Pyruvate kinase
PKM
Pyruvate kinase
isozymes R/L
Solute carrier
family 2,
facilitated
glucose
transporter
member 2
Mitochondrial
pyruvate
carrier 1
Monocarboxylate
transporter 1
Neutral amino
acid
transporter
B(0)
Mitochondrial
citrate
transport
protein
Hexokinase-2
Glucose-6-
phosphate
isomerase
6-
phosphofructokinase,
liver type
Fructose-
bisphosphate
aldolase B
Glyceraldehyde-
3-phosphate
dehydrogenase
Phosphoglycerate
kinase 1
Phosphoglycerate
mutase 2
Alpha-enolase
Pyruvate
carboxylase,
mitochondrial
Pyruvate
dehydrogenase
complex
Citrate
synthase,
mitochondrial
L-lactate
dehydrogenase
A-like 6A
Aconitate
hydratase,
mitochondrial
Isocitrate
dehydrogenase
[NAD] subunit
alpha,
mitochondrial
Isocitrate
dehydrogenase
[NAD] subunit
beta,
mitochondrial
Isocitrate
dehydrogenase
[NAD] subunit
gamma,
mitochondrial
Oxoglutarate
dehydrogenase
complex
Succinyl-CoA
ligase
Succinate
dehydrogenase
Fumarate
hydratase,
mitochondrial
Malate
dehydrogenase,
cytoplasmic
Glutamate
dehydrogenase
1,
mitochondrial
Glutaminase
liver isoform,
mitochondrial
Transaldolase
Transketolase
Ribose-5-
phosphate
isomerase
6-
phosphogluconolactonase
Glucose-6-
phosphate
isomerase
Glucose-6-
phosphate
1-dehydrogenase
6-
phosphogluconate
dehydrogenase,
decarboxylating
Cytoplasmic
aconitate
hydratase
Isocitrate
dehydrogenase
[NADP]
cytoplasmic
D-Glucose
D-Glucose
Pyruvic acid
Pyruvic acid
L-Lactic acid
L-Glutamine
L-Glutamine
L-Glutamine
Citric acid
Citric acid
ATP
Glucose 6-phosphate
ADP
Fructose 6-phosphate
ATP
Fructose 1,6-bisphosphate
ADP
D-Glyceraldehyde 3-phosphate
NAD
Glyceric acid 1,3-biphosphate
NADH
ADP
3-Phosphoglyceric acid
ATP
2-Phospho-D-glyceric acid
Phosphoenolpyruvic acid
H2O
ATP
ADP
ATP
HCO3-
ADP
Pi
Oxalacetic acid
CoA
NAD
Acetyl-CoA
CO2
NADH
H2O
CoA
NAD
NADH
Isocitric acid
NAD
Oxoglutaric acid
CO2
NADH
NAD
CoA
Succinyl-CoA
NADH
CO2
Pi
GDP
Succinic acid
CoA
GTP
Q
FAD
Fumaric acid
QH2
FADH2
L-Malic acid
H2O
NAD
NADH
L-Glutamic acid
H2O
NH3
H2O
NH3
D-Erythrose 4-phosphate
D-Sedoheptulose 7-phosphate
D-Ribose 5-phosphate
Xylulose 5-phosphate
D-Ribulose 5-phosphate
6-Phosphonoglucono-D-lactone
H2O
6-Phosphogluconic acid
β-D-Glucose 6-phosphate
NADP
NADPH
H+
NADP
CO2
NADPH
Isocitric acid
NADP
Oxoglutaric acid
NADPH
CO2
Magnesium
Potassium
Magnesium
Magnesium
Biotin
Manganese
Thiamine
pyrophosphate
Lipoamide
FAD
4Fe-4S
Magnesium
Thiamine
pyrophosphate
Lipoamide
FAD
Magnesium
Thiamine
pyrophosphate
4Fe-4S
Magnesium
L-Lactic acid
Lactate shuttle
Pentose Phosphate Shunt
Citric Acid Cycle
Inner Mitochondrial Membrane
Outer Mitochondrial Membrane
Mitochondrion
Cytosol
Glycolysis
Phosphoenolpyruvic acid
Pyruvic acid
L-Lactic acid
2-Phospho-D-glyceric acid
3-Phosphoglyceric acid
Glyceric acid
1,3-biphosphate
D-Glyceraldehyde 3-phosphate
Fructose 6-phosphate
Fructose 1,6-bisphosphate
Pyruvate kinase PKLR
L-lactate dehydrogenase
Pyruvate kinase PKM
The production of ATP
through the Citric Acid
Cycle is limited to 1%.
Lactic acid accumulation
leads to a low pH
microenvironment
The large lactate efflux
leads to activation of many
factors in adjacent cells
involved in angiogenesis.
Low conversion of PEP into
pyruvate can lead to the
accumulation of upstream
glycolytic intermediates.
Intermediates are used for
synthesis of nucleotides,
amino acids and fatty acids
required in proliferation.
Angiogenesis
Proliferation
Cancer Cell
Nucleus