Activities of Human Alcohol Dehydrogenases in The Metabolic Pathways of Ethanol and Serotonin
Activities of Human Alcohol Dehydrogenases in The Metabolic Pathways of Ethanol and Serotonin
Activities of Human Alcohol Dehydrogenases in The Metabolic Pathways of Ethanol and Serotonin
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https://www.ncbi.nlm.nih.gov/pubmed/10336614 1/3
2/7/2017 Activitiesofhumanalcoholdehydrogenasesinthemetabolicpathwaysofethanolandserotonin.PubMedNCBI
Format:Abstract Sendto
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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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