Glycolysis and GBE1 Glycogen Gluconeogenesis in Liver ... · Glycogen UDP-Glucose Gluconeogenesis Glycolysis Pyruvate Lactic acid Alanine Ribose-6-P Pentose phosphate pathway Uric

glucoseG6P

G1P

Glycogen

UDP-Glucose

GlycolysisGluconeogenesis

Pyruvate

Lactic acid

Alanine

Ribose-6-P

Pentose phosphatepathway

Uric acid

GBE1

GYS1, 2

G6PC2, 3

GK

PGM1

PYGMUGP2

PHKA2 PKABeta adrenergic Receptors

GCKR

Acetyl CoAACLY

GSK3B

AKT1, 2 INSRIRSPI3K

TCA cycle citrateFatty acid oxidation

respiratory chain

UCP1, 2, 3

Heat

ATP synthases

ATP

H+H+ H+

mitochondria

Glycolysis and Gluconeogenesis in Liver

PKLR

G6PDPGD

OAA

malateME1

SLC2A2(GLUT2)glucose

F6P

F1,6,P

FBP1, 2 PFKL

SREBF112061893 PRKCD

AMPK

LEPR

ADIPOR1, 2

CAMKK1, 2

Ca++

PKA cAMP

PPARGC1A CRTC2

FBXW7

TSC1TSC2

RHEB

MTORC1

PDK1

RPS6KB1EIF4EBP1

LPIN1, 2

NR1H3(LXR)

FOXO1

MLXIPL(CHREBP) MLXIPL(CHREBP)

PPTPA(PPP2R4）PPP2R1A

PPP2CA, B

PKA

PP2A

EP300CREBBPOGT

MLX

phosphoenolpyruvic acid, PEP

PEP

PCK1

NR1H4(FXR)

Bile acid

oxysterols

AGL

ENO1,2,3,4

G6PCLifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes

AMPK

PRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3

PI3K

PIK3CAPIK3CBPIK3CDPIK3CGPIK3R1PIK3R2PIK3R3PIK3R4PIK3R5PIK3R6

PKA

PRKACAPRKACBPRKACGPRKAR1APRKAR1BPRKAR2APRKAR2B

β ARsADRB1ADRB2ADRB3

PP2A PP2Aalpha subunit PPP2CAPP2Abeta subunitPPP2CBPP2Agamma subunit

(Protein phosphatase 2A)

PPP2R1APPP2R1BPPP2R2APPP2R2BPPP2R2CPPP2R2DPPP2R3APPP2R3BPPP2R4PPP2R5APPP2R5BPPP2R5CPPP2R5DPPP2R5ESTRN(PPP2R6A)

STRN3(PPP2R6B)STRN4(PPP2R6C)

Strm(Strn2)

PP2Agamma subunit

IRS

IRS1

IRS2

Irs3

IRS4

MTORC1

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

LifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes

Pyruvate Lactic acidAlanine

SREBF1 PRKCD

Acetyl CoA

FA

Malonyl CoA

Fatty acyl-CoA

Triglycerides(TG)

ACACAACLY

FASN

GPAM

DGATs

PNPLA2(ATGL)LIPE(HSL)

LIPE(HSL)

FA DG

MGFA

MGLLFA

glycerol

AKT1, 2 INSRIRSPI3K

SCD

TCA cycle

citrate

Fatty acid β-oxidation

respiratory chain

UCP1, 2, 3

Heat

ATP synthases

ATP

H+H+ H+

mitochondria

PKLR

OAAmalate

ME1

12061893

F6P

F1,6,P

AMPK

LEPR

ADIPOR1, 2

CAMKK1, 2

Ca++PKA cAMP

PCK2(PEPCK)

PPARGC1ACRTC2

mTORC1

VLDLLPL

IDL LDLtransport

3-Hydroxybutyric acid

BDH1, 2 acetone

HMGCS2

AcAcCoA

HMGCoA

HMGCL

acetoacetate

ACAT1

VLDLR

HMGCR

Lipid metabolism in Liver

MLXIPL(CHREBP) MLXIPL(CHREBP)

PPTPAPPP2R1A

PPP2CA, B

PKA

PP2A

EP300CREBBPOGT

MLX

ACOT1

PDK1

NR0B2(SHP)NR1H4(FXR)

Bile acid

NR1H3(LXR)

oxysterols

Enoyl-CoA

LTB4

HETEs

16:0/18:1-GCP

CPT1A

peroxisome

Fatty acid β-oxidation

ACOX1, 2, 3

THRA, B

PPARD

Artherogenicdyslipidaemia

VLDL-TG↓

LDL↓

HDL-choresterol↑

FA-oxidation↑APOA1, 2

PPARARXRA

MED1

29558390

oxidative stress

FGF21 NFE2L2EIF2AK1

ANGPTL4

ALDH3A2CPT2

19805517

20378851

LPIN2ST3GAL5

29289645ATF4


AMPK

PRKAA1PRKAA2PRKAB1PRKAB2PRKAG1PRKAG2PRKAG3

PI3K

PIK3CAPIK3CBPIK3CDPIK3CGPIK3R1PIK3R2PIK3R3PIK3R4PIK3R5PIK3R6

PKA

PRKACAPRKACBPRKACGPRKAR1APRKAR1BPRKAR2APRKAR2B

PP2A PP2Aalpha subunit PPP2CAPP2Abeta subunitPPP2CBPP2Agamma subunit

(Protein phosphatase 2A)

PPP2R1APPP2R1BPPP2R2APPP2R2BPPP2R2CPPP2R2DPPP2R3APPP2R3BPPP2R4PPP2R5APPP2R5BPPP2R5CPPP2R5DPPP2R5ESTRN(PPP2R6A)

STRN3(PPP2R6B)STRN4(PPP2R6C)

Strm(Strn2)

PP2Agamma subunit

IRS

IRS1

IRS2

Irs3

IRS4

MTORC1

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


Cholesterol / Bile Acid Synthesis and Secretion in Liver

SLC4A2

Bile Duct

Canalicular

ABCG5

ABCG8Cholesterol

ABCB4(MDR2, 3)Phospholipids

ABCB11(BSEP)

ABCC2(MRP2)Bile acid

Bile

SLC10A1(NTCP)

SLCO1B1(OATP2)

Na+

MDM4(MRP1)

ABCC3(MRP3)

ABCC4(MRP4)

SLC51A(OSTA)

SLC51B(OSTB)

Glycocholic acid

Taurocholic acid

Bile acid Bile acid Bile acid

NR0B2(SHP)

NR1I2(PXR)

PPARA

Cholesterol

Cholyl-CoA

CYP7A1

CYP8B1

NR1H4(FXR)

NR1I3

NR3C1(GR)

SLC4A2(AE2)

Acetyl CoA

AcAcCoA

HMGCoA

mevalonic acidHMGCR

ACAT1

HMGCS2

MVK

7α-Hydroxycholesterol

Bile acid

NR1H3(LXR) oxysterols

HNF4A

NR5A2(LRH1)


SLC10A1(NTCP)

ABCG5

ABCB11(BSEP)

NR0B2(SHP)

NR1I2(PXR)

NR1I3

PPARA

Cholesterol

7α-Hydroxycholesterol

Cholyl-CoA

CYP7A1

CYP8B1

Na+

Cholesterol

Phospholipids

NR3C1(GR)

Canalicular

Cl-

HCO3-

Bile acid

Bile acid

Bile DuctBile

Bile acid

Regulation of Bile acid synthesis and transportIn Liver

NR1H4(FXR)

MDM4(MRP1)

ABCC3(MRP3)

ABCC4(MRP4)

ABCG8

ABCB4(MDR2, 3)

ABCC2(MRP2)

SLC4A2(AE2)

Taurocholic acid

Glycocholic acid

SLC51A(OSTA)

SLC51B(OSTB)

SLCO1B1(OATP2)


αLA(Alpha linolenic acid)

ETA(eicosatetraenoic acid)

EPA(eicosapentaenoic acid)

DHA(docosahexaenoic acid)

PGH2

PGI2 PGE2 TX2 LTB2PGD2

5HPETE

2AG(2-Arachidonoylglycerol )

AEA(arachidonoylethanolamide)

PE(phosphatidylethanolamine)

OEA(Oleoyl ethanolamide)

GPR119

20 HETE (20-hydroxyeicosatetraenoic acid)

8-HETE(8-hydroxyeicosatetraenoic acid)

5-HETE(5-hydroxyeicosatetraenoic acid)

13-OXO-ODA

13-HODE

15-HETE9-OXO-ODA

15d-PGJ3(15-deoxy-δ(12,14)-prostaglandin J3)

15d-PGJ2 (15-deoxy-δ(12,14)-prostaglandin J2)

LA(Linoleic acid)

GLA(gannma-linolenic acid)

DGLA(dihomo-gamma-linolenic acid)

AA(arachidonic acid)

PPARs

DHEA(decosahexaenoylethanolamide)

EPEA(eicosapentanoylethanolamide)

PGE3 TX3 LTB3

(5- Hydroperoxyeicosatetraenoic acid)

(13-(S)- hydroxyoctadecadienoic acid) (13-oxo-9,11-octadecadienoic acid)

CNR1, 2

Resolvin

protectin

lipoxin

FAAHn-acyltransferases

NAPEPLD

NAPEDAGLA, B

PLCs

PLDs

ELOVL5

FADS2FADS1

EVOVL5FADS2

ELOV2, 5 FADS2 ACOX1

Circadian rhythm

Anti-inflammation

obesity

Formation of bioactive lipids

PLA1A


PPARs

PPARA

PPARGPPARD

n-acyl transferases

AANAT:aralkylamine N-acetyltransferase

NAA10(ARD1A）:N(alpha)-acetyltransferase 10, NatA catalytic subunit

GNPNAT1：glucosamine-phosphate N-acetyltransferase 1

HGSNAT：heparan-alpha-glucosaminide N-acetyltransferase

NAA35(MAK10)：N(alpha)-acetyltransferase 35, NatC auxiliary subunit

NAT1: N-acetyltransferase 1


NAA20(NAT3, NAT5):N(alpha)-acetyltransferase 20, NatB catalytic subunit


NAT8:N-acetyltransferase 8 (putative)

NAT8L: N-acetyltransferase 8 like

NAT9: N-acetyltransferase 9 (putative)


NAA40(NAT11): N(alpha)-acetyltransferase 40, NatD catalytic subunit

NAA30(NAT12): N(alpha)-acetyltransferase 30, NatC catalytic subunit

NAA50(NAT13): N(alpha)-acetyltransferase 50, NatE catalytic subunit

NAT14:N-acetyltransferase 14 (putative)

NAA60(NAT15): N(alpha)-acetyltransferase 60, NatF catalytic subunit

NAT16: N-acetyltransferase 16 (putative)


PLD1, 2, 3, 4, 5, 6PLDs

PLCs

PLCB1

PLCB2

PLCB3

PLCB4

PLCG1

PLCG2

PLCD1

Plcd2

PLCD3

PLCD4

PLCE1

PLCL2 (PLCE2)

PLCZ1

PLCH1

PLCH2

PLCL1


Amino Acidα-ketonic acid

Glu2-oxoglutarate

(Arg, His, Pro)

Gln

Amino acid metabolism in liver

citrate

isocitrate

oxaloacetate

malate

fumarate

succinate

Succinyl-CoA

2-oxoglutarate

cis-aconitate

ACLY

ACO2

ACO1, 2

IDH3A, B, G

OGDHCSUCLG1

SDHA, B, C, D

FH

MCCC1, 2

Acetyl CoA

Pyruvate

PDC

TCA cycle

acetoacetate

GPT

PEP

Fatty acid

gluconeogenesis

Ala

GlyCys

Ser

Try

Glu

ArgHis

Pro

Gln

Leu

ME1, 2PCK1, 2

GlycolysisSHMT1, 2

SDSGCAT

GLUD1, 2

Orn

ARG1

OAT

PRODHPRODH2

UROC1

HAL

AMDHD1

GLS

GLS2

Val

Ile

BCAT1, 2IVD HMGCL

Thr

Lys

AADAT

GCDH

Trp

Phe

PAH TATHPD

HGDGSTZ1

FAH

MAT1A MetMAT2A

CBSCTH

CDO1

GOT1

MDH2

AASSALDH7A1

OGDHDLST

ECHS1EHHADH

ACAT1, 2

BCAT1, 2

BCKDHA, BDBT

DLD

ACADSB

IVDACADM

ACADS

HMGCLHMGCLL1HIBADH

ACAA2HMGCS1

OXCT1OXCT2

AACSACAT1

ACAT2ABAT

ALDH6A1

AGXT2

ALDH2

ALDH1B1ALDH9A1ALDH3A2ALDH7A1AOX1

PCCAPCCB

ACSF3

MCEEMUT

IL4I1

ACAD8

ECHS1

MCCC1MCCC2AUHHIBCH

EHHADH

HSD17B10

HADHA, B ACAA1

HMGCS2

MAT2B

DNMT1

DNMT3ADNMT3B

AHCYL1AHCYL2

AHCYCBSL

GOT2MDH1MDH2

CTH

MPSTTST

PYCR1

PYCR2PYCRLALDH4A1

ARG2

FTCD

Asp

AsnASNS

GOT1, 2

NIT2

IL4I1DDO

GLSGLS2 GLUL

NIT2Leu

GOT1, 2IL4I1 AOX1

FAHD1

OGDHL

HADHA

HMGCLL1AUH

ACADM

DBTBCKDHA, B

SDSL

GPT2AGXT AGXT2

GAD1GAD2ABATALDH5A1 GABA

ACMSDHAAO

KYNUKMO

AFMID

TDO2IDO1, 2

HADH

ALDH4A1

ADSSL1ADSSASS1

ADSLASL

Acetoacetyl-CoA

OXCT1, 2HMGCS1, 2

HMGCLHMGCLL1

ACAT1, 2

Acetyl CoA

β-hydroxybutyrateBDH1, 2

α-oxobutyrate(α-ketobutylate)

Propionyl-CoA

Methylmalonyl-CoAMUT

PCCA, BALDH6A1MCEE

BCKDHA, BDBT

ACSS1, 2, 3


PDC

DLATDLDPDHA1PDHA2PDHBPDHXPDP1PDP2PDPR

OGDHC OGDH

DLST

DLDoxoglutarate dehydrogenase complexLifeSeq Co. Ltd.

Molecular Map of Obesity and Diabetes

Mitochondrial Shuttles in liver

citrate

isocitrate

oxaloacetate

malate

fumarate

succinate

Succinyl-CoA

2-oxoglutarate

cis-aconitate

ACLY

ACO2

ACO1, 2

IDH3A, B, G

OGDHC OGDHDLST

DLDSUCLG1

SDHA, B, C, D

FH

Acetyl CoA

Pyruvate

PDC

TCA cycle

PEP

DLD

PDHA1 PDHBDLAT

Fatty acid

Glu

ME1-2

PCK1, 2

GLUD1, 2

Pyruvate

MDH2

SLC25A11

SLC1A3

malate

oxaloacetate

MDH2

aspartate

glutamate

alpha-ketoglutarate

GOT2 GOT2

Malate-aspartate shuttle

oxaloacetate

malate

MDH1

Acetyl CoA

aspartate

GOT1

SLC25A1

Malate-citrate shuttle

Dihydroxyacetonephosphate

glycerol-3-phosphate

GPD1

NADH NAD+

GPD2 FADFADH+

Q QH2

glycerol phosphate shuttle

NADH

NAD+

NADH

NAD+


PDC

DLATDLDPDHA1PDHA2PDHBPDHXPDP1PDP2PDPR

OGDHC OGDH

DLST

DLDoxoglutarate dehydrogenase complexLifeSeq Co. Ltd. Molecular Map of Obesity and Diabetes

Documents

Glycolysis and GBE1 Glycogen Gluconeogenesis in Liver ... · Glycogen UDP-Glucose Gluconeogenesis Glycolysis Pyruvate Lactic acid Alanine Ribose-6-P Pentose phosphate pathway Uric