Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase...

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GCKR Pathway of Energy metabolism UDP- glucose glucose G6P F6P F1,6bisP GAP DHAP TPI1 1,3BPG 3PGA 2PGA PEP pyruvate acetyl-CoA citrate isocitrate α-ketoglutarate Succinyl-CoA succinate fumarate malate oxaloacetate TCA cycle pyruvate citrate oxaloacetate malate NADPH acetyl-CoA malonyl-CoA palmitic acid LCFAs unsaturated fatty acid G1P glycogen pentose phosphate pathway glycerol 3-phosphate TG FA acyl-CoA acyl-carnitine acyl-carnitine acyl-CoA acetyl-CoA β oxidation ATP synthesis ATP NADH Electron Transport chain ATP acetoacetyl-CoA acetoacetate 3-hydroxybutylic acid mitochondria peroxisome glucose PYGL,M,B GYS1, 2 UGP2 branched glycogen AGL PGM1,2,3 HK1,2,3,GCK G6PC, G6PC2,3 SLC37A1,2,3,4 (G6P transporter) PFKM,L FBP1,2 ALDOA,B,C GPI GPD1,2 GAPDH PGK1,2 PGAM1,2,4,5 ENO1,2,3,4 PKM, PKLR MPC1,2 PDC PDK1,2,3,4 SLC2A1,2,4,6 (GLUT1,2,4,6) F2,6,bisP PFKFB1,2,3,4 PCK1,2 (PEPCK-C,M) ME1,2,3 IDH1,2,3A,3B SDHA,B,C,D SUCLA2 SUCLG1,2 OGDH CS ACO1,2 FH MDH1,2 PC ACLY ACACA.B (ACC1,2) FASN ELOVL1,2, 3,4,5,6,7 SCD, SCD5 Scd1,2,3,4 MDH1 LPIN1,2,3 glycerol GK AQP9 (transporter) LPA AGPAT1-5 acyl-CoA GPAM(GPAT1) GPAT2,3,4 PA PLPP1-3 DAG DGAT1,2 2-MAG MOGAT1,2,3 LIPE LIPN LIPJ droplet LIPM LIPK(skin) PNPLA1(skin) FITM1,2 FAF1, 2 FABP1-7, 9.12 FFAR3(GPR41) ACSs ACSL1,3-6 ACSM1,2A/B,3-6 ACSS1,2,3 ACSBG1,2 ACSs CPT1A,B,C CPT2 ACADs ACSs SLC25A20(CACT) FADH2 ECHS1, HADHA,B trans Δ2 enoyl-CoA β-hydroxyacyl-CoA HADH, HADHA,B β-ketoacyl-CoA ACAT1,2 PCCA/B ropionyl-CoA MCEE MUT Succinyl-CoA ECI1 DECR1,2 unsaturated acyl-CoA acetone ketone bodies HMGCS1,2 HMGCL BDH1,2 ACAT1,2 complex I complex III complex IV complex II succinate ADP F0 F1 chylomicrons SLC27A1-6 CD36 LPL lactate LDHA,B,C Ala Trp Tyr,Phe Ile,Met,Val propionate Glu His,Pro,Arg Asp GOT1,2 GOT1,2 Gln GLUL GLUD1,2 PHKs glycerol SLC25A1 PLIN1-5 ADP CKs Coenzyme Q10 synthesis COQs CoQ10 phosphorylcreatine shuttle UCP1,2,3 SLC25A27 acyl-CoA EHHADH ECH1 ACOX1,2,3 HSD17B4 HSDL2 ACAA1 (Acaa1a,b) acyl-CoA + acetyl-CoA HACL1 DECR2 ECI2 Saturated FA oxidation Methylated FA Unsaturated FA oxidation FA Acot3 ACOT4 Acot5 ACOT6 ACOT8 acetate ACOT8 ACOT12 acyl- carnitine acetyl- carnitine CRAT CROT ABCD1,2,3 acyl-CoA PEXs Peroxisomal proteins retinol all-trans-retinol all-trans-retinal membrane transport STRA6 DHRS3,4 RDH5 ADH1A,B ADH4 RETSAT all-trans 13,14 dihydro retinol retinoic acid ALDH1A1 FA2H FA SLC27A2 (ACSVL1) ACSL1 PHYH HACL1 ALDH3A2 α-oxidation GBE1 SLC16A1 AACS ACSF2, 3 GPAT4 GYG1, 2 ACOX

Transcript of Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase...

Page 1: Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase coqs adck3 (coq8) coq2 coq3 coq4 coq5 coq6 coq7 coq9 etfdh pdss1(coq1) pdss2(coq10d3)

GCKR

Pathway ofEnergy metabolism

UDP-glucose

glucose

G6P

F6P

F1,6bisP

GAP DHAPTPI1

1,3BPG

3PGA

2PGA

PEP

pyruvate

acetyl-CoA

citrate

isocitrate

α-ketoglutarate

Succinyl-CoA

succinate

fumarate

malate

oxaloacetate

TCA cycle

pyruvate

citrate

oxaloacetate

malate

NADPH

acetyl-CoA

malonyl-CoA

palmitic acid

LCFAs

unsaturated fatty acid

G1P glycogen

pentose phosphatepathway

glycerol 3-phosphate

TG

FA

acyl-CoA

acyl-carnitine

acyl-carnitine

acyl-CoA

acetyl-CoA

β oxidation

ATP synthesis

ATP

NADH

ElectronTransportchain

ATP

acetoacetyl-CoA

acetoacetate

3-hydroxybutylic acid

mitochondria

peroxisome

glucose

PYGL,M,B

GYS1, 2UGP2 branched glycogen

AGL

PGM1,2,3

HK1,2,3,GCK

G6PC, G6PC2,3SLC37A1,2,3,4

(G6P transporter)

PFKM,LFBP1,2

ALDOA,B,C

GPI

GPD1,2GAPDH

PGK1,2

PGAM1,2,4,5

ENO1,2,3,4

PKM, PKLR

MPC1,2

PDCPDK1,2,3,4

SLC2A1,2,4,6(GLUT1,2,4,6)

F2,6,bisPPFKFB1,2,3,4

PCK1,2(PEPCK-C,M)

ME1,2,3

IDH1,2,3A,3B

SDHA,B,C,D

SUCLA2SUCLG1,2

OGDH

CS

ACO1,2

FH

MDH1,2

PC

ACLY

ACACA.B(ACC1,2)

FASN

ELOVL1,2,3,4,5,6,7

SCD, SCD5Scd1,2,3,4

MDH1

LPIN1,2,3

glycerol

GK

AQP9 (transporter) LPA

AGPAT1-5

acyl-CoAGPAM(GPAT1)GPAT2,3,4

PAPLPP1-3

DAG DGAT1,2

2-MAGMOGAT1,2,3

LIPELIPNLIPJ

droplet

LIPMLIPK(skin)PNPLA1(skin)

FITM1,2FAF1, 2

FABP1-7, 9.12

FFAR3(GPR41)ACSs

ACSL1,3-6ACSM1,2A/B,3-6ACSS1,2,3ACSBG1,2

ACSs

CPT1A,B,C

CPT2

ACADs

ACSs

SLC25A20(CACT)

FADH2

ECHS1, HADHA,Btrans Δ2 enoyl-CoA

β-hydroxyacyl-CoA HADH, HADHA,B

β-ketoacyl-CoAACAT1,2

PCCA/Bpropionyl-CoA

MCEEMUT

Succinyl-CoA

ECI1DECR1,2

unsaturated acyl-CoA

acetoneketone bodies

HMGCS1,2HMGCL

BDH1,2

ACAT1,2

complex I

complex III

complex IV

complex II

succinate

ADP

F0 F1

chylomicrons

SLC27A1-6CD36

LPL

lactate LDHA,B,C

AlaTrp

Tyr,Phe

Ile,Met,Valpropionate

GluHis,Pro,Arg

Asp

GOT1,2

GOT1,2

GlnGLUL GLUD1,2

PHKs glycerol

SLC25A1

PLIN1-5

ADP

CKs

Coenzyme Q10 synthesisCOQs

CoQ10

phosphorylcreatine shuttle

UCP1,2,3SLC25A27

acyl-CoA

EHHADH

ECH1

ACOX1,2,3

HSD17B4HSDL2ACAA1(Acaa1a,b)

acyl-CoA + acetyl-CoA

HACL1

DECR2ECI2

Saturated FAoxidation

Methylated FAUnsaturated FAoxidation

FA

Acot3ACOT4Acot5

ACOT6ACOT8

acetate

ACOT8

ACOT12

acyl-carnitine

acetyl-carnitine

CRATCROT

ABCD1,2,3

acyl-CoA

PEXs

Peroxisomalproteins

retinol

all-trans-retinol all-trans-retinal

membrane transport STRA6

DHRS3,4

RDH5ADH1A,BADH4

RETSAT

all-trans 13,14dihydro retinol

retinoic acid

ALDH1A1

FA2H

FA

SLC27A2(ACSVL1)

ACSL1PHYHHACL1

ALDH3A2

α-oxidation

GBE1

SLC16A1

AACS

ACSF2, 3

GPAT4

GYG1, 2

ACOX

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Mitochondrial β-oxidation

ACADVL(ACAD6)

ACAD8-11

ACADM(ACAD1)

ACADL(ACAD4)ACADS(ACAD3)

ACADSB(ACAD7)

Acad12

ACADs

ECHs

HADHA(ECHA)

HADHB(ECHB)

ECHS1

HADHs

HADHHADHA(ECHA)

HADHB(ECHB)

ACATs

ACAT1

ACAT2

enoyl-CoA hydratase

3-hydroxyacyl-CoA dehydrogenase

acyl-CoA dehydrogenase

(3-ketoacyl-CoA thiolase)

acetyl-CoA acetyltransferase

propionyl-CoA carboxylase

methylmalonyl CoA epimerase

methylmalonylCoenzyme A mutase

PCCA

PCCB

MCEE

MUT

propionate metabolism

Δ3,Δ2-enoyl-CoA isomerase

2,4-dienoyl-CoA reductase

ECI1

DECR1,2

unsaturated FA metabolism

acetyl-CoA Acetyltransferase(thiolase)

ACAT1

ACAT2

HMG-CoA synthase

HMG-CoA lyase

HMGCS2

HMGCS1

HMGCL

HMGCLL1

3-hydroxybutyrate dehydrogenase

BDH1

ketone body synthesis

BDH2

electron transport chain

complex I

complex IV

complex III

complex II

NDUFA1-13, 4L, 4L2 NDUFAB1 NDUFAF1-4

NDUFB1-11 NDUFC1,2 NDUFS1-8 NDUFV1-3 MT-ND1-6, 4L

SDHA SDHB SDHC SDHD

UQCRFS1 UQCRC1,2 UQCRH UQCR10,11 UQCRB

UQCRQUQCC1,2,3

BCS1L CYC1UQCRHL MT-CYB

COX1,2,3 COX4I1,2 COX5A,B COX6A1,2 COX6B1,2 COX7A1,2COX6C

COX7B COX7A2LCOX7CCOX7B2 COX8A, Cox8b

COX10,11,14,15,16,17,18,19,20, COA1,3,4,5,6,7 SCO1,2

COX8C

ATP synthesis

F0

F1

MT-ATP6,8 ATP5E/H/I/F1/G1,2,3/J,J2/L,L2/S

ATP5A1/5B/5C1/5D/5E/5O/ ATPAF1,2

PDC:

PDHA1: pyruvate dehydrogenase (lipoamide) alpha 1

PDHB: pyruvate dehydrogenase (lipoamide) beta

DLAT:dihydrolipoamide S-acetyltransferase (Dihydrolipoyllysine-residue acetyltransferase)

PDHX:pyruvate dehydrogenase complex, component X

PDP1: pyruvate dehyrogenase phosphatase catalytic subunit 1

DLD: dihydrolipoamide dehydrogenase

PDHA2: pyruvate dehydrogenase (lipoamide) alpha 2

PDP2: pyruvate dehyrogenase phosphatase catalytic subunit 2

PDPR: pyruvate dehydrogenase phosphatase regulatory subunit

pyruvate dehydrogenase complex

PDK1: pyruvate dehydrogenase kinase, isozyme 1

PDK2: pyruvate dehydrogenase kinase, isozyme 2

PDK4: pyruvate dehydrogenase kinase, isozyme 4

PDK3: pyruvate dehydrogenase kinase, isozyme 3 PDKs

pyruvate dehydrogenase kinase

CKs CKBCKBECKMCKMT1ACKMT1BCKMT2

creatine kinase

COQs

ADCK3 (COQ8)COQ2COQ3COQ4COQ5COQ6COQ7COQ9ETFDHPDSS1(COQ1)PDSS2(COQ10D3)

coenzyme Q

AcylCoA oxidase(ACOX)

ACOX1ACOX2ACOX3

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ELOVLs

ELOVL1

ELOVL2

ELOVL3

ELOVL4

ELOVL5

ELOVL6

ELOVL7PEXs

PEX1

PEX10

PEX11A

PEX11B

PEX12

PEX13

PEX14

PEX16

PEX19

PEX2

PEX26

PEX3

PEX5

PEX5L

PEX6

PEX7

Pentose phosphate pathway

PGD

G6PD

PGLS

RPE

TKT

TKTL1

TKTL2

RPIA

TALDO1

ACSs

ACSS1

ACSS2

ACSS3

ACSL1

ACSL3

ACSL4

ACSL5

ACSL6ACSM1

ACSM2A

ACSM2B

ACSM3

ACSM4ACSM5

ACSM6

ACSBG2

ACSBG1NDUFB1,2,3,4,5,6,7,8,9,10,11

NDUFS1,2,3,4,5,6,7,8

NDUFAF1,2,3,4

NDUFV1,2,3

MT-ND1,2,3,4,5,6

complex I

AGPAT1

AGPAT2

AGPAT3

AGPAT4

AGPAT5

AGPAT

SLC37A2

SLC37A4SLC37A3

SLC37A

SLC37A1

SLC27A1SLC27A2

SLC27A3

SLC27A4

SLC27A5

SLC27A6

SLC27A

FABP1FABP2

FABP3

FABP4

FABP

FABP12

FABP9

FABP7

FABP6

FABP5

PLIN

PLIN5

PLIN4

PLIN3

PLIN2

PLIN1

PHKs PHKA1,2 PHKB PHKG1,2phosphorylasekinase

Page 4: Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase coqs adck3 (coq8) coq2 coq3 coq4 coq5 coq6 coq7 coq9 etfdh pdss1(coq1) pdss2(coq10d3)

PDC

PDKs

αARs

β ARs ADRB1,2,3

ADRA1A,B,DPP1s

GYS1,2 Glycone syntehsis

G6P

AKTs GSK3A,BmTORC1 S6Ks

FGF19(FGF15) FGFR4KLB

MAPK1

cAMPGCGADCY1-10

PDEs:

PHKcomplex PYGs glycogenolysisPKA

INS INSR

GCGRcircadian rhythm

CRY1,2

HK1,2,3

PKM, PKLR

GCKGCG

PKAs

G6P

glycolysis

G6Pase (G6PC, G6PC2, G6PC3)

PC

PCK1,2(PEPCK-C,M)gluconeogenesis

F2,6bisP

PFKFB1,2,3,4

PFKM,L

FBP1,2

SIRT2

FOXO1

CREB1

CEBPA,B

SLC2A1,2,4,6(GLUT1,2,4,6)

Acetyl-CoA synthesis TCA cycle

AMPK

AMPKKs

NR4A1

cytokines

IL6, IL13

STAT3

ITPR3(IP3R) CAMK2A,B,G,D

MAPK14(p38MAPK)

DUSP6(MKP3)

HDAC3

HDAC4,5,7

CREBBP(CBP)

EP300(P300)

Fasting

HNF4A

ERN1(IRE1A)

NR3C1(GR)

CRY1,2

FGF21

PRKCI

INS

PPARGC1A/B(PGC1-A/B)

fasting

SIRT1

CRTC2

SIK2ER stress

EIF2AK3(PERK)

ATF6

ERN1(IRE1)

CREB3L3(CREBH)

XBP1

EIF2S1,2,3

NT5C1A

Wnt signal CTNNB1

Control of Glucose Metabolism

GCKR F6P

ADIPOQ ADIPOR1, 2

LEP LEPR

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PHKs

CALM1(calmoduline)CALM2(calmoduline)CALM3(calmoduline)PHKA1(muscle)PHKA2(liver)PHKBPHKG1(muscle)PHKG2(testis)

AKTsAKT1AKT2AKT3

AMPK

PRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3

AMPKKcomplex

CAB39CAB39LSTK11STRADASTRADB

PDEs:phosphodiesterase

PDE10APDE11APDE1APDE1BPDE1CPDE4APDE4BPDE4CPDE4DPDE7APDE7BPDE8APDE8BPDE9A

PKAs

PRKACAPRKACBPRKACGPRKAR1APRKAR1BPRKAR2APRKAR2B

PDKs

PDK1PDK2PDK3PDK4

G6PasesG6PCG6PC2G6PC3

PYGsPYGBPYGLPYGM

S6Ks

RPS6KA1RPS6KA2RPS6KA3RPS6KA4RPS6KA5RPS6KA6RPS6KB1RPS6KB2RPS6KC1

PP1s

PPP1CAPPP1CBPPP1CCPPP1R10PPP1R11PPP1R12APPP1R12BPPP1R12CPPP1R13BPPP1R13LPPP1R14APPP1R14BPPP1R14CPPP1R14DPPP1R15APPP1R15BPPP1R16APPP1R16BPPP1R17PPP1R18PPP1R1APPP1R1BPPP1R1CPPP1R2PPP1R3APPP1R3BPPP1R3CPPP1R3DPPP1R3EPPP1R3FPPP1R3GPPP1R4PPP1R7PPP1R8PPP1R9APPP1R9B

PDC

DLATDLDPDHA1PDHA2PDHBPDHXPDP1PDP2PDPR

α ARs

ADRA1AADRA1BADRA1DADRA2AADRA2BADRA2C

β ARsADRB1ADRB2ADRB3

MTORC1

AKT1S1(PRAS40)DEPTORRPTOR(RAPTOR)MLST8(mLST8/GβL)MTOR

CAMK2

CAMK2ACAMK2B

CAMK2G

CAMK2D

ADCY1ADCY2ADCY3ADCY4ADCY5ADCY6

ADCY8ADCY7

ADCY10ADCY9

ADCY

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Page 6: Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase coqs adck3 (coq8) coq2 coq3 coq4 coq5 coq6 coq7 coq9 etfdh pdss1(coq1) pdss2(coq10d3)

Control of Lipid Metabolism

AKTs mTORC1

malonyl-CoA

CPT1A,B

lipogenesis

FFA synthesis

TG synthesis

FFA uptake

FFA trafficking

lipolysis

βoxidation

TCA cycle

aerobic energyproduction

ketone body synthesis

Palmitoyl-CoA

PKAs

FOXO1

CREB1

ACACA,BSREBF1,2(SREBP1,2)

DGAT2

Acetyl-CoA synthesis

SLC25A1 citrate

PDC

PDKs

AMPKAcetyl-CoA carboxylase

PPs

AMPKKs

PPARGC1A/B (PGC1-A/B)

PPARA

NR4A1

α ARs

β ARs ADRB1,2,3

ADRA2A,B,CADRA1A,B,D

glycerol 3-phosphate GPAM

Acetyl-CoA

LIPE

cAMPGCG ADCY1-10

PDEs: phosphodiesterase PDE4A,B,C,D (PDE7A,B PDE8A,B PDE9A PDE10A PDE11A PDE1A,B,C)

PKAs

INS INSR

GCGRcircadian rhythm

CRY1,2

24945349

PLIN1-5perilipins

PLCL1,2(PRIP)PP2As

LEP

GH1,2 JAK2 STAT5A,B

SIRT1

DUSP6(MKP3)

ITPR3(IP3R)

CAMK2A,B,G,D

MAPK14(p38MAPK)

Wnt signal CTNNB1

HDAC4,5,7

HDAC3

ER stress

EIF2AK3(PERK)

ATF6

ERN1(IRE1)

CREB3L3(CREBH)

XBP1

EIF2S1,2,3

CRTC2

HES1 PPARG

PPARD

SIK2

MLXIPL(ChREBP)

NR1H3(LXR)NR1H4(FXR)

NROB2

bile acids

cholesterol

CYP7A1

24222088

MLX

SCDs

FASN

glucose

PP2As

CREBBP(CBP)

EP300(P300)

FGF21GCG

CD36NR1I2(PXR)

AHR

APOA4,5,ApoC2

chylomicrons FFALPL

APOC3 CREB3L3(CREBH)

LCFAs

PC

ACADL(LCAD)SIRT3

HMGCS2

All-trans-retinal

RXRA,B,GRARA,B,G

SCAPPC, PIS1P, S2P

Fasting

cholesteral efflux ABCG1ABCA1

oxysterols

FGF19(FGF15)

bile acids

INSIG2

S6K

mTORC1

SREBF1(SREBP1)

HNF4A

HNF4A

Cholesterol synthesis SREBF2HNF4A

LifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes

Page 7: Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase coqs adck3 (coq8) coq2 coq3 coq4 coq5 coq6 coq7 coq9 etfdh pdss1(coq1) pdss2(coq10d3)

PHKcomplexs

CALM1(calmoduline)CALM2(calmoduline)CALM3(calmoduline)PHKA1(muscle)PHKA2(liver)PHKBPHKG1(muscle)PHKG2(testis)

AKTs

AKT1AKT2AKT3

AMPK

PRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3

PP2As

PPP2CAPPP2CBPPP2R1APPP2R1BPPP2R2APPP2R2BPPP2R2CPPP2R2DPPP2R3APPP2R3BPTPA(PPP2R4)PPP2R5APPP2R5BPPP2R5CPPP2R5DPPP2R5E

AMPKKcomplex

CAB39CAB39LSTK11STRADASTRADB

PDEs: phosphodiesterase

PDE10APDE11APDE1APDE1BPDE1CPDE4APDE4BPDE4CPDE4DPDE7APDE7BPDE8APDE8BPDE9A

PKAs

PRKACAPRKACBPRKACGPRKAR1APRKAR1BPRKAR2APRKAR2B

SCDs

SCDScd1Scd2Scd3Scd4SCD5

PDKs

PDK1PDK2PDK3PDK4

perilipins

PLIN1PLIN2PLIN3PLIN4PLIN5

PDC

DLATDLDPDHA1PDHA2PDHBPDHXPDP1PDP2PDPR

α ARs

ADRA1AADRA1BADRA1DADRA2AADRA2BADRA2C

β ARsADRB1ADRB2ADRB3

MTORC1

AKT1S1(PRAS40)DEPTORRPTOR(RAPTOR)MLST8(mLST8/GβL)MTOR

S6Ks

RPS6KA1RPS6KA2RPS6KA3RPS6KA4RPS6KA5RPS6KA6RPS6KB1RPS6KB2RPS6KC1

ADCY1ADCY2ADCY3ADCY4ADCY5ADCY6

ADCY8ADCY7

ADCY10ADCY9

ADCY

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Page 8: Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase coqs adck3 (coq8) coq2 coq3 coq4 coq5 coq6 coq7 coq9 etfdh pdss1(coq1) pdss2(coq10d3)

CREB1(CREB)

FOXO1,3,4,6

MTORC1

S6kPPARGC1A,B(PGC-1A,B)

SREBF1(SREBP-1)

LIPIN1,2

SIK2 CRTC2(TORC2)

CREBBP(CBP)

EP300(P300)

GSK3BPP1

GYS1,2

gluconeogenesis

glycogen synthesis

PFKFB1,2,3,4

F2,6bisP

PFKL,M,P

GCK

HK1,2,3

PDK1,2,3,4 PDC

TSC1

TSC2

RHEB

PDE(PDE3B) cAMP PKA LIPE

glycolysis lipogenesis

lipolysis

MLXIPL(ChREBP)

INSIG2 SCAP SREBF1(SREBP-1)

AMPK

STK11(LKB1)

PRKCI(PKCi/λ) CREBBP(CBP)

ACLY

PP2A

ceramides

PRKDC(DNA-PK)

XRCC6(KU70) XRCC5(KU80)

USF1,2

FASN

GPAM

EIF4EBP1(4E-BP1)EIF4E Protein synthesis

RAS RAF1 MAP2K1,2(MEK1,2) MAPK1,3(ERK2,1) growth

NR1H3,2(LXRa,b)

SGK1,2,3

apoptosis

SCNN1A/B(ENAC1,2) sodium transport

Insulin-pathway and energy metabolism-1

FBP1,2

PYGL,M,B glycogenolysis

ACACsFASN

ACACsFASN

ELK1 FOS

INS

INSR

SHC1,2,3,4

IRS1,2,4

Irs3

GAB1,2,3,4

PI3K

PIP3

PDK1,2,3,4

AKT1,2,3

TNF

TNFR1A,B

IKK

MAPK8(JNK) FYN

FFA

PRKCQ

PRKCE

NO

NOS2

PTENINPP5D(SHIP)

MTORC2

NCK1,2

PTPN1(PTP1B)

PTPN6(SHP1)

PTPN11(SHP2)

AHSG(FETUIN-A)

TLR4

Inflammation

SOCS1-7

ER sress

ROS/mitochondria

GRB2 GRB10

SOS1,2

PRKCZMTORC1

S6K

PKA

GPAMSCDs

ACLYGK

HIF1A

PP1KAT2B(P/CAF)

HDAC9

PRKCI

HMGA1

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AMPK

PRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3

PKA

PRKACAPRKACBPRKACGPRKAR1APRKAR1BPRKAR2APRKAR2B

IKK

CHUKIKBKBIKBKEIKBKG

S6K

RPS6KA1RPS6KA2RPS6KA3RPS6KA4RPS6KA5RPS6KA6RPS6KB1RPS6KB2RPS6KC1

PP2A

PPP2CAPPP2CBPPP2R1APPP2R1BPPP2R2APPP2R2BPPP2R2CPPP2R2DPPP2R3APPP2R3B

PPP2R4PPP2R5APPP2R5BPPP2R5CPPP2R5DPPP2R5E

PI3K

PIK3CAPIK3CBPIK3CDPIK3CGPIK3R1PIK3R2PIK3R3PIK3R4PIK3R5PIK3R6

PDC

DLATDLDPDHA1PDHA2PDHBPDHXPDP1PDP2PDPR

PP1s

PPP1CAPPP1CBPPP1CCPPP1R10PPP1R11PPP1R12APPP1R12BPPP1R12CPPP1R13BPPP1R13LPPP1R14APPP1R14BPPP1R14CPPP1R14DPPP1R15APPP1R15BPPP1R16APPP1R16BPPP1R17PPP1R18PPP1R1APPP1R1BPPP1R1CPPP1R2PPP1R3APPP1R3BPPP1R3CPPP1R3DPPP1R3EPPP1R3FPPP1R3GPPP1R4PPP1R7PPP1R8PPP1R9APPP1R9B

RAS

KRASNRASHRAS

ACACs ACACAACACB

SCDs

SCDScd1Scd2Scd3Scd4SCD5

MTORC2

MTORC1

AKT1S1(PRAS40)DEPTORRPTOR(RAPTOR)MLST8(mLST8/GβL)MTORMAPKAP1(SIN1)PRR5(PROTOR1)PRR5L(PROTOR2)RICTOR

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PDHA1

PDC:

PDHB

DLAT

PDHX

PDP1

DLD

PDHA2

PDP2

PDPR

pyruvate dehydrogenase complex

PYG

PYGL

PYGM

PYGB

PDEs:phosphodiesterase

PDE10APDE11APDE1APDE1BPDE1CPDE3APDE3BPDE4APDE4BPDE4CPDE4DPDE7APDE7BPDE8APDE8BPDE9A

SOCS1SOCS2

SOCS3

SOCS4

SOCS5

SOCS6

SOCS7

SOCS

LifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes

Page 11: Pathway of Energy metabolism - lifeseq.com · cks ckb ckbe ckm ckmt1a ckmt1b ckmt2 creatine kinase coqs adck3 (coq8) coq2 coq3 coq4 coq5 coq6 coq7 coq9 etfdh pdss1(coq1) pdss2(coq10d3)

SLC2A4(GLUT4)

translocation

EHD1 EHBP1

SNARE complex

CAV3 FLOT1

SH2B2(APS)

CBL

STXBP3(Munc18c)

PP2ATBC1D4(AS160)

14-3-3TBC1D1

14-3-3

CRK(CRKII)

RAPGEF1(C3G)

RHOQ(TC10)

TRIP10(CIP4)

RAC1

CAP1,2

AMPK

INS

INSR

SHC1,2,3,4

IRS1,2,4

IRS3

GAB1,2,3,4

PI3K

PIP3

PDK1,2,3,4

AKT1,2,3

TNF

TNFR1A,B

MAPK8(JNK)FYN

FFA

PRKCQPRKCE

NO

NOS2

PTENINPP5D(SHIP)

MTORC2

NCK1,2

PTPN1(PTP1B)

PTPN6(SHP1)

PTPN11(SHP2)AHSG(FETUIN-A)

TLR4

Inflammation

SOCS1-7

ER stress

ROS/mitochondria

GRB2 GRB10

SOS1,2

PRKCZ

PRKCI

HMGA1

Insulin-pathway and energy metabolism-2LifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes

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AMPK

PRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3

IKK

CHUKIKBKBIKBKEIKBKG

PI3K

PIK3CAPIK3CBPIK3CDPIK3CGPIK3R1PIK3R2PIK3R3PIK3R4PIK3R5PIK3R6

PKA

PRKACAPRKACBPRKACGPRKAR1APRKAR1BPRKAR2APRKAR2B

PP1

PPP1CAPPP1CBPPP1CCPPP1R10PPP1R11PPP1R12APPP1R12BPPP1R12CPPP1R13BPPP1R13LPPP1R14APPP1R14BPPP1R14CPPP1R14DPPP1R15APPP1R15BPPP1R16APPP1R16B

PPP1R17PPP1R18PPP1R1APPP1R1BPPP1R1CPPP1R2PPP1R3APPP1R3BPPP1R3CPPP1R3DPPP1R3EPPP1R3FPPP1R3GPPP1R4PPP1R7PPP1R8PPP1R9APPP1R9B

PP2A

PPP2CAPPP2CBPPP2R1APPP2R1BPPP2R2APPP2R2BPPP2R2CPPP2R2DPPP2R3APPP2R3B

PPP2R4PPP2R5APPP2R5BPPP2R5CPPP2R5DPPP2R5E

S6K

RPS6KA1RPS6KA2RPS6KA3RPS6KA4RPS6KA5RPS6KA6RPS6KB1RPS6KB2RPS6KC1

RASKRASNRASHRAS

PDC

DLATDLDPDHA1PDHA2PDHBPDHXPDP1PDP2PDPR

MTORC2

MTORC1

AKT1S1(PRAS40)DEPTORRPTOR(RAPTOR)MLST8(mLST8/GβL)MTORMAPKAP1(SIN1)PRR5(PROTOR1)PRR5L(PROTOR2)RICTOR

SNARE complex

SNAP23

STX4

VAMP2

SOCS1SOCS2SOCS3SOCS4

SOCS5

SOCS6

SOCS7

SOCS

LifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes