The cytochrome P450 enzyme CYP2E1 occurs in many parts of the human body (skin, nose, heart, brain, lung, liver, kidney etc.), but is most concentrated in the human liver. It makes up only about 7% of the total P450 enzymes in the liver.[16]
CYP2E1 accounts for approximately 7% of total CYP450 in the human liver.
Many sulphur-containing agents block this enzyme, such as carbon disulphide, diethyldithiocarbamate, and disulfiram.[16]
Enzyme Actions
1'-Hydroxylation of Allylbenzenes
Unlike many other cytochrome P450 enzymes, CYP2E1 appears to only catalyze 1'-hydroxylation, without also catalyzing O-demethylation or O-demethylenation. For this reason, it could possibly be the single most important cytochrome P450 enzyme to induce to help achieve oilahuasca activation.
CYP2E1 and CYP1A2 can each catalyze the metabolism of methyl eugenol to 1'-hydroxymethyleugenol.
methyl eugenol | CYP2E1 + CYP1A2 | 1'-hydroxymethyleugenol |
---|---|---|
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CYP2E1, and to a lesser degree CYP2C9, can each catalyze the metabolism of safrole to 1'-hydroxysafrole.
safrole | CYP2E1 + CYP2C9 | 1'-hydroxysafrole |
---|---|---|
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—-> | ![]() |
The alcohol 1'-hydroxyestragole is proven to be created from the allylbenzene methyl chavicol in human liver in vitro primarily by the P450 enzymes CYP1A2, CYP2A6 and CYP2E1.[21][22]
methyl chavicol | CYP2E1 | 1'-hydroxyestragole |
---|---|---|
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Action on Ketones
CYP2E1 oxidizes several ketones include acetone, methyl ethyl ketone, and methyl isobutyl ketone.[16] Acetone is a potent inducer of CYP2E1.[16]
CYP2E1 is involved in the conversion of acetone to acetol in mice.[14]
acetone | CYP2E1 | acetol |
---|---|---|
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Creation of Aldehydes
CYP2E1 catalyzes the metabolism of ethanol to acetaldehyde. In this reaction, CYP2E1 initially forms a very unstable gem-diol, known as 1,1-ethanediol, which then condenses to form acetaldehyde.
Ethanol | CYP2E1 | 1,1-Ethanediol | Condensation | Acetaldehyde |
---|---|---|---|---|
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-> | ![]() |
-> | ![]() |
CYP2E1 catalyzes the metabolism of propargyl alcohol to propiolaldehyde.
propargyl alcohol | CYP2E1 | propiolaldehyde |
---|---|---|
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—-> | ![]() |
Oxygen Double Bond Creation
CYP2E1 catalyzes the metabolism of acetaminophen to N-acetyl-4-benzoquinoneimine.
acetaminophen | CYP2E1 | N-acetyl-4-benzoquinoneimine |
---|---|---|
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—-> | ![]() |
Epoxide Creation
CYP2E1 is involved in many epoxidation reactions. CYP2E1 epoxidates acrylamide into glycidamide[15], acrylonitrile into 2-cyanoethylene oxide, and benzene to benzene oxide. CYP2E1 and CYP1A2 together epoxidize styrene to styrene oxide. CYP2E1 together with CYP1A2 and CYP3A4 epoxidates trans-phenylpropylene (propenylbenzene) to it’s epoxide.
Inhibitors of CYP2E1
CYP2E1 is easily inhibited. Common foods such as garlic and watercress are proven to inhibit CYP2E1 in humans.
Potent Inhibitors | Strength | Dosage | Verified in Humans |
---|---|---|---|
Bergamot EO | ? | ? | ? |
Cinnamaldehyde | ? | ? | ? |
Cinnamon (contains o-methoxycinnamaldehyde) | ? | ? | ? |
Cinnamon EO1 | ? | 5-10 drops (Unverified) | ? |
Disulfiram [13] | ? | 500 mg | Yes |
Genistein [23] | ? | ? | ? |
Grapefruit EO | ? | ? | ? |
Kaempferol | 60–88% inhibition[27] | ? | ? |
Lemon EO | ? | ? | ? |
Lime EO | ? | ? | ? |
Neroli EO | ? | ? | ? |
O-methoxycinnamaldehyde[25] (found in cinnamon) | ? | ? | ? |
Orange EO | ? | ? | ? |
Petitgrain EO | ? | ? | ? |
Resveratrol | ? | 500 mg once daily for 10 days | Yes[26] |
Saint John’s Wort2 [8] | 100% | High doses | ? |
Star fruit juice | ? | ? | ? |
Tangerine EO | ? | ? | ? |
Tannic acid | ? | ? | ? |
Watercress | 56% increase in substrates | 50 grams of fresh watercress | Yes[20] |
Moderate Inhibitors | Strength | Dosage | Verified in Humans |
Moderate Inhibitors | ? | ? | ? |
Diallyl sulfide (found in garlic) | 31% inhibition | 0.2 mg/kg | Yes[19] |
Garlic EO [3] | 39% inhibition | ? | Yes[3] |
Horse Chestnut [8] 30% inhibition | 4.9 mM | ? | ? |
Kava [4] | 40% inhibition | ? | Yes[4] |
Mandarin EO | ? | ? | ? |
Piperine | Inhibition | 20 mg for 10 days | Yes[28] |
Safrole | ? | ? | ? |
Weak Inhibitors | Strength | Dosage | Verified in Humans |
Cone Flower [8] 10% inhibition | 4.7 mM | ? | ? |
Curcumin | ? | ? | ? |
Ginkgo biloba [8] | 20% inhibition | 2.2 mM | ? |
Valerian Root [8] 10% inhibition | 18.8 mM | ? | ? |
Myricetin | ? | ? | ? |
Sage [8] 10% inhibition | 8.2 mM | ? | ? |
Turmeric | ? | ? | ? |
Inhibitors of Unknown Potency | Strength | Dosage | Verified in Humans |
Acai berry oil | ? | ? | ? |
Bergamottin | ? | ? | ? |
Citral (geranial/neral) | ? | ? | ? |
Dimethyl sulfoxide (DMSO)3 | ? | ? | ? |
Ellagic Acid | ? | ? | ? |
Garlic | ? | ? | ? |
Lemongrass EO | ? | ? | ? |
Limonene | ? | ? | ? |
Naringin | ? | ? | ? |
Pomegranate juice [12] | ? | ? | In mice only |
Pomegranate leaf | ? | ? | ? |
Propylene glycol | ? | ? | ? |
Quercetin | ? | ? | ? |
Silymarin | ? | ? | ? |
In Vitro Inhibitors Ineffective in Humans | Strength | Dosage | Verified in Humans |
Goldenseal extract4 | No Effect[4] | ? | Yes |
White Grapefruit | No Effect[17] | 1-2 cups | Yes |
Inducers of CYP2E1
CYP2E1 appears to be easily and rapidly induced. In rats in vivo myristicin induced CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1. Maximum induction was at 12 hours for CYP2E1 and 24 hours for the other enzymes.[24] Glycerin showed a 250% to 300% increase of CYP2E1 in vitro after only 4-8 hours.[5]
Potent Inducers | Strength | Dosage | Verified in Humans |
---|---|---|---|
Acetone | ? | ? | Yes |
Alcohol [11] | 5-10x increase [16] | ? | Yes |
Glycerin [18][5] | 2.5x to 3x increase in vitro after 4-8 hours [5] | ? | ? |
Phenobarbital[9] | ? | ? | ? |
Saint John’s Wort5 | 30-65% Induction | 900mg | Yes |
Moderate Inducers | Strength | Dosage | Verified in Humans |
Rifampicin [8] | ? | ? | ? |
Inducers of Unknown Potency | Strength | Dosage | Verified in Humans |
Acetaldehyde [11] | ? | ? | ? |
Alpha-Naphthoflavone | ? | ? | ? |
Benzene [11] | ? | ? | ? |
1,3-Butandiol [11] | ? | ? | ? |
n-Butanol [11] | ? | ? | ? |
Capsaicin [2]6 | ? | ? | ? |
Cayenne pepper (contains Capsaicin)7 | ? | ? | ? |
Diethylether [11] | ? | ? | ? |
Dihidrocapsaicin [2] | ? | ? | ? |
Dimethyl sulfoxide (DMSO)8 | ? | ? | ? |
3-Hydroxypyridine [11] | ? | ? | ? |
Imidazole [11] | ? | ? | ? |
Isoniazid [11] | ? | ? | ? |
Isopropanol | ? | ? | ? |
Ketoconazole [11] | ? | ? | ? |
4-Methylpyrazole [11] | ? | ? | ? |
Myristicin | ? | ? | ? |
2-Propanol [11] | ? | ? | ? |
Pyridine | ? | ? | ? |
Pyrazine [11] | ? | ? | ? |
Pyrazole [11] | ? | ? | ? |
Pyrimidine [11] | ? | ? | ? |
Sage [6]9 | ? | ? | ? |
Skatole | ? | ? | ? |
Thiazole [11] | ? | ? | ? |
Thrichloroethylene [11] | ? | ? | ? |
Triazole [11] | ? | ? | ? |
Vanillin[1] | ? | ? | ? |
m-Xylene [11] | ? | ? | ? |
o-Xylene [11] | ? | ? | ? |
p-Xylene [11] | ? | ? | ? |
If an inducer or inhibitor is present on this page and reliable human in vivo studies are available but not shown on this page please leave a comment about it using the Discuss link at the bottom of this page so we can update the inhibitor's data.