CYP2E1

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.[15]

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.[15]


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
methyl-eugenol.gif —-> 1-Hydroxymethyleugenol.png

CYP2E1, and to a lesser degree CYP2C9, can each catalyze the metabolism of safrole to 1'-hydroxysafrole.

safrole CYP2E1 + CYP2C9 1'-hydroxysafrole
safrole.gif —-> 1-hydroxysafrole.png

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.[20][21]

methyl chavicol CYP2E1 1'-hydroxyestragole
methyl_chavicol.png —-> 1-hydroxyestragole.png

Action on Ketones

CYP2E1 oxidizes several ketones include acetone, methyl ethyl ketone, and methyl isobutyl ketone.[15] Acetone is a potent inducer of CYP2E1.[15]

CYP2E1 is involved in the conversion of acetone to acetol in mice.[13]

acetone CYP2E1 acetol
acetone.png —-> acetol.png

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
Ethanol.png -> 1_1-Ethanediol.png -> Acetaldehyde.png

CYP2E1 catalyzes the metabolism of propargyl alcohol to propiolaldehyde.

propargyl alcohol CYP2E1 propiolaldehyde
propargyl-alcohol.png —-> propiolaldehyde.png

Oxygen Double Bond Creation

CYP2E1 catalyzes the metabolism of acetaminophen to N-acetyl-4-benzoquinoneimine.

acetaminophen CYP2E1 N-acetyl-4-benzoquinoneimine
Acetaminophen.png —-> N-acetyl-4-benzoquinoneimine.png

Epoxide Creation

CYP2E1 is involved in many epoxidation reactions. CYP2E1 epoxidates acrylamide into glycidamide[14], 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 [12] ? 500 mg Yes
Genistein [22] ? ? ?
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 [7] 100% High doses ?
Star fruit juice ? ? ?
Tangerine EO ? ? ?
Tannic acid ? ? ?
Watercress 56% increase in substrates 50 grams of fresh watercress Yes[19]
Moderate Inhibitors Strength Dosage Verified in Humans
Moderate Inhibitors ? ? ?
Diallyl sulfide (found in garlic) 31% inhibition 0.2 mg/kg Yes[18]
Garlic EO [2] 39% inhibition ? Yes[2]
Horse Chestnut [7] 30% inhibition 4.9 mM ? ?
Kava [3] 40% inhibition ? Yes[3]
Mandarin EO ? ? ?
Piperine Inhibition 20 mg for 10 days Yes[28]
Safrole ? ? ?
Weak Inhibitors Strength Dosage Verified in Humans
Cone Flower [7] 10% inhibition 4.7 mM ? ?
Curcumin ? ? ?
Ginkgo biloba [7] 20% inhibition 2.2 mM ?
Valerian Root [7] 10% inhibition 18.8 mM ? ?
Myricetin ? ? ?
Sage [7] 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 [11] ? ? In mice only
Pomegranate leaf ? ? ?
Propylene glycol ? ? ?
Quercetin ? ? ?
Silymarin ? ? ?
In Vitro Inhibitors Ineffective in Humans Strength Dosage Verified in Humans
Goldenseal extract4 No Effect[3] ? Yes
White Grapefruit No Effect[16] 1-2 cups Yes

Note: Piperine was previously in this list because it was shown to inhibit CYP2E1 by 30% in rats[6], however it was removed because another test using human liver found that piperine has almost no effect on CYP2E1.[23]


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.[4]

Potent Inducers Strength Dosage Verified in Humans
Acetone ? ? Yes
Alcohol [10] 5-10x increase [15] ? Yes
Glycerin [17][4] 2.5x to 3x increase in vitro after 4-8 hours [4] ? ?
Phenobarbital[8] ? ? ?
Saint John’s Wort5 30-65% Induction 900mg Yes
Moderate Inducers Strength Dosage Verified in Humans
Rifampicin [7] ? ? ?
Inducers of Unknown Potency Strength Dosage Verified in Humans
Acetaldehyde [10] ? ? ?
Alpha-Naphthoflavone ? ? ?
Benzene [10] ? ? ?
1,3-Butandiol [10] ? ? ?
n-Butanol [10] ? ? ?
Capsaicin [1]6 ? ? ?
Cayenne pepper (contains Capsaicin)7 ? ? ?
Diethylether [10] ? ? ?
Dihidrocapsaicin [1] ? ? ?
Dimethyl sulfoxide (DMSO)8 ? ? ?
3-Hydroxypyridine [10] ? ? ?
Imidazole [10] ? ? ?
Isoniazid [10] ? ? ?
Isopropanol ? ? ?
Ketoconazole [10] ? ? ?
4-Methylpyrazole [10] ? ? ?
Myristicin ? ? ?
2-Propanol [10] ? ? ?
Pyridine ? ? ?
Pyrazine [10] ? ? ?
Pyrazole [10] ? ? ?
Pyrimidine [10] ? ? ?
Sage [5]9 ? ? ?
Skatole ? ? ?
Thiazole [10] ? ? ?
Thrichloroethylene [10] ? ? ?
Triazole [10] ? ? ?
m-Xylene [10] ? ? ?
o-Xylene [10] ? ? ?
p-Xylene [10] ? ? ?
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