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Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 NAD -2 CoASH 6C 2 x 3C 2 x 3C 2x 2C Glycolysis

Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

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Malate Fumarate Succinate Succinyl- CoA OAA 2-KG Citrate Acetyl-CoA CO 2 Isocitrate 4C 2C 6C 4C CoASH + NAD NADH + H + NAD NADH + H + CoASH ADP ATP CoASH FAD FADH 2 NAD NADH + H + FAD + 2 ATP NAD + 3 ATP 3 ATP + NAD CO 2 + O 2 TCA / Respiration

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Page 1: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

GlucoseATPADP

ATPADP

PDHC

Acetyl-CoA

CoASH + NAD

CO2 + NADH + H+

T3P

PEP

Pyruvate

ADPATP

ADPATP

NADNADH + H+GAPDH

-2 ATP

+4 ATP

-2 NAD

-2 NAD

-2 CoASH

6C

2 x 3C

2 x 3C

2x 2C

Glycolysis

Page 2: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Glycolysissimplified

Glucose

2 Acetyl-CoA

2 CoASH + 2 NAD

2 CO2 + 2 NADH + 2 H+

2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

Page 3: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Malate

Fumarate

Succinate

Succinyl-CoA

OAA

2-KG

Citrate

Acetyl-CoA

CO2

Isocitrate

4C

2C

6C

4C

CoASH + NAD

NADH + H+

NAD

NADH + H+

CoASH

ADPATP

CoASH

FADFADH2

NAD

NADH + H+

FAD + 2 ATP

NAD + 3 ATP

3 ATP + NAD

3 ATP + NAD

CO2

+ O2TCA / Respiration

Page 4: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

2 Acetyl-CoA

6 NADH + 6 H+2 FADH2 + 2 H+2 ATP

2 CoASH

TCA / Respirationsimplified

18 ATP + 6 NAD4 ATP + 2 FAD

Page 5: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

2 Acetyl-CoA

2 Acetate

2 ADP

2 ATP

2 CoASH

2 Acetyl~P

Pi

Acetate Fermentation

2 Acetyl-CoA

2 Acetate

2 ADP2 ATP

2 CoASH

simplified

An alternative

Page 6: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Glucose

2 Acetyl-CoA

2 CoASH + 2 NAD

2 CO2 + 2 NADH + 2 H+

2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

Respiration

6 NADH + 6 H+2 FADH2 + 2 H+2 ATP

18 ATP + 6 NAD4 ATP + 2 FAD

6 ATP + 2 NAD

6 ATP + 2 NAD

2 CoASH

38 ATP

Glucose

2 Acetyl-CoA

2 CoASH + 2 NAD

2 CO2 + 2 NADH + 2 H+

2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

Fermentationversus

2 Acetate

2 ADP2 ATP

< 4 ATP

2 CoASH

Page 7: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Glucose

2 Acetyl-CoA

2 CoASH + 2 NAD

2 CO2 + 2 NADH + 2 H+

2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

To recycle NADsacrifice energy (ATP)

4 ATP

2 Lactate

2 NAD2 NADH+ 2 H+

2 ATP

2 ATP2 NAD + 2 CoASH

2 NADH + 2 H+

2 NAD

2 Ethanol

2 NADH + 2H+

2 CoASH

2 Pi

2 Acetate

2 ADP

2 ATP

Page 8: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Glucose

2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

To recycle NADsacrifice energy (ATP)

Lactate

NADNADH+ H+

Acetyl-CoA

CoASH + NAD

CO2 + NADH + H+

3 ATPCoASH

Pi

Acetate

ADP

ATP

Page 9: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

GlucitolGlucoseGlucuronic acid

oxidized reduced

To generate ATP or to recycle NADRedox state of the carbon source matters

Page 10: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

NAD + CoASH

NADH + H+

NAD

Ethanol

NADH + H+

CoASH

Pi

Acetate

ADP

ATP

Acetyl-CoA

Glucuronic acidHighly oxidized

NADNADH + H+

GlucitolHighly reduced

NADNADH + H+

To generate ATP or to recycle NADRedox state of the carbon source matters

Page 11: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

EIIC

Glucose

CM

Glucose-6-P

EIIB

EIIB

EIIA

EIIA

HPr

HPr

EI

EI

PEP

Pyr

P

P

P

P

Getting Glucose InPhosphosugar Transferase System

PTS

Page 12: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Glucose

ATPADP

PDHC

Acetyl-CoA

CoASH + NAD

CO2 + NADH + H+

2 T3P

2 PEP

Pyruvate

ADPATP

2 ADP2 ATP

2 NAD2 NADH + 2 H+GAPDH

Glycolysis + PTS

pyruvate

PTS

Page 13: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Glucose

2 Acetyl-CoA

2 CoASH + 2 NAD

2 CO2 + 2 NADH + 2 H+

2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

6 NADH + 6 H+2 FADH2 + 2 H+2 ATP

18 ATP + 6 NAD4 ATP + 2 FAD

6 ATP + 2 NAD

6 ATP + 2 NAD

2 CoASH

38 ATP

Low glucoseSufficient oxygen

CO2 + NADH + H+

Glucose

Acetyl-CoA

CoASH + NAD2 Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

High glucoseSufficient oxygen

Aerobic fermentationBacterial Crabtree Effect

Overflow metabolismMixed acid fermentation

Acetate

ADPATP

CoASH

Lactate

NADNADH+ H+

Consequences of the PTS

Page 14: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

EIIC

Glucose

CM

Glucose-6-P

EIIB

EIIB

EIIA

EIIA

HPr

HPr

EI

EI

PEP

Pyr

P

P

P

P

6 NADH + 6 H+2 FADH2 + 2 H+2 ATP

Consequences of the PTSmechanism

Page 15: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

EIIC

Glucose

CM

Glucose-6-P

EIIB

EIIB

EIIA

EIIA

HPr

HPr

EI

EI

PEP

Pyr

P

P

P

P

CMAC

ATP cAMP CRP lac

Inducer exclusion

Lactose

More consequences of the PTS

Page 16: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Acetyl-CoA

Acetate

ADP

ATP

CoASH

Acetyl~P

Pi

Signaling by Acetate Fermentation

PTA

ACK RRRR~P

CellularProcesses

Page 17: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Acetyl-CoA

Acetate

ADP

ATP

CoASH

Acetyl~P

Pi

Signaling by Acetate Fermentation

An example

RcsBRcsB~P

Flagella

Capsule

Acetyl~P helps regulate the transition from free-swimming individual = planktonic

to sessile community = biofilms

Page 18: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Acetyl-CoA

Acetate

ADP

ATP

CoASH

Acetyl~P

Pi

Signaling by Acetate Fermentation

Another example

NtrCNtrC~P

Acetyl~P helps regulate the transition from free-swimming individual = planktonic

to sessile community = biofilms

glnAp2 Liao

Page 19: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Acetate Switch

Glucose

Pyruvate

2 ADP2 ATP

2 NAD2 NADH + 2 H+

Acetyl-CoA

CoASH + NAD

CO2 + NADH + H+

CoASH

Pi

Acetate

ADP

ATP

Acetyl~P Acetyl-AMPPPi

ATP

CoASH

AMPACS

ACS

ACS = acetyl-CoA synthetase

Page 20: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

CoASH

Ac~AMP

Acetyl-CoA

AMPAcs

ATP

PPi

AcsAcsAc ~

Inactive

PAT

glc

NAD+ NADH

GAPDH

TCANAD+

NADHMDH

Must regenerate NAD – How?

NAD+ NADHCobB

CobB = Sir2

Acs activitydepends on NAD

Acetate

Page 21: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Acetyl-CoA

NAD+ NADH

glcGAPDH

Lactate

Regenerating NAD

Pyr

LDH

Page 22: Glucose ATP ADP ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + T3P PEP Pyruvate ADP ATP ADP ATP NAD NADH + H + GAPDH -2 ATP +4 ATP -2 NAD -2 CoASH

Lactate

LDH

The Whole Shebang

Acetyl-CoAglc

NAD+ NADH

T3PGAPDH

TCANAD+

NADHMDH

NAD+

CobBNADH

crabtree

Ac~AMP

CoASH

AMPAcs

ATP

PPi

AcsAcsAcsAc ~

Inactive

PAT

CoASH

AMP

ATP

PPi

Ac~AMP

Acs

Ace

Pta-AckA pathway

ADP

ATP