Human CYP2A6 K476E experimental variant: molecular mechanisms & dependencies

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation.
Human CYP2A6 K476E experimental variant → Coumarin 7-hydroxylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"}
experimental_model
Random mutagenesis of recombinant human CYP2A6
exposure
Wild-type enzyme and selected activity-reducing mutants
limitations
Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human engineered protein
plain_language
Adding more partner enzyme did not fully repair this variant.
primary_references
[coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
tissue_or_cell_type
Reconstituted enzyme system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 618–629
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Random mutagenesis of recombinant human CYP2A6 · source_derived_draft · unverified_draft
### coumarin-k476e-hydroxylation K476E reduced NADPH oxidation and ferric-enzyme reduction; excess reductase did not restore wild-type coumarin hydroxylation. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding more partner enzyme did not fully repair this variant. organism: Human engineered protein tissue_or_cell_type: Reconstituted enzyme system experimental_model: Random mutagenesis of recombinant human CYP2A6 limitations: Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested. exposure: Wild-type enzyme and selected activity-reducing mutants evidence_span: {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"} [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
Complete structured claim and evidence
CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity.
Human CYP2A6 K476E experimental variant → NADPH-cytochrome P450 oxidoreductase / POR source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"}
experimental_model
Random mutagenesis of recombinant human CYP2A6
exposure
Wild-type enzyme and selected activity-reducing mutants
limitations
Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested.
nutrient_topic
Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin
organism
Human engineered protein
plain_language
A protein change weakened its connection to the electron donor.
primary_references
[coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
tissue_or_cell_type
Reconstituted enzyme system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 605–616
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Random mutagenesis of recombinant human CYP2A6 · source_derived_draft · unverified_draft
### coumarin-k476e-por CYP2A6 K476E had lower affinity for NADPH-P450 reductase, contributing to reduced catalytic activity. Condition category: machinery_impairment nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein change weakened its connection to the electron donor. organism: Human engineered protein tissue_or_cell_type: Reconstituted enzyme system experimental_model: Random mutagenesis of recombinant human CYP2A6 limitations: Engineered protein dysfunction is not nutrient deficiency; no rescue by nutritional supplementation was tested. exposure: Wild-type enzyme and selected activity-reducing mutants evidence_span: {"source_cache": "artifacts/coumarin-research/16207711.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7", "start_char": 0, "end_char": 1740, "text_sha256": "a5f0bef9ac62d55ff5725e8c5cb4eca3e76ef715c758654e76c0c596c52ceab7"} [coumarin-p16207711] Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. (2005). https://pubmed.ncbi.nlm.nih.gov/16207711/ DOI: 10.1074/jbc.m508171200
Complete structured claim and evidence

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

Human CYP2A6 K476E experimental variant