GLUCONEOGENESIS & GLYCOLYSISHigh Blood GlucoseINSULINREACTANTS PRODUCTS

Glucose Pi

GLUCOSE3.1.3.9

LIVER

GLUCOSE2.7.1.1

REACTANTS PRODUCTS

GlucoseATP

H2O

Endoplasmic Reticulum

Glucose-6-P5.3.1.9

Glucose-6-P5.3.1.9

ADP

GLUCAGON

Low Blood Glucose

Fructose-6-PPi H2O 3.1.3.11

Fructose-6-P2.7.1.11

ATP ADP

YC GL

ER

OL

3P-Glyce rol

Fructose-1,6-bis-P4.1.2.13

Di-OH-acetone-P 5.3.1.1 (Glycerone-P)2Pi 2 NAD+

3-P-Glyceraldehyde1.2.1.12

2NADH+2H+2 ADP 2 ATP

2x 1,3-bis-P-Glycerate2.7.2.3

2x 3-P-Glycerate5.4.2.1

2x 2-P-Glycerate2H2O 2CO2 2 GDP 2 GTP 4.1.1.32 4.2.1.11

G L U C O N E O G E N E S I S

Fructose-1,6-bis-P4.1.2.13

Di-OH-acetone-P G (Glycerone-P) L Y C 3-P-Glyceraldehyde O 2 NAD+ 1.2.1.12 2 Pi L 2NADH+2H+ Y 2x 1,3-bis-P-Glycerate S 2 ADP 2.7.2.3 I 2 ATP S 2x 3-P-Glycerate5.4.2.1

SCLE MU

GLUCOSE

2x 2-P-Glycerate4.2.1.11 2H2O 2 ADP 2 ATP

2x P-enolpyruvate 2x Oxaloacetate1.1.1.37

2x P-Enolpyruvate2.7.1.40

PYRUVATENADH+H+1.1.1.27

2NADH+2H+2 NAD+

Glutamate 2.6.1.21

2x PYRUVATE2 PEP

2NADH+2H+

2-Oxoglutarate

1.1.1.27

2x Malate 2x Malate2NAD+

2 Aspartate

NAD+

2x LACTATEMitochondrial Outer Membrane Mitochondrial Inner Membrane Mitochondrial Matrix

LACTATE

2 Aspartate2.6.1.21 Glutamate

2 PEP 2x PYRUVATEACETYL-CoAOxaloacetate Malate Succinyl-CoA Citrate4.1.1.32

2-Oxoglutarate

Amino acid 2 ADP 2 ATP 2H2O 2 Pi

2x Oxaloacetate

2x Oxaloacetate

**

6.4.1.1

**

** 6.4.1.1 **2x PYRUVATE

2CO2 2 PYRUVATE

2x PYRUVATE 2x Succinyl-CoA 2x PYRUVATEGlutamate 2.6.1.21

ATP

2x Succinyl-CoA5.4.99.2

2x PYRUVATE

2-Oxoglutarate

2NADH+2H+ 2NAD+

2 (S)-Methylmalonyl-CoA5.1.99.11.1.1.27

GL

UC

2 (R)-Methylmalonyl-CoA VALINE ISOLEUCINE METHIONINE

AG ON

ATP+CO2 6.4.1.3 ADP+Pi

2x LACTATE CO

2x ALANINE

2x PROPIONYL-CoA

RI C Y CLE

Low Blood Glucose

GLYCOLYSISGLUCONEOGENESIS

Glucose + 2ADP + 2Pi + 2NAD

++

Low Blood Glucose

2NADH+2H+

1.1.1.37

2 CO2 2GDP

Cytoplasmic Membrane

2GTP

2 Pyruvate + 2ATP + 2NADH + 2H

Cytosol

+

+ 2H2O+

Comparison of the two equations shows that: OXIDATION of 1 GLUCOSE to 2 PYRUVATE produces 2ATP whereas REDUCTION of 2 PYRUVATE to 1 GLUCOSE requires 4ATP + 2GTP To make GLUCONEOGENESIS thermodynamically possible requires the hydrolysis of the equivalent of 6ATPGluconeogenesis needs NADH for the reduction of 1,3-bis-P-glycerate to triose-P. For most precursors this is formed in the mitochondria and transported across the mitochondrial membrane via malate. Lactate is unique in that lactate dehydrogenase only occurs in the cytosol so that NADH is directly available in the cytosol for gluconeogenesis. However, the resulting pyruvate can only be converted into oxaloacetate within mitochondria since this is the only site of pyruvate carboxylase. The oxaloacetate so formed can then be transported into the cytosol by direct carboxylation to PEP or by transamination to aspartate in the mitochondria and then reverse transamination to oxaloacetate in the cytosolENZYMES Pyruvate kinase 5.1.99.1 Phosphoglycerate kinase 5.3.1.1 Glucose-6-phosphatase 5.4.2.1 Fructose-bisphosphatase 5.4.99.2 Phosphoenolpyruvate carboxykinase 6.2.1.17 Fructose-bisphosphatealdolase 6.4.1.1 Phosphopyruvate hydratase 6.4.1.3

2 Pyruvate + 4ATP + 2GTP + 2NADH + 2H + 6H2O

Glucose + 4ADP + 2GDP + 6Pi + 2NAD

1.1.1.27 Lactate dehydrogenase (only in cytosol) 1.1.1.37 Malate dehydrogenase 1.2.1.12 Glyceraldehyde-3-P dehydrogenase 2.7.1.1 Hexokinase 2.7.1.30 Glycerolkinase 2.7.1.11 6-Phosphofructokinase Liver Hexokinase is Hexokinase D (or IV) (Often called Glucokinase)

2.7.1.40 2.7.2.3 3.1.3.9 3.1.3.11 4.1.1.32 4.1.2.13 4.2.1.11

**

Methylmalonyl-CoA epimerase Triosephosphate isomerase Phosphoglycerate mutase Methylmalonyl-Co mutase Propionate-CoA ligase Pyruvate carboxylase (only in matrix) Propionyl-CoA carboxylase

Designed by Donald Nicholson

c 2002 IUBMB