacities suffer prolonged or toxic responses to normal drug doses due to low levels of metabolic rates.

What are the Similarities Between Phase I and Phase II Metabolism?

  • Both phases I and II metabolism involve drug anabolism and catabolism.
  • Also, both phases produce polar molecules.
  • And, they occur in living systems.

What is the Difference Between Phase I and Phase II Metabolism?

Phase I and phase II metabolism are two of the three phases of drug metabolism. Phase I metabolism converts a parent drug to polar active metabolites while phase II metabolism converts parent into polar inactive metabolites. Therefore, this is the key difference between phase I and phase II metabolism.  Furthermore, phase I metabolism occurs via unmasking or insertion of polar functional groups while phase II metabolism occurs via conjugation of subgroups. Hence, this is another difference between phase I and phase II metabolism.

Moreover, a further difference between phase I and phase II metabolism is that the reactions involving in phase I metabolism are oxidation, reduction and hydrolysis while the reactions involving in phase II metabolism are Methylation, glucuronidation, acetylation and sulfation.

The below infographic represents more details on the difference between phase I and phase II metabolism.

Difference Between Phase I and Phase II Metabolism in Tabular Form

Summary – Phase I vs Phase II Metabolism

Metabolism (drug metabolism) is the anabolic and catabolic breakdown of drugs by living organisms. The key difference between phase I and phase II metabolism is that the phase I reactions convert a parent drug to polar active metabolites through unmasking or insertion of  polar functional groups whilst phase II reactions convert a parent drug to polar inactive metabolites through conjugation of subgroups to -SH, -OH and -NH2 functional groups on the drug. Furthermore, the drugs metabolized by phase I metabolism have a longer half-life than that metabolized by phase II metabolism.

Reference:

1.“Phase I Drug Metabolism.” H2NC6H4CO2C2H5, Drugs. Available here  

Image Courtesy:

1.”Xenobiotic metabolism”By TimVickers – Own work, (Public Domain) via Commons Wikimedia
2.”Sulfotep metabolites”By Toxsulfotep – Own work, (CC BY-SA 3.0) via Commons Wikimedia

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Filed Under: Biochemistry

About the Author: Dr.Samanthi

Dr.Samanthi Udayangani holds a B.Sc. Degree in Plant Science, M.Sc. in Molecular and Applied Microbiology, and PhD in Applied Microbiology. Her research interests include Bio-fertilizers, Plant-Microbe Interactions, Molecular Microbiology, Soil Fungi, and Fungal Ecology.

Comments

  1. Steph Major says

    April 25, 2020 at 12:29 pm

    So helpful! Thank you.

    Reply

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