GLUCONEOGENESIS & GLYCOLYSIS

High Blood Glucose

INSULIN
REACTANTS PRODUCTS REACTANTS PRODUCTS

Glucose GLUCOSE LIVER GLUCOSE Glucose

Pi Endoplasmic ATP
3.1.3.9 Reticulum 2.7.1.1
H2O
Glucose-6-P Glucose-6-P ADP

GLUCAGON 5.3.1.9 5.3.1.9

Fructose-6-P Fructose-6-P
Low Blood Glucose

Pi ATP
3.1.3.11 2.7.1.11
H2O ADP
Fructose-1,6-bis-P Fructose-1,6-bis-P
3P-Glyce G
OL rol
ER L
YC 4.1.2.13 4.1.2.13 SCLE
GL U MU
Di-OH-acetone-P G Di-OH-acetone-P
C (Glycerone-P)
5.3.1.1 (Glycerone-P) O L
Y GLUCOSE
N C
2Pi 3-P-Glyceraldehyde E 3-P-Glyceraldehyde
2 NAD+ O 2 NAD+
1.2.1.12 O L 1.2.1.12 2 Pi
2NADH+2H+ G 2NADH+2H+
2x 1,3-bis-P-Glycerate Y
2 ADP
E S 2x 1,3-bis-P-Glycerate
N 2 ADP
2.7.2.3 I 2.7.2.3
2 ATP E S 2 ATP
2x 3-P-Glycerate S 2x 3-P-Glycerate
I
5.4.2.1 S 5.4.2.1
2x 2-P-Glycerate 2x 2-P-Glycerate
4.2.1.11 4.2.1.11 2H2O
2H2O
2CO2 2x P-enolpyruvate 2x P-Enolpyruvate PYRUVATE
2 ADP
2 GDP
2.7.1.40
NADH+H+
4.1.1.32 2 ATP
2 GTP
2x Oxaloacetate 2x PYRUVATE 1.1.1.27
Glutamate 2NADH+2H+
2NADH+2H+ 2.6.1.21
1.1.1.27
1.1.1.37 2-Oxoglutarate
2 NAD+ NAD+
2 Aspartate 2 PEP LACTATE
2x Malate 2x LACTATE
2 Aspartate 2 PEP 2x PYRUVATE
2x Malate

Mitochondrial Outer Membrane

Mitochondrial Inner Membrane
2-Oxoglutarate 2 CO2
2NAD+ 2GDP ACETYL-CoA

Cytoplasmic Membrane
Mitochondrial Matrix
2.6.1.21
1.1.1.37 4.1.1.32
Glutamate
2NADH+2H+ 2GTP Citrate

Low Blood Glucose

Cytosol
Amino acid Oxaloacetate

2 ADP 2x Oxaloacetate 2x Oxaloacetate Malate

2 ATP 2 Pi Succinyl-CoA
2H2O
** 6.4.1.1
** ** 6.4.1.1 **
2CO2
ATP
2 PYRUVATE 2x PYRUVATE 2x Succinyl-CoA 2x PYRUVATE

2x PYRUVATE 2x Succinyl-CoA 2x PYRUVATE

Glutamate
5.4.99.2
2.6.1.21
2-Oxoglutarate 2 (S)-Methyl-
malonyl-CoA GL
2NADH+2H+ UC
5.1.99.1 1.1.1.27 AG
2NAD+ ON
2 (R)-Methyl-
malonyl-CoA ATP+CO2
VALINE 6.4.1.3 2x LACTATE
ADP+Pi CO
ISOLEUCINE RI C Y CLE
2x ALANINE METHIONINE 2x PROPIONYL-CoA

Low Blood Glucose

+ +
GLYCOLYSIS Glucose + 2ADP + 2Pi + 2NAD 2 Pyruvate + 2ATP + 2NADH + 2H + 2H2O
+ +
GLUCONEOGENESIS 2 Pyruvate + 4ATP + 2GTP + 2NADH + 2H + 6H2O Glucose + 4ADP + 2GDP + 6Pi + 2NAD
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 6ATP

Gluconeogenesis 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 cytosol

ENZYMES
1.1.1.27 Lactate dehydrogenase (only in cytosol) 2.7.1.40 Pyruvate kinase 5.1.99.1 Methylmalonyl-CoA epimerase
1.1.1.37 Malate dehydrogenase 2.7.2.3 Phosphoglycerate kinase 5.3.1.1 Triosephosphate isomerase
1.2.1.12 Glyceraldehyde-3-P dehydrogenase 3.1.3.9 Glucose-6-phosphatase 5.4.2.1 Phosphoglycerate mutase
2.7.1.1 Hexokinase 3.1.3.11 Fructose-bisphosphatase
2.7.1.30 Glycerolkinase 5.4.99.2 Methylmalonyl-Co mutase
4.1.1.32 Phosphoenolpyruvate carboxykinase
2.7.1.11 6-Phosphofructokinase 4.1.2.13 Fructose-bisphosphatealdolase 6.2.1.17 Propionate-CoA ligase
Liver Hexokinase is Hexokinase D (or IV)
(Often called Glucokinase)
4.2.1.11 Phosphopyruvate hydratase
6.4.1.1
6.4.1.3 ** Pyruvate carboxylase (only in matrix)
Propionyl-CoA carboxylase

Designed by Donald Nicholson c 2002 IUBMB