Handbook of Neurochemistry and Molecular Neurobiology (Amino Acids and Peptides in the Nervous System)

373 Pages·2007·4.09 MB·English

by  Simo S. Oja

Handbook of Neurochemistry and Molecular Neurobiology
AminoAcidsandPeptidesintheNervousSystem
Abel Lajtha (Ed.)
Handbook of
Neurochemistry and
Molecular Neurobiology
Amino Acids and Peptides in the
Nervous System
Simo S. Oja, Pirjo Saransaari and Arne Schousboe
With58 Figuresand 23Tables
Editor
AbelLajtha
Director
CenterforNeurochemistry
NathanS.KlineInstituteforPsychiatricResearch
140OldOrangeburgRoad
Orangeburg
NewYork,10962
USA
VolumeEditors
Prof.SimoS.Oja Prof.ArneSchousboe
TheCentreforLaboratoryMedicine Inst.forPharmacology
TampereUniversityHospital RoyalDanishSchoolofPharmacy
PB2000 Universitetsparken2
FI‐33520Tampere DK‐2100Copenhagen
Finland Denmark
E‐mail:Simo.Oja@uta.fi E‐mail:[email protected]
Prof.PirjoSaransaari
BrainResearchCenter
MedicalSchool
FI‐33014UniversityofTampere
Finland
E‐mail:pirjo.saransaari@uta.fi
LibraryofCongressControlNumber:2006922553
ISBN:978‐0‐387‐30342‐0
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TheelectronicversionofthewholesetwillbeavailableunderISBN:978‐0‐387‐30426‐7
TheprintandelectronicbundleofthewholesetwillbeavailableunderISBN:978‐0‐387‐35478‐1
(cid:1)2007SpringerScienceþBusinessMedia,LLC.
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Preface
Thisvolumedealswiththeroleofaminoacidsandsmallpeptidesinthecentralnervoussystem(CNS).The
variouschaptersdescribeindividuallythemetabolismandfunctionsofthedifferentcompounds.Amino
acidsareessentialbuildingblocksofproteinsbuttheyservealsootherimportantfunctionsintheCNS,for
instance,asneurotransmittersorneuromodulatorsintheirownrightorasprecursorsforneurotransmit-
ters.Theneurotransmitteractionsaremostlydescribedinothervolumesofthishandbook,asthearticlesin
this volume emphasize the other roles of amino acids in brain intermediary metabolism. For instance,
glutamateandg-aminobutyricacid(GABA)constitutetogetherwithglutamineandalanineanimportant
metabolic cluster involved in brain ammonia homeostasis. Glycine and serine are closely metabolically
intertwined.Histidineistheparentmoleculeforhistaminewithlesslimiteddistributioninnervoustissue.
Aromaticaminoacidsarelikewiseneurotransmitterprecursors,andtheirnormalconcentrationsessential
forhealthybraindevelopmentandfunctions.D-Aminoacidsaremorerecentlyrecognizedcompoundsof
significance.Thepreciseroleoftaurineisstillsomewhatobscure.Itisnotbrokendownintheorganismbut
hasbeenpostulatedtofunctionincellvolumeregulation,togetherwithotheraminoacidsandorganicand
inorganicelements.Ithasalsobeensuggestedtobeaninhibitoryneuromodulator.Arginine,citrulline,and
ornithineareconstituentsoftheureacycle,whichintheliverisimportantintheeliminationofammonia.
However, this cycle is not operating in the brain, and therefore ammonia accumulation is a significant
factor in the development of encephalopathy upon failure of liver functions (hepatic encephalopathy).
Disturbancesintheureacyclearelifethreateningforaffectedindividuals.Soarealsothedisturbancesinthe
metabolismofaromaticandbranched-chainaliphaticaminoacids.Inbornerrorsinaminoacidmetabo-
lismaregenerallynotcommonbuttheyalwaysresultinseverediseases.Agreatnumberofsmall-molecular
oligopeptideshavebeendetectedinbraintissue.Theirfunctionsandsignificancearestilllargelyunknown,
exceptincaseofN-acetylaspartateandglutathione.
Theeditorsthanktheauthorsfortheirsincereeffortstoproduceindividualup-to-datearticlesinthis
volume.Wethinkthatthisvolumewellcoversthemostimportantaspectsofmetabolismandfunctionsof
aminoacidsandsmallpeptidesintheCNS.Wehopethatthereaderswillshareouropinion.
SimoS.Oja
PirjoSaransaari
ArneSchousboe
Table of Contents
Preface .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. .. v
Contributors.. . .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. . ix
1 Glutamine,Glutamate,andGABA:MetabolicAspects .. .. .. . .. .. .. . .. .. .. 1
H.S.Waagepetersen.U.Sonnewald.A.Schousboe
2 Serine,Glycine,andThreonine . . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. . 23
T.J.deKoning.S.A.Fuchs.L.W.J.Klomp
3 Histidine .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. . 47
P.Panula
4 AromaticAminoAcidsintheBrain . .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. . 59
M.Cansev.R.J.Wurtman
5 Arginine,Citrulline,andOrnithine . .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. . 99
H.Wiesinger
6 BranchedChainAminoAcids(BCAAs)inBrain. .. . .. .. .. .. . .. .. .. . .. .. 117
S.M.Hutson.A.J.Sweatt.K.F.LaNoue
7 Sulfur‐ContainingAminoAcids . . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 133
G.J.McBean
8 Taurine . .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 155
S.S.Oja.P.Saransaari
9 NeurobiologyofD‐AminoAcids . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 207
E.Dumin.H.Wolosker
10 AminoAcidsandBrainVolumeRegulation:Contribution
andMechanisms . .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 225
H.Pasantes‐Morales
11 UreaCycleEnzymopathies .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 249
R.Butterworth
#Springer-VerlagBerlinHeidelberg2007
viii TableofContents
12 AmmoniaToxicityintheCentralNervousSystem . .. .. .. .. . .. .. .. . .. .. 261
J.Albrecht
13 DisordersofAminoAcidMetabolism . .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 277
M.Yudkoff
14 N‐AcetylaspartateandN‐Acetylaspartylglutamate. .. .. .. .. . .. .. .. . .. .. 305
M.H.Baslow
15 GlutathioneintheNervousSystem:RolesinNeuralFunctionandHealth
andImplicationsforNeurologicalDisease .. .. .. . .. .. .. .. . .. .. .. . .. .. 347
R.Jana´ky.R.Cruz‐Aguado.S.S.Oja.C.A.Shaw
16 LowMolecularWeightPeptides . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 401
K.L.Reichelt
Index . .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. . .. .. .. .. . .. .. .. . .. .. 413
Contributors
J.Albrecht S.M.Hutson
DepartmentofNeurotoxicology,M.Mossakowski WakeForestUniversitySchoolofMedicine,
MedicalResearchCentre,PolishAcademyofSciences, Winston-Salem,NC27157andDepartment
Pawin´skiegoSt.5,02‐106Warsaw,Poland ofBiochemistry,WakeForestUniversitySchool
ofMedicine,MedicalCenterBoulevard,
M.H.Baslow Winston-Salem,NC27157,USA
NathanS.KlineInstituteforPsychiatricResearch,Center
forNeurochemistry,140OldOrangeburgRoad, R.Jana´ky
Orangeburg,NewYork10962,USA DepartmentofPhysiology,UniversityofTampere
MedicalSchool,FIN‐33014,Tampere,Finland
R.Butterworth
NeuroscienceResearchUnit,HoˆpitalSaint-Luc(CHUM), L.W.J.Klomp
Montre´al,Que,Canada DepartmentofMetabolicDiseasesandtheLaboratory
forMetabolicDiseasesandEndocrinology,University
M.Cansev MedicalCentreUtrecht,TheNetherlands
DepartmentofBrainandCognitiveSciences,
MassachusettsInstituteofTechnology,CambridgeMA, K.F.LaNoue
02139,USAandDepartmentofPharmacologyand PennStateCollegeofMedicine,Hershey,PA17033,USA
ClinicalPharmacology,UludagUniversityMedical
School,Gorukle,Bursa,16059,Turkey G.J.McBean
DepartmentofBiochemistry,ConwayInstituteof
R.Cruz-Aguado BiomolecularandBiomedicalResearch,University
DepartmentofOphthalmology,Physiology,and CollegeDublin,Belfield,Dublin4,Ireland
ExperimentalMedicineandNeuroscienceProgram,
UniversityofBritishColumbia,Vancouver,British S.S.Oja
Columbia,Canada CentreforLaboratoryMedicine,TampereUniversity
Hospital,Tampere,Finland
T.J.deKoning
DepartmentofMetabolicDiseasesandtheLaboratory P.Panula
forMetabolicDiseasesandEndocrinology,University NeuroscienceCenter,InstituteofBiomedicine,POB63
MedicalCentreUtrecht,TheNetherlands (Haartmaninkatu8),FI‐00014,UniversityofHelsinki,
Finland
E.Dumin
DepartmentofBiochemistry,B.RappaportFacultyof H.Pasantes-Morales
Medicine,Technion-IsraelInstituteofTechnology,Haifa DepartmentofBiophysics,InstituteofCellPhysiology,
31096,Israel NationalUniversityofMexico,UNAM,MexicoCity,
Mexico
S.A.Fuchs
DepartmentofMetabolicDiseasesandtheLaboratory P.Saransaari
forMetabolicDiseasesandEndocrinology,University BrainResearchCenter,TampereUniversity
MedicalCentreUtrecht,TheNetherlands MedicalSchool,Tampere,Finland
#Springer-VerlagBerlinHeidelberg2007
x Contributors
A.Schousboe H.Wiesinger
DepartmentofPharmacologyandPharmacotherapy, Physiologisch-chemischesInstitut,Universita¨t
DanishUniversityofPharmaceuticalSciences, Tu¨bingen,Hoppe-Seyler-Str.4,D‐72076Tu¨bingen,
DK‐2100Copenhagen,Denmark Germany
C.A.Shaw H.Wolosker
DepartmentofOphthalmology,Physiology, DepartmentofBiochemistry,B.RappaportFacultyof
andExperimentalMedicineandNeuroscience Medicine,Technion-IsraelInstituteofTechnology,
Program,UniversityofBritishColumbia, Haifa31096,Israel
ResearchPavilion828W.10thAve.Vancouver,
BritishColumbia,V5Z1L8,Canada R.J.Wurtman
DepartmentofPharmacologyandClinical
U.Sonnewald Pharmacology,UludagUniversityMedicalSchool,
DepartmentofNeuroscience,NorwegianUniversity Gorukle,Bursa,16059,Turkey
ofScienceandTechnology(NTNU),
N‐7489Trondheim,Norway M.Yudkoff
DepartmentofPediatrics,UniversityofPennsylvania
A.J.Sweatt SchoolofMedicine,Children’sHospitalofPhiladelphia,
WakeForestUniversitySchoolofMedicine, 34thStreet&CivicCenterBoulevard,Philadelphia,
Winston-Salem,NC27157,USA PA19104,USA
H.S.Waagepetersen
DepartmentofPharmacologyandPharmacotherapy,
DanishUniversityofPharmaceuticalSciences,
DK‐2100Copenhagen,Denmark
1 Glutamine, Glutamate, and GABA:
Metabolic Aspects
H. S. Waagepetersen . U. Sonnewald . A. Schousboe
1 Introduction ...................................................................................... 2
2 Content ofGlutamate, Glutamine, and GABAinDifferentBrainRegions .................... 2
3 Metabolic Compartmentation at theMulticellular Level ....................................... 3
4 GABAand Glutamate Homeostasis ............................................................. 3
4.1 Glutamate ........................................................................................... 3
4.2 GABA ................................................................................................ 4
4.3 GABA–Glutamate–Glutamine Cycle ................................................................ 5
4.3.1 Glutamine ........................................................................................... 5
4.3.2 Ammonia Homeostasis intheGlutamate–Glutamine Cycle ...................................... 8
4.4 Alternative Glutamate Precursors .................................................................. 9
4.5 Ammonia Toxicity .................................................................................. 9
5 Glutamate‐Metabolizing Enzymes .............................................................. 10
5.1 Glutamate Dehydrogenase ......................................................................... 10
5.2 Aminotransferases .................................................................................. 10
5.3 Aminotransferase Versus GDH .................................................................... 11
6 Anaplerosis ...................................................................................... 11
6.1 PyruvateCarboxylase .............................................................................. 11
7 EnzymesInvolvedin Glutamine Metabolism ................................................... 12
7.1 Glutamine Synthetase .............................................................................. 12
7.2 Phosphate‐ActivatedGlutaminase ................................................................. 12
8 EnzymesInvolvedin GABA Metabolism ....................................................... 13
8.1 Glutamate Decarboxylase .......................................................................... 13
8.2 GABAaminotransferase ............................................................................ 13
9 Metabolic Compartmentation at theSingle‐CellLevel ......................................... 14
#Springer-VerlagBerlinHeidelberg2007