1. 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
H2 O
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
H2 O ADP
Fructose-1,6-bis-P Fructose-1,6-bis-P
3P-Glyce G
E ROL rol
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 2 ADP
2.7.2.3 N 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+ ACETYL-CoA
Cytoplasmic Membrane
2GDP
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