GST Genes.
Glutathione S-Transferases
The Phase II detox enzymes that conjugate toxins with glutathione for elimination.
What GST does.
GST enzymes are the workhorses of Phase II detoxification. They attach glutathione to toxins, making them water-soluble so your kidneys can excrete them.
GST functions:
- ✓Conjugates glutathione to toxins, making them water-soluble for excretion
- ✓Neutralizes reactive oxygen species and oxidative stress products
- ✓Metabolizes drugs and medications
- ✓Detoxifies environmental chemicals (smoke, pesticides, solvents)
- ✓Protects DNA from carcinogen damage
The deletion problem
Unlike most genes where variants reduce function, GSTM1 and GSTT1 can be completely deleted. If you have the "null" genotype, you make zero enzyme. This is surprisingly common.
The GST family.
GST is actually a family of related enzymes. Each has different substrate preferences and tissue distribution.
GSTM1
Glutathione S-Transferase Mu 1Detoxifies polycyclic aromatic hydrocarbons (smoke, exhaust), epoxides, and certain drugs
Key variant: Deletion (null) present in 40-60% of population
Impact: Complete loss of this enzyme's function; increased sensitivity to smoke and environmental toxins
GSTT1
Glutathione S-Transferase Theta 1Detoxifies industrial solvents, halogenated compounds, and oxidative stress products
Key variant: Deletion (null) present in 15-25% of Caucasians, higher in Asians
Impact: Loss of enzyme function; may affect response to certain chemotherapies
GSTP1
Glutathione S-Transferase Pi 1Expressed in most tissues; detoxifies carcinogens, drugs, and oxidative stress products
Key variant: Ile105Val (rs1695) - Val allele reduces activity
Impact: Most studied GST; affects drug metabolism and cancer risk in some studies
GSTA1
Glutathione S-Transferase Alpha 1Highly expressed in liver; detoxifies aflatoxins and oxidative stress
Key variant: Promoter variants affect expression levels
Impact: Important for liver detox capacity
Phase II in context.
Detoxification happens in three phases. GST is part of Phase II.
Phase I (CYP450)
Activates toxins by adding reactive groups. Makes fat-soluble toxins ready for conjugation. Can create MORE toxic intermediates.
Phase II (GST, etc.)
Conjugates reactive intermediates with glutathione, sulfate, or glucuronide. Makes them water-soluble and less toxic.
Phase III (Transport)
Exports conjugated toxins out of cells and into bile or urine for elimination. Requires functional transporters.
"Fast Phase I + Slow Phase II = Toxic intermediate accumulation. Balance matters."
Genes don't act alone.
GST doesn't determine your fate. It reveals where the system might need support.
Where it matters
Different GST enzymes dominate in different tissues. GSTP1 is widely expressed, GSTA1 is high in liver, GSTM1 matters for lung tissue.
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
"Genes don't cause outcomes. They reveal where the system is already under pressure."
Support strategies.
Support glutathione production
GST enzymes need glutathione to work. NAC, glycine, and glutamine are precursors. Whey protein provides cysteine.
Eat cruciferous vegetables
Sulforaphane (from broccoli sprouts) strongly induces GST expression. Other crucifers help too.
Reduce toxin exposure
With less GST capacity, minimizing exposure is more important. Filter water and air, avoid smoke, choose organic when possible.
Support Phase I and III too
Detox is a three-phase process. Phase I activates toxins, Phase II (GST) conjugates them, Phase III exports them. All must work together.
Consider liposomal glutathione
Direct glutathione supplementation can help, especially liposomal forms for better absorption.
Support with selenium
Selenium is needed for glutathione peroxidase, which works alongside GST in antioxidant defense.
Practical implications.
Smoke sensitivity
GSTM1 null individuals are more susceptible to lung damage from cigarette smoke. If you have this genotype, never smoke and avoid secondhand smoke.
Medication responses
GST variants affect metabolism of many drugs. GSTP1 variants can affect chemotherapy response. Always inform healthcare providers about genetic testing.
Cruciferous vegetables are medicine
Sulforaphane from broccoli sprouts can induce GST expression, potentially compensating for genetic variants. This is especially important for null genotypes.
Exercise induces GST
Regular exercise upregulates GST enzymes as part of the adaptive response to oxidative stress. Another reason exercise is protective.
GST variants mean work smarter, not just harder.
You can't change your genes, but you can reduce exposure, support glutathione, and induce enzyme expression through diet and lifestyle.