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 6C 2 x 3C 2x 2C Glycolysis

simplified Glucose 2 Acetyl-CoA 2 CoASH + 2 NAD 2 CO NADH + 2 H + 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H +

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

2 Acetyl-CoA 6 NADH + 6 H+ 2 FADH H+ 2 ATP 2 CoASH TCA / Respiration simplified 18 ATP + 6 NAD 4 ATP + 2 FAD

2 Acetyl-CoA 2 Acetate 2 ADP 2 ATP 2 CoASH 2 Acetyl~P PiPi Acetate Fermentation 2 Acetyl-CoA 2 Acetate 2 ADP 2 ATP 2 CoASH simplified An alternative

Glucose 2 Acetyl-CoA 2 CoASH + 2 NAD 2 CO NADH + 2 H + 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + Respiration 6 NADH + 6 H+ 2 FADH H+ 2 ATP 18 ATP + 6 NAD 4 ATP + 2 FAD 6 ATP + 2 NAD 2 CoASH 38 ATP Glucose 2 Acetyl-CoA 2 CoASH + 2 NAD 2 CO NADH + 2 H + 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + Fermentationversus 2 Acetate 2 ADP 2 ATP < 4 ATP 2 CoASH

Glucose 2 Acetyl-CoA 2 CoASH + 2 NAD 2 CO NADH + 2 H + 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + To recycle NAD sacrifice energy (ATP) 4 ATP 2 Lactate 2 NAD 2 NADH + 2 H + 2 ATP 2 NAD + 2 CoASH 2 NADH + 2 H + 2 NAD 2 Ethanol 2 NADH + 2H + 2 CoASH 2 P i 2 Acetate 2 ADP 2 ATP

Glucose 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + To recycle NAD sacrifice energy (ATP) Lactate NAD NADH + H + Acetyl-CoA CoASH + NAD CO 2 + NADH + H + 3 ATP CoASH PiPi Acetate ADP ATP

GlucitolGlucoseGlucuronic acid oxidizedreduced To generate ATP or to recycle NAD Redox state of the carbon source matters

NAD + CoASH NADH + H + NAD Ethanol NADH + H + CoASH PiPi Acetate ADP ATP Acetyl-CoA Glucuronic acid Highly oxidized NAD NADH + H + Glucitol Highly reduced NAD NADH + H + To generate ATP or to recycle NAD Redox state of the carbon source matters

EIIC Glucose CM Glucose-6-P EIIB EIIA HPr EI PEP Pyr P P P P Getting Glucose In Phosphosugar Transferase System PTS

Glucose ATP ADP PDHC Acetyl-CoA CoASH + NAD CO 2 + NADH + H + 2 T3P 2 PEP Pyruvate ADP ATP 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + GAPDH Glycolysis + PTS pyruvate PTSPTS

Glucose 2 Acetyl-CoA 2 CoASH + 2 NAD 2 CO NADH + 2 H + 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + 6 NADH + 6 H+ 2 FADH H+ 2 ATP 18 ATP + 6 NAD 4 ATP + 2 FAD 6 ATP + 2 NAD 2 CoASH 38 ATP Low glucose Sufficient oxygen CO 2 + NADH + H + Glucose Acetyl-CoA CoASH + NAD 2 Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + High glucose Sufficient oxygen Aerobic fermentation Bacterial Crabtree Effect Overflow metabolism Mixed acid fermentation Acetate ADP ATP CoASH Lactate NAD NADH + H + Consequences of the PTS

EIIC Glucose CM Glucose-6-P EIIB EIIA HPr EI PEP Pyr P P P P 6 NADH + 6 H+ 2 FADH H+ 2 ATP Consequences of the PTS mechanism

EIIC Glucose CM Glucose-6-P EIIB EIIA HPr EI PEP Pyr P P P P CM AC ATPcAMP CRPlac Inducer exclusion Lactose More consequences of the PTS

Acetyl-CoA Acetate ADP ATP CoASH Acetyl~P PiPi Signaling by Acetate Fermentation PTA ACK RR RR~P Cellular Processes

Acetyl-CoA Acetate ADP ATP CoASH Acetyl~P PiPi Signaling by Acetate Fermentation An example RcsB RcsB~P Flagella Capsule Acetyl~P helps regulate the transition from free-swimming individual = planktonic to sessile community = biofilms

Acetyl-CoA Acetate ADP ATP CoASH Acetyl~P PiPi Signaling by Acetate Fermentation Another example NtrC NtrC~P Acetyl~P helps regulate the transition from free-swimming individual = planktonic to sessile community = biofilms glnAp2 Liao

Acetate Switch Glucose Pyruvate 2 ADP 2 ATP 2 NAD 2 NADH + 2 H + Acetyl-CoA CoASH + NAD CO 2 + NADH + H + CoASH PiPi Acetate ADP ATP Acetyl~P Acetyl-AMP PP i ATP CoASH AMP ACS ACS = acetyl-CoA synthetase

CoASH Ac~AMP Acetyl-CoA AMP Acs ATP PP i Acs Ac ~ Inactive PAT glc NAD + NADH GAPDH TCA NAD + NADH MDH Must regenerate NAD – How? NAD + NADH CobB CobB = Sir2 Acs activity depends on NAD Acetate

Acetyl-CoA NAD + NADH glc GAPDH Lactate Regenerating NAD Pyr LDH

Lactate LDH The Whole Shebang Acetyl-CoA glc NAD + NADH T3P GAPDH TCA NAD + NADH MDH NAD + CobB NADH crabtree Ac~AMP CoASH AMP Acs ATP PP i Acs Ac ~ Inactive PAT CoASH AMP ATP PP i Ac~AMP Acs Ace Pta-AckA pathway ADP ATP