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Metabolic Pathway Map

NUTR 412: Advanced Human Metabolism

Grant Buckley

Pyruvate

NAD+

CoASH

Pyruvate Dehydrogenase

NADH + H+

CO2

CoASH

Galactose

Galactose

Glycogenesis

Glycogenolysis

Glycogenesis

Cell Membrane

Glycolysis

Cell Membrane

Hexose Monophosphate Shunt

ATP

Galactokinase

ATP

ADP

Galactokinase

ADP

Galactose-1-P

Glycogen

Galactose-1-P

Glycogen

ADP

ATP

ADP

Glucose

Glucose-6-P

Glucose-1-P

Hexokinase / Glucokinase

Glucose

Glucose-6-P

Glucose-1-P

Hexokinase / Glucokinase

Glucose Phosphate Isomerase

Glucose Kinase Isomerase

Fructose-6-P

ADP

ATP

Hexose Monophosphate Shunt

Fructose-6-P

ATP

Phosphofructokinase

ATP

ADP

Phosphofructokinase

ADP

Fructose-1,6 bis P

ADP

ATP

ADP

ATP

Fructose-1,6 bis P

Fructose

Fructose-1-P

Fructose-1-P

Fructose

Fructokinase

DHAP

G-3-P

DHAP

G-3-P

Pi

NAD+

Pi

NAD+

NADH + H+

NADH + H+

Glycolysis

1,3 bis P Glycerate

1,3 bis P Glycerate

ADP

ADP

ATP

ATP

3-P-Glycerate

3-P Glycerate

2-P-Glycerate

2-P Glycerate

PEP

NADH + H+

NAD+

ADP

PEP

ADP

ATP

NADH + H+

NAD+

Pyruvate

Lactate

(anaerobic)

ATP

Alanine-Glucose Cycle

Pyruvate

Lactate

(anaerobic)

Mitochondrial Oxidation (aerobic)

Mitochondrial Oxidation (aerobic)

Gluconeogenesis

TCA Cycle

Alanine-Glucose Cycle

Glycogensis

Glycogenesis

ADP

ATP

Alpha-D-Glucose

Glucose-1-P

Glucose-6-P

ATP

ADP

Phosphoglucomutase

UTP

Glucose-6-P

Alpha-D-Glucose

Glucose-1-P

Glycolysis

Phosphoglucomutase

UTP

Glycogenin Primer

PPI

UDP-Glucose

Glycogen

(unbranched)

PPI

Glycogenin Primer

Glycogen (unbranched)

UDP-Glucose

Branching Enzyme

Glycogen (branched)

Glycolysis

Glycogenolysis

Glycogenesis

Muscle and Liver

Non-reducing end

of glycogen chain

Glucose-1-P

Non-Reducing end of the glycogen chain

Glucose-1-P

Glycogen Phosphorylase

Glycogen Phosphorylase

Glycolysis

(HPO4)2-

(HPO4)2-

Glucose-6-P

Glucose-6-P

Glycogenolysis

Glycogenolysis

Pi

Kidney or Liver

Glucose

Liver or Kidney

Glucose

Fate of Amino Acid Skeleton

Gluconeogenesis

G6P

F6P

Glucose

Glucose

G6P

F6P

Alanine-Glucose Cycle

FBP

Glycerol

FBP

Glycerol

G3P

DHAP

Cytsol

G3P

DHAP

BPG

3PG

Gluconeogenesis

BPG

3PG

2PG

Oxaloacetate

TCA Cycle

Oxaloacetate

2PG

Cytosol

PEP

Malate

Malate

Mitochondria

PEP

Mitochondria

Malate

Fumarate

Fumarate

Amino Acids

Glycolysis

Lactate

Malate

Succinate

Succinate

Amino Acids

Lactate

Oxaloacetate

Succinyl-CoA

Succinyl-CoA

Oxaloacetate

Alpha-ketoglutarate

Pyruvate

Alpha-

Ketoglutarate

Pyruvate

Urea Cycle

Pyruvate

Acetyl-CoA

Citrate Synthase

Fatty Acid Synthesis

Oxaloacetate

Gluconeogenesis

Oxaloacetate

Malate Dehydrogenase

CoASH

H2O

NADH + H+

Urea Cycle

NAD+

Citrate

Malate

Citrate

Malate

NAD+

Fumarase

Aconitase

Fumarase

Aconitase

H2O

TCA Cycle

TCA Cycle

Urea Cycle

Isocitrate

Fumarate

Isocitrate

Fumarate

NAD+

NAD+

FADH2

FADH2

NADH + H+

FAD

Isocitrate Dehydrogenase

Succinate Dehydrogenase

FAD

NADH + H+

Succinate Dehydrogenase

Isocitrate Dehydrogenase

CO2

Alpha-ketoglutarate

Succinate

Alphaketoglutarate

CO2

NAD+

NAD+

Succinyl-CoA Synthetase

CoASH

P

NADH + H+

NADH + H+

P

CoASH

Nucleoside Diphosphate Kinase

Succinyl-CoA

Alpha-Ketoglutarate Dehydrogenase

GTP

Alphaketoglutarate Dehydrogenase

GTP

GDP

CO2

GDP

CO2

ADP

Nucleoside Diphosphate Kinase

ATP

Hexosemonophosphate Shunt

Hexosemonophosphate Shunt

Oxidative Stage

Nonoxidative Stage

Oxidative Stage

Nonoxidative Stage

Hexose Phosphate Isomerase

Glucose-6-P

Fructose-6-P

Hexose Phosphate Isomerase

NADP+

Glucose-6-P

Fructose-6-P

G-6-PD

Glyceraldehyde-3-phosphate

NADP+

NADHP + H+

Glyceraldehyde-3-phosphate

G-6-PD

NADPH + H+

Glycolysis

6-phosphoglucolactone

Transketolase

6-phosphoglucolactone

Glucolactonase

These are Reversible

Transaldolase

Glucolactonase

Transaldolase

6-phosphogluconate

NADP+

6-phosphogluconate

Transketolase

NADP+

Glycolysis

Transketolase

NADPH + H+

6-GDP

NADPH + H+

6-PGD

CO2

Epimerase

D-xylose

5-phosphate

D-ribose

5-phosphate

D-ribulose

5-phosphate

D-ribulose

Epimerase

D-ribose

5-phosphate

D-xylulose

5-phosphate

5-phosphate

Phosphopentose Isomerase

Fatty Acid Synthesis

TCA Cycle

Fatty Acid Synthesis

Mitochondria

Cytosol

Citrate

Acetyl-CoA Oxaloacetate

Cytosol

Mitochondria

Acetyl-CoA Oxaloacetate

Citrate

CoA

Citrate

Oxaloacetate + Acetyl-CoA

Citrate Lyase

CoA

ATP

ADP + Pi

Oxaloacetate + Acetyl-CoA

Citrate

CO2

Citrate Lyase

Biotin

ATP

Malonyl-CoA

Acetyl-CoA

ADP + Pi

Acetyl-CoA Carboxylase

CO2

Biotin

ATP

Acetyl-CoA

Malonyl-CoA

ADP + Pi

Acetyl-CoA Carboxylase

ATP

ADP + Pi

Acetyl-CoA + HS ~~ Condensing Enzyme

Acetyl-S ~~ Condensing Enzyme

Malonyl S ~ ACP

Malonyl-CoA + HS ~ ACP

Acetyl S ---- Condensing Enzyme

Acetyl-CoA + HS ---- Condensing Enzyme

Malonyl S -- ACP

Malonyl-CoA + HS -- ACP

Elongation

FAD

Beta Oxidation

Palmitoyl-CoA

Acetyl-CoA

FADH2

Electron Transport Chain

Acetyl-CoA

TCA Cycle

Acyl-CoA Dehydrogenase

FADH2

Electron Transport Chain

Acyl-CoA Dehydrogenase

TCA Cycle

Acyl-CoA + Acetyl-CoA

TCA Cycle

Acyl-CoA + Acetyl-CoA

CO2

1.5 ATP's

CO2

1.5 ATP's

Enoyl-CoA

H2O

Acetyltransferase

(Thiolase)

Acetyltransferase (Thiolase)

10 ATP's

H2O

CoA

10 ATP's

CoA

H2O

Beta-Oxidation

Enoyl-CoA Hydratase (Crotonase)

Beta-Ketoacyl-CoA

Enoyl-CoA Hydratase (Cronotase)

Beta-Ketoacyl-CoA

2.5 ATP's

Beta-Hydroxyacyl-CoA Dehydrogenase

NADH + H+

Beta-Hydroxyacyl-CoA Dehydrogenase

Beta-Hydroxyacyl-CoA

NADH + H+

Electron Transport Chain

NAD+

2.5 ATP's

Electron Transport Chain

NAD+

2 ATP

NH3

Carbamoyl Phosphate Synthetase

CO2

2ADP + Pi

Carbamoyl-PO4

TCA Cycle

Urea Cycle

2 ADP + Pi

Ornithine Transcarbamoylase

Carbamoyl Phosphate Synthetase

Carbamoyl-PO4

Carbamoylphosphate Synthetase

2 ATP

NH3

Carbamoylphosphate

Synthetase

CO2

Citrulline

Ornithine

Citrulline

Ornithine

Urea

Oxaloacetate

Aspartate

Arginase

AST

Alanine-Glucose Cycle

Urea Cycle

PLP

Aspartate

Oxaloacetate

AST

Alpha-Keto-Glutarate

Glutamate

Arginine

PLP

Arginine

ALT

Alpha-Keto-Glutarate

Glutamate

PLP

ALT

ATP

Fumarate

Pyruvate

Alanine

TCA Cycle

Fumarate

PLP

ATP

Alanine

Argininosuccinate Synthetase

Argininosuccinase

Pyruvate

Argininosuccinase

Argininosuccinate Synthetase

Arginiosuccinate

AMP + PPi

Gluconeogensis

AMP + PPi

Fate of Amino Acid Skeleton

Fate of Amino Acid Skeleton

Ala

Gly

Ser

Cys

Trp

Thr

Glucose

Ile

Leu

Lys

Thr

Trp

Leu

Tyr

Phe

Phosphoenol Pyruvate

Glucose

Ala

Gly

Ser

Cys

Trp

Thr

Pyruvate

Ile

Leu

Lys

Thr

Trp

Oxaloacetate

Ketones

Acetyl-CoA

Acetoacetate

Asp

Asn

Leu

Tyr

Phe

Phosphoenol Pyruvate

(Malate)

Pyruvate

Oxaloacetate

Acetoacetate

Acetyl-CoA

Ketones

Asp

Asn

Phe

Tyr

Asp

Citrate

Fumarate

Fatty Acids

Fatty Acids

(Malate)

Succinyl-CoA

Val

Ile

Met

Thr

Phe

Tyr

Asp

Citrate

Arg

His

Pro

Glu

Gln

Val

Ile

Met

Thr

Fumarate

Arg

His

Pro

Glu

Gln

Alpha-Ketoglutarate

Succinyl-CoA

Alpha-Ketoglutarate

Gluconeogenesis

Alanine-Glucose Cycle

Glycogenesis

Alanine-Glucose Cycle

Gluconeogenesis

Liver

Muscle

Blood

Muscle

Liver

Gluconeogenesis

Glucose

Glycogen

Glucose

6-PO4

Glucose

Glycogen

6-PO4

Glycolysis

Gluconeogensis

Glycolysis

Gluconeogenesis

Alanine

Pyruvate

Alanine

Pyruvate

Alanine

Urea Cycle

Alpha-Ketoglutarate

Glutamate

Alpha-Ketoglutarate

Glutamate

Alpha-Ketoglutarate

Glycolysis

Deamination

Alpha-Ketoisocaproate

Muscle

NH3

Alpha-Ketoisocaproate

Muscle

Urea

Micronutrient Co-Enzymes

Transketolase - Thiamin (Vitamin B1)

FAD - Riboflavin (Vitamin B2)

NAD - Niacin (Vitamin B3)

Pyridoxal 5'-phosphate [PLP] (Vitamin B6)

CoA - Pantothentic Acid

Micronutrient Co-Enzymes

Transkeletolase - Thiamin (Vitamin B1)

FAD - Riboflavin (Vitamin B2)

NAD - Niacin (Vitamin B3)

Pyridoxal 5'-phosphate [PLP] (Vitamin B6)

CoA - Pantothenic Acid

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