精氨酸生素ppt

• • • • • • • • • • • • • NAGNAGP5CSCPS-­‐1NAGNAGNAG  NAGNCGNCGNAG  --• • 2ADP+PiCO2+NH3+H2O2ATPCPS-NAGNO  NOS  nNOS—  iNOS—  eNOS—m-­‐TORTLR4  NF  k  BNO-­‐HSP70  NO-­‐VEGFPPARγFig.  1.  Angiogenesis  and  vasculogenesis  forming  vessels:  (A)  angiogenesis:  it  occurs  iniNally  with  the  formaNon  of  the  budding  (1)  or  endothelial  cell  outgrowth  followed  by  stretching  (2)  of  small  vessels  and  branching  by  proliferaNon  (3)  of  exisNng  endothelial  cells  and  remodeling  (4);  (B)  vasculogenesis:  it  is  the  growth  of  capillaries  from  pre-­‐exisNng  vessels  (1  and  2),  aYer  formaNon  of  vascular  (capillary)  tubes,  these  undifferenNated  vessels  fuse  forming  a  conNnuous  vascular  structure  (3  and  4).  • • • • • • • • • • • mmol/lWu1996• Wu2004• • Kim  SW  &  Wu  G  (2004)  J  Nutr  134:  625-­‐630  Yao  K  et  al.  (2008)  138:  867-­‐872  NO    mTOR                • • • • • ((’&’&((&&&4&(&4&&4&￿1￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿!￿￿￿#$%￿￿￿#&’()*+%￿*,-.%￿/0$%￿12%￿34’2%5￿￿￿#-6789:￿-6;￿-=?￿￿￿@ABC()A&￿D￿￿￿EFG￿HI￿￿#JK￿.LM￿NO.￿￿￿JK￿PQR￿￿￿JKSTUVPMW￿X%￿￿￿Y5￿￿￿#RZ[\￿]^_‘￿ab[\cb?￿￿￿defgh]i￿9:￿￿￿?_‘jk_:￿lemn()￿￿￿op￿q￿￿￿r￿q￿￿s!tu‘&’STvwxy‘5￿￿￿zp(){|/￿￿}izp~￿￿￿￿￿￿￿￿￿$%&’￿￿3￿￿￿34-6￿/￿34/0ST3￿/0￿￿￿5￿￿￿￿/￿￿/0i:()￿￿￿￿￿/0￿￿￿￿￿￿￿￿￿￿￿￿2￿5￿￿*￿￿￿￿Wu￿Meininger(2000￿2002)￿Flynn￿(2002)￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿!￿￿￿!￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿#￿￿￿￿￿￿￿￿￿￿￿￿￿$%￿￿￿￿￿￿￿￿￿￿￿￿￿%￿￿￿￿￿￿￿￿￿￿￿￿￿&￿￿￿￿￿￿￿￿￿￿￿￿￿’￿￿￿￿￿￿￿￿￿￿￿￿￿(￿￿￿￿￿￿￿￿￿￿￿￿￿￿)￿￿￿￿￿￿￿￿￿￿￿￿￿*￿￿￿￿￿￿￿￿￿￿￿￿￿+￿￿￿￿￿￿￿￿￿￿￿￿￿,￿￿￿￿￿￿￿￿￿￿￿￿￿-￿￿￿￿￿￿￿￿￿￿￿￿￿.￿￿￿￿￿￿￿￿￿￿￿￿￿/0￿￿￿￿￿￿￿￿￿￿￿￿123￿456789:;￿￿￿￿￿￿￿=￿?@AB/CDE@￿!!((’&’&((&&&4&(&4&&4&￿1￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿!￿￿￿#$%￿￿￿#&’()*+%￿*,-.%￿/0$%￿12%￿34’2%5￿￿￿#-6789:￿-6;￿-=?￿￿￿@ABC()A&￿D￿￿￿EFG￿HI￿￿#JK￿.LM￿NO.￿￿￿JK￿PQR￿￿￿JKSTUVPMW￿X%￿￿￿Y5￿￿￿#RZ[\￿]^_‘￿ab[\cb?￿￿￿defgh]i￿9:￿￿￿?_‘jk_:￿lemn()￿￿￿op￿q￿￿￿r￿q￿￿s!tu‘&’STvwxy‘5￿￿￿zp(){|/￿￿}izp~￿￿￿￿￿￿￿￿￿$%&’￿￿3￿￿￿34-6￿/￿34/0ST3￿/0￿￿￿5￿￿￿￿/￿￿/0i:()￿￿￿￿￿/0￿￿￿￿￿￿￿￿￿￿￿￿2￿5￿￿*￿￿￿￿Wu￿Meininger(2000￿2002)￿Flynn￿(2002)￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿!￿￿￿!￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿￿#￿￿￿￿￿￿￿￿￿￿￿￿￿$%￿￿￿￿￿￿￿￿￿￿￿￿￿%￿￿￿￿￿￿￿￿￿￿￿￿￿&￿￿￿￿￿￿￿￿￿￿￿￿￿’￿￿￿￿￿￿￿￿￿￿￿￿￿(￿￿￿￿￿￿￿￿￿￿￿￿￿￿)￿￿￿￿￿￿￿￿￿￿￿￿￿*￿￿￿￿￿￿￿￿￿￿￿￿￿+￿￿￿￿￿￿￿￿￿￿￿￿￿,￿￿￿￿￿￿￿￿￿￿￿￿￿-￿￿￿￿￿￿￿￿￿￿￿￿￿.￿￿￿￿￿￿￿￿￿￿￿￿￿/0￿￿￿￿￿￿￿￿￿￿￿￿123￿456789:;￿￿￿￿￿￿￿=￿?@AB/CDE@￿!!• 12-­‐5-­‐• • • • • previouslyidentifiedbutmayresultfromdecreasesincellularactivitiesofbothP5CsynthaseandNAGsynthase.Thisintriguingfindingalsoraisedanimportantquestionofwhetherarginineisinsufficientforsupportingthemetabolicneedsof7-to21-d-oldsow-rearedpiglets(16,21).Argininedeficiencyinsow-rearedpigletsBecauseofthepracticallimitationinconductinganitro-gen-balancestudywithsow-rearedpiglets,wedecidedtomea-sureplasmabiochemicalvariables(e.g.,arginine,ammonia,andnitriteplusnitrate,stableoxidationproductsofNO)asindicatorsofargininestatusinpiglets(33).Therationalewasasfollows:1)arginineplaysacrucialroleinammoniadetox-ificationviathehepaticureacycleandisthephysiologicalsubstrateforNOsynthesis(30);2)adecreaseinplasmaarginineconcentrationsandanincreaseinplasmaammonialevelsaresensitiveindicatorsofargininedeficiencyinneo-nates,includingpiglets(2,9);and3)plasmaconcentrationsofnitriteplusnitratereflecttheavailabilityofarginineforsup-portingsystemicNOsynthesisinneonates(34).Ourresultsshowedthatplasmalevelsofmostaminoacidsdidnotchangeinpigletsduringthesucklingperiod(33),suggestingthatmechanismsexistformaintainingtheirho-meostasis.However,plasmaconcentrationsofarginineanditsimmediateprecursors(ornithineandcitrulline)decreasedpro-gressivelyby20–41%,withincreasingpostnatalagefrom3to14d(33).Intriguingly,asubstantialdecreaseinarginineavailabilityoccursaroundthetime(d8oflife)(33)whensow-rearedpigletsbegintoexhibitsubmaximalgrowth(13).Inaddition,plasmaconcentrationsofammoniaincreasedpro-gressivelyby18–46%,whereasthoseofnitriteplusnitratedecreasedby16–29%,in7-to14-d-oldsucklingpigs,com-paredwith1-to3-d-oldpigs.Thesemetabolicdataonim-pairedhepaticureagenesisandreducedsystemicNOsynthesissuggestahithertounrecognizeddeficiencyofargininein7-to21-d-oldsow-rearedpigs.Althoughpigletscontinuetogrowduringthe21-dsucklingperiod,thisdoesnotnecessarilymeanthatargininesupplyfrommilkplusendogenoussynthesismeetsargininerequirementsfortheirmaximalgrowth(ama-jorgoalofanimalproduction)andoptimalmetabolicfunc-tion,asexemplifiedbysubmaximalgrowthandimpairedNOsynthesisinarginine-deficientyoungrats(35).Argininedeficiencyasagrowth-limitingfactorinyoungpigsAsnotedabove,argininecontentisrelativelylowinsow’smilk(14,15),asreportedforthemilkofhumansandcows(14).Thereisexperimentalevidencesupportingthenotionthatareducedavailabilityofargininemaylimitthemaximalgrowthofyoungpigs.Forexample,Leibholz(36)reportedthatinpigletsweanedat3to4dofagesupplementing0.2and0.4%argininetoadriedmilkdietcontaining19.2%crudeproteinand0.75%arginine(sim