CYP Genes.

Cytochrome P450 Enzymes

The Phase I detox enzymes that metabolize most drugs and activate toxins for clearance.

What CYP enzymes do.

Cytochrome P450 (CYP) enzymes are the largest family of drug-metabolizing enzymes. They perform Phase I detoxification—adding reactive groups to fat-soluble compounds so Phase II can finish the job.

What they do

• Add -OH groups to toxins (oxidation)
• Metabolize 70-80% of all medications
• Activate prodrugs to their active forms
• Metabolize hormones, vitamins, fatty acids
• Process environmental chemicals

The catch

• Phase I can CREATE toxic intermediates
• Needs Phase II to complete detox
• Highly variable between individuals
• Affected by drugs, foods, supplements
• Can cause drug interactions

Metabolizer phenotypes.

Based on your CYP gene variants, you fall into one of these categories for each enzyme.

Poor Metabolizer (PM)

Little to no enzyme activity. Drugs accumulate, increasing side effect risk. Prodrugs (like codeine) don't work.

Intermediate Metabolizer (IM)

Reduced enzyme activity. May need dose adjustments. In between PM and normal.

Normal/Extensive Metabolizer (EM)

Standard enzyme activity. Standard drug doses typically appropriate.

Ultra-Rapid Metabolizer (UM)

Increased enzyme activity. Drugs clear too fast—may need higher doses. Prodrugs may convert too rapidly (dangerous with codeine).

Key CYP genes.

CYP1A2

Cytochrome P450 1A2

Metabolizes caffeine, some drugs, and environmental toxins

Variants: *1F variant associated with fast induction by smoking/charred meat

Impact: Determines if you're a fast or slow caffeine metabolizer. Fast metabolizers can drink coffee late; slow metabolizers get jitters.

CaffeineMelatoninTheophyllineSome antidepressantsPolycyclic aromatic hydrocarbons

CYP2D6

Cytochrome P450 2D6

Metabolizes ~25% of all medications

Variants: Highly polymorphic—from no function to ultra-rapid metabolism

Impact: Affects response to codeine, many antidepressants, tamoxifen, beta-blockers. Poor metabolizers may have adverse effects; ultra-rapid may need higher doses.

Codeine → morphineTramadolMany SSRIsTamoxifenBeta-blockers

CYP2C19

Cytochrome P450 2C19

Metabolizes proton pump inhibitors, clopidogrel, some antidepressants

Variants: *2 and *3 are loss-of-function; *17 is gain-of-function

Impact: Poor metabolizers may not activate clopidogrel (Plavix) properly—important for cardiac patients. Also affects PPI effectiveness.

Omeprazole/PPIsClopidogrel (Plavix)Some antidepressantsSome benzodiazepines

CYP2C9

Cytochrome P450 2C9

Metabolizes warfarin, NSAIDs, some diabetes drugs

Variants: *2 and *3 reduce enzyme activity

Impact: Poor metabolizers need lower warfarin doses—critical for preventing bleeding. Also affects NSAID metabolism.

WarfarinNSAIDsSulfonylureasLosartan

CYP3A4/CYP3A5

Cytochrome P450 3A4 and 3A5

Metabolizes ~50% of all medications—the most important drug-metabolizing enzyme

Variants: CYP3A5*3 is the most common non-expressor variant

Impact: Affects metabolism of statins, immunosuppressants, many cancer drugs. Inhibited by grapefruit juice.

StatinsCyclosporineMany cancer drugsCalcium channel blockersBenzodiazepines

CYP1B1

Cytochrome P450 1B1

Metabolizes estrogen (4-hydroxylation pathway) and activates procarcinogens

Variants: Leu432Val affects activity

Impact: Higher activity may produce more genotoxic estrogen metabolites. Relevant for hormone-sensitive cancers.

EstrogenEnvironmental procarcinogensSome drugs

The grapefruit effect.

Grapefruit inhibits CYP3A4 in the gut, causing drugs to accumulate. This is why so many medications warn against grapefruit juice.

CYP inhibitors and inducers:

Inhibitors (slow CYP)

• Grapefruit juice (CYP3A4)
• Turmeric/curcumin
• Many medications
• Some supplements

Inducers (speed up CYP)

• Cruciferous vegetables (CYP1A2)
• Charred meat (CYP1A2)
• Smoking (CYP1A2)
• St. John's Wort (CYP3A4)

"Always check for CYP interactions when starting new medications or supplements."

Reality Check

Genes don't act alone.

CYP doesn't determine your fate. It reveals where the system might need support.

Where it matters

CYP enzymes are concentrated in the liver but also present in the gut, lungs, skin, and other tissues. Gut CYP affects first-pass metabolism of oral drugs.

Expression depends on

• Nutrient availability
• Sunlight exposure
• Toxin burden
• Cell turnover rate
• Age and hormonal status

SNPs are throttles, not defects

Genetic variants often slow down pathways to protect the system from overwhelm. They reveal where you need to go slower, not that you're broken.

The real question

Not "what does this gene do?" but "what is this pathway already struggling with that makes this gene relevant?"

Related patterns

Slow Clearance

"Genes don't cause outcomes. They reveal where the system is already under pressure."

Pharmacogenomics in action.

CYP testing is one of the most clinically actionable genetic tests. Here's how it changes prescribing:

Codeine and CYP2D6

Codeine must be converted to morphine by CYP2D6. Poor metabolizers get no pain relief. Ultra-rapid metabolizers can overdose. The FDA requires genetic testing warnings.

Clopidogrel (Plavix) and CYP2C19

Clopidogrel is a prodrug activated by CYP2C19. Poor metabolizers have higher rates of heart attacks and stent thrombosis. Alternative drugs are available.

Warfarin and CYP2C9

CYP2C9 poor metabolizers need significantly lower warfarin doses. Testing can help find the right dose faster and prevent bleeding complications.

Antidepressants and CYP2D6/CYP2C19

Many antidepressants are metabolized by these enzymes. Testing can help predict who will have side effects or poor response.

Your CYP genes affect every medication you take.

Pharmacogenomic testing is one of the most actionable genetic tests available. Consider it before starting new medications.

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