Inflammation Pathways & the NADPH Steal€¦ · Inflammation Pathways & the "NADPH Steal"...
Transcript of Inflammation Pathways & the NADPH Steal€¦ · Inflammation Pathways & the "NADPH Steal"...
Fe2+PLP
SLC25A38/ABCB10
ABCB6
Prophobilinogen
Hydroxymethylbilane Protoporphyrinogen IX
Coporphyrinogen IIICoporphyrinogen III
Krebs Cycle
Proteins
Fatty Acids,Glycerol
Cholesterol
Carbohydrates
Amino Acids
Pyruvate Lactate
B1, B2, B3, B5, Lipoate
Acetyl CoA
OxaloacetateCitrate
Cis-Aconitate
D-Isocitrate
Malate
Fumarate
Succinate
Succinyl-CoA
Alpha-ketoglutarate
NADH
Complex I
Complex II
Complex III
Complex IV
O2
Mg
ACAT
Carnitine
Keto Acids
B1, B2, B3, B5, Lipoate
ACAT
ATP
Biliverdin Bilirubin
CO
HMOX
ROSStimulates
HMOX
Keap1 Nrf2
ATM
Ferritin
Glycine
ALAS
ALAD
HMBS
UROS URODCPOX
PPOX
Glyphosate
Molybdenum,B2
Low Heme resultsin Low Sulfate
Aldosterone
NOX
Luteolin Olive LeafApigenin
Stress
Glucose 6-Phosphate
G6PD
Glucose
HK
ADP
ATP
NADP+
NADPH
6-phosphogluconate
Pentose PhosphatePathway
NADP+
Excrete Potassiumand Hydrogen Ions
and hold Sodium
2 GSH
GSSGNADPH
NADP+
HEME
CO
NADPH &CYP450
Reductase
HEME
Biliverdin
NADPH &CYP450
Reductase
HEME
Ferritin
NADPH &CYP450
Reductase
Uroporphyrinogen III
Cysteine
CDOCysteineSulfinate
Fech
Homocysteine
CBS
Cystathionine
CTH HS-S2O3
2-
Thiosulfate
SO32-
Sulfite
SO32-
SO42-
Sulfate
SUOX
SUOX
CBS &CTH
Taurine
Taurine Spares Sulfur
Hypotaurine
SUOX isHeme Dependent
Homocysteine &Sulfites stimulate
NOX
Diet &Supplements
Preservativesand inhalingsulfur dioxide
PAPS3'-phosphoadenosine
5'-phosphosulfate
SULTPAPS
PAP
Excretedin Urine
Dopamine
Smoking
Iron
Angiotension II
Glutamate
Tryptophan N′-Formylkynurenine Intermediates
TDO,IDO1, IDO2
QuinolinicAcid
NADNAD+
NADP+
NADH
NADPH
NAMN
QPRT NMNATNAD
Kinase
ATP
ADP
ADP
ATP
HemeDe Novo Pathway
Dietary formsof Niacin
Preiss-Handler Pathway
Niacin &Nicotinamide Riboside
NAPRT
Pau D' Arco
NADS
CD38
Apigenin,Luteolin
NADPH
Krebs CycleKrebs Cycle
ME1
GTP
ALA
ALA
NADP+
NADPH
O2
NADP+
NO
Citrulline
NOS
Arginine
BH4Oxidative Stress
BH2
GPXSeSG
GPXSeSOH
GSH
GPXSeOH
H2O
H2O
TrxRed
TrxOXNADPH
NADP+
PrxSH PrxSOH PrxSOOH
PrxS-SPrx
H2O2
GlutathioneGSH reductase
Trx reductase thioredoxinSlow step
sulfiredoxin
H2O + O2
O2-
Cl-
HOCL
OH- + Cl-
Fe3+
Fe2+
Hypochlorous acid
NO
PeroxynitriteONOO-
ONOOH Peroxynitrousacid
iNOS
OH-
Heme Oxygenase(HO-1)
Polyunsaturated fatty acidsRO- + RO2
- Lipidhydroperoxides
β-carotenoidradical
β-carotene
OH O-
Ascorbate Dehydroascorbicacid
∝-tocopherol ∝-tocopherol
PARP
Malate
Pyruvate
Isocitrate
NADP+
NADPH
Alphaketogluterate
Heme
NADP+
NADPH
Glyoxylate
AGXT
Glycolate
Alanine
Pyruvate
GRHPR
NADPH NADP+
Oxalate
LDH
NADH
NAD+
GlyoxalateMetabolism
Histamine
Oxalates
HistamineRaising Foods
ABP1DAO
AllergensDiesel Exhaust
Histidine
HNMT
HDC
B6
SAMe
MAO
N-Methylimidazoleacetic acid
ImidazomeAcetaldehyde
ALDH
Imidazole acetic acid
Fats
Angiotension I
ACE
LF-EMF
Sulfites
mTOR
CurcuminSpirulina
CATCatalase
SODSuperoxideDismutase
Vasodilation andElectron Donor
Heme
Fe2+
HMOX-1
NOX
GSH NitrosoglutathioneNitric Oxide(reservoir)
BH4
BH2O2
-
Damage toProtein
Carbohydrateand DNA
Fe2
NADPH
CYP450 Reductase
Ammonia
Citruline
Arginine
ArginosuccinicAcid
AspartateOrnithine
Urea
SIRT1
Sirt3
AMPK
FOX03A
SOD2
IDH2
OTC(urea cycle)
CAT(Catalase)
P53
FOX01
NADPHSynthesis
SOD andAntioxidants
Glucose & OtherSugars
MastCells
Histamine
Cytokines
TNF-a
IL-13
LeukotrinesProsta
glandins
IgE
Luteolin &HMOX
KIT
To GlutathioneProduction
Homocysteine
CBS
Cysteine Glutamine
CTH
Sirt3
SIRT3 ControlsAMPK
y-Glu-Cys
GCLM& GCLC
Glycine
ATP
ADP
ATP
ADP
GSS
GSH(Reduced
Glutathione)
GSSG(Oxidized Glutathione)
GSR
GLRXNADPH
Xenobiotics
GST's
GSH-S-conjugate
Stool Urine
CYP 450
Phase 1Detox
Bile
MethionineMAT
AHCY
SAMe
SAH
BHMT
TMG
DMG
PEMT
MTRRMTR
B12
MTHFR
NRF2
Keap1Glutamate
GLS
GLUL
GABA
GAD
B6 and Magnesium
Excitatory - Simulates NOX Relaxing
InfectionInflammation
Chronic Stress andGlucocorticoid Elevations
Glutamine Synthase
Glutamate Synthase
Xenobiotics
BRCA1
FH
CDKN1A
Inflammation Pathways & the "NADPH Steal"
Glutathione Production
NADPH Production
Transsulfuration
Urea Cycle
FentonReaction
Fech HMOX
Genetics Variants Impacting Iron Dysregulation
FTL TFR2
HFE CP AC01 TF
SLC11A2DMT1
SLC40A1Ferroportin
Glycine +Succinyl-CoA
Zn2+
Lipoic Acid
Porphyrins will blockGABA receptors
FECH dependent oniron-sulfur clusters
Fe2+
FAD
PPIX
Zn2+,P5P
Fe3+
Lead
Elevated HEME(if HMOX lessthan optimal)
Poor conversionwill limit Heme
Nrf2
Glutathionereleased from
HEME
mTOR Stimulation
GrowthHormones
Glutamine
IronPlastics
Xenoestrogens
FolateDairy/Amino
AcidsInsulin/Carbs
Porphyrins andProtoporphyrins
GABAReceptors
Anxiety if blocked
Copyright 2018
Contributors to this map creation were:
Robert Miller, CTNMatthew MillerLari Young, MDEmily Givler, DSCBeth O'Hara, MAMackay Rippey, LAc
Reproductions of this map withoutpermission of NGRI is forbidden.
This pathway map is for informational, educational and research purposes only.
This map was not intended to provide diagnosis or treatment for any disease,and all users of this map agree to hold NGRI and the creators of this pathwaymap harmless for how they may use it.
Although great care was taken to ensure accuracy, errors may have occurredor further research or findings may contradict the pathways and interactions.
Nrf2
HemeCu, Zn
HemeMn
Nrf2
Nrf2Heme
Very high doseNicotinamide
Leptin ResistanceIGF-1
Vitamin DReceptor
Sirt1 potentiatesVit. D Receptor
DNA Repair
alpha-ketogluterate
GDH
GDH
Glutamate toAlpha-ketogluterate
OrnithineTranscarbamylase
ResveratrolBerberine
SIRT3 activates AMPK
Autophagy
Phase IIGlutathione Conjugation
Phase IISulfation
Borrelliaburgdorferi
DARC
DNA Repair
Oxalates stimulateNADPH Oxidase (NOX)
Succinyl-CoA To Heme Cycleto produce Heme
May simulateMast Cells
Catecholamines,Hormones,
Xenobiotics &Toxins
Pantethine
PANK
Deactivation and bioactivation of xenobioticsInactivation of hormones and catecholaminesStructure and function of macromoleculesElimination of end products of catabolism
OTC
ARG1
ASS1
ASL
SIRT3 StimulatesOTC
Folate Cycle
Shared in NOS Cycle
NOS
Tryptophan Tyrosine
Serotonin Dopamine
NitricOxide
Ammonia will deplete BH4 ifUrea Cycle weak or overwhelmedBH4
NOX Homocysteine canstimulate NOX to make free radicals
MastCells
Phase IIDetox
Norepinephrine
Epinephrine
MAO
COMT
Homovallinate
COMT
COMT
VMA
VMA
SAMe & Mg
SAMe & Mg
SAMe & Mg
LipidPeroxidation
VasodilationAnti-inflammatory
NOX Excess Dopamine will stimulateNOX and mast cells
Phase IIMethylation
NAT
Toxin, Xenobiotic
Ac-CoA CoA
Excretion
Phase IIAcetylation
NAT
Ac-CoA
CoA
Acetyl-Histamine
B6
Methylation andPhase II Methylation
StimulatesInhibits
Enzyme
Contributes to inflammationor mast cells degranulation
Food or Supplement
Co-factor
Free Radical
Free Radical or Damaging
Legend
NOX
HemoglobinMyoglobinNeuroglobinCytochrome p450Chtochrome c -Electron TransportPeroxidaseCatalaseNADPHTryptophan PyrrolaseNitric Oxide SynthaseSUOX
HEME plays a role in each of these
HEME
Heme
Byproduct ofKrebs Cycle
Bilirubin
Glutathione
ThioredoxinDHFR QDPR
N-MethylHistamine
Autophagy
GTPCH
Dietary &Supplemental
Glutamine
Homocysteine
MOLD
IL-4
Cortisol
Coenzyme A Acetyl CoA
ACAT2
AdrenalGlands
Hypothalamus PituitaryCRH ACTH
MastCellsStress
SIRT3
NAD+
NADH
Cystathionine
Function
Organ orGland
IDH
IDH
α-KGDH
Aconitase
Aconitase
SCS
SDH
Fumarase
MDH
CitrateSynthase
CoA
FOLR1 FOLR2 SLC19A1
Food basedFolate
MTHFD1
FolicAcid
DHF
B2, B3
THF
10 Formyl THF
5-10 Methylene-THF
5-10 Methy THF
DHFR
DHFR
MTHFD1
MTHFD15 Methyl THF
HydroxylRadicals
Peroxynitrite
BH2SAMe QDPR
UreaCycle
GSH+ GSNO
ULK1
ULK2
ATG13
mTOR
Nrf2
CO
Carbon Monoxidestimulates PPP
Resveratrol &Turmeric
Berberine andLithium
NO GSH+ GSNO
Transports NO
GSSG GSH
GSNOR
NMDAAMPA
Binds with Glutamate
H2O2
O2-
Nitric Oxide
O2-
O2
Nitric Oxide
Melatonin
5-HIAA MAOA
NQO1
SIRT3 activates IDH2 tosupport NADPH production
IDH3
Resveratrol
EMF
DHFR
Phase IIAcetylation
The "NADPH Steal"
Represents one of the following:compound or molecule orvitamin or intermediate
HO
HO
HO
GSR GLRX
B3
B2
B1, B2, B3, B5, Lipoate
B3, Mg, Mn
Cysteine, Fe++
PARP is responsible for DNA repair