Activities of Human Alcohol Dehydrogenases in The Metabolic Pathways of Ethanol and Serotonin

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2/7/2017 Activitiesofhumanalcoholdehydrogenasesinthemetabolicpathwaysofethanolandserotonin.

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2/7/2017 Activitiesofhumanalcoholdehydrogenasesinthemetabolicpathwaysofethanolandserotonin.PubMedNCBI

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EurJBiochem.1999Jun262(2):3249.
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Activitiesofhumanalcoholdehydrogenasesinthemetabolic
pathwaysofethanolandserotonin.
SvenssonS1,SomeM,LundsjA,HelanderA,CronholmT,HgJO.

Authorinformation
1DepartmentofMedicalBiochemistry,KarolinskaInstitutet,Stockholm,Sweden.

Abstract
Alcoholsandaldehydesinthemetabolicpathwaysofethanolandserotoninare
substratesforalcoholdehydrogenases(ADH)ofclassIandII.Inadditiontothe
reversiblealcoholoxidation/aldehydereduction,theseenzymescatalysealdehyde
oxidation.ClassIgammagammaADHcatalysesthedismutationofbothacetaldehyde
and5hydroxyindole3acetaldehyde(5HIAL)intotheircorrespondingalcoholsand
carboxylicacids.Theturnoverofacetaldehydedismutationishigh(kcat=180min1)but
saturationisreachedfirstathighconcentrations(Km=30mm)whiledismutationof5
HIALissaturatedatlowerconcentrationsandistherebymoreefficient(Km=150
micromkcat=40min1).InasystemwhereNAD+isregenerated,theoxidationof5
hydroxytryptopholto5hydroxyindole3aceticacidproceedswithconcentrationlevelsof
theintermediary5HIALexpectedforatwostepoxidation.Butanaland5HIALoxidation
isalsoobservedforclassIADHinthepresenceofNADH.TheclassIIenzymeisless
efficientinaldehydeoxidation,andtheethanoloxidationactivityofthisenzymeis
competitivelyinhibitedbyacetate(Ki=12mm)and5hydroxyindole3aceticacid(Ki=2
mm).Reductionof5HIALisefficientlycatalysedbyclassIgammagammaADH(kcat=
400min1Km=33microm)inthepresenceofNADH.Thisindicatesthattheincreased
5hydroxytryptophol/5hydroxyindole3aceticacidratioobservedafterethanolintake
maybeduetotheincreasedNADH/NAD+ratioontheclassIADH.

PMID:10336614

[PubMedindexedforMEDLINE] Freefulltext

PublicationTypes,MeSHTerms,Substances
PublicationTypes
ResearchSupport,NonU.S.Gov't

MeSHTerms
AlcoholDehydrogenase/antagonists&inhibitors
AlcoholDehydrogenase/metabolism*
Aldehydes/metabolism
Ethanol/metabolism*
Humans
Hydrogen/metabolism
HydroxyindoleaceticAcid/metabolism
Hydroxytryptophol/metabolism
Kinetics
NAD/metabolism
OxidationReduction
Serotonin/metabolism*

https://www.ncbi.nlm.nih.gov/pubmed/10336614 2/3
2/7/2017 Activitiesofhumanalcoholdehydrogenasesinthemetabolicpathwaysofethanolandserotonin.PubMedNCBI

Substances
Aldehydes
NAD
Hydroxytryptophol
Serotonin
Ethanol
HydroxyindoleaceticAcid
Hydrogen
AlcoholDehydrogenase

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