Core Metabolic Roadmap

How to get the molecules that are needed, when they’re needed.
Key:  inhibits multiple steps reversible
Glucose metabolism
hexokinase Glucose
(isoform called glucose
glucokinase in liver) ATP Pi 6-phosphatase
Pentose Phosphate Pathway G6P (but not ADP H2O (mainly in liver)
for glucokinase)
Oxidative phase Glycogen metabolism
6-phosphogluconate glucose 6-phosphate dehydrogenase Glucose 6-Phosphate UDP-glucose
dehydrogenase   NADPH

phosphogluco- glycogen synthase
pyrophosphorylase  glucagon
NADP +
phospho-
Non-oxidative phase mutase UTP PPi
NADPH gluconolactonase NADPH glucose
UDP
CO2 H+ H2O
Ribulose
NADP+
6-Phospho- 6-Phospho- isomerase Glucose UDP-glucose
Glycogen
5-Phosphate gluconate gluconolactone 1-phosphate
glycogen phosphorylase
Fructose 6-Phosphate insulin   
phosphofructokinase 2
ribose 5-phosphate ribulose 5-phosphate
 glucagon
isomerase 3-epimerase phosphofructokinase 1
ATP Pi ATP
F26BP, AMP, ADP    


ADP H2O ADP
ATP, citrate         
Ribose Xylulose fructose 1,6- Pi      
5-Phosphate 5-Phosphate bisphosphatase 1 H2O
 fructose Fructose
F26BP, AMP 2,6-bisphosphatase 2
   insulin, X5P* 2,6-Bisphosphate
Fructose 1,6-Bisphosphate
carbon scrambling via
fructose glycerol 3-phosphate
transaldolase and transketolase
bisphosphate dehydrogenase
Nucleotides aldolase NADH NAD+
Glyceraldehyde + Dihydroxyacetone- glycerol kinase
cGPDH
3-Phosphate phosphate Glycerol
Glycerol
glyceraldehyde NAD + Pi + mGPDH 3-phosphate ADP
triose phosphate ATP
3-phosphate NADH
isomerase FADH2 FAD
dehydrogenase
uses NAD+/NADH in cytoplasm,
DNA, RNA, coenzymes 1,3-Bisphosphoglycerate FAD/FADH2 in mitochondria
phosphoglycerate kinase
ADP
ATP

3-Phosphoglycerate
phosphoglycerate mutase

Caution: The steps of

glycolysis & gluconeogenesis
from G3P to pyruvate occur 2-Phosphoglycerate
2X per glucose molecule! enolase

Phosphoenolpyruvate
CO2
pyruvate kinase ADP GDP PEP
F16BP ATP GTP carboxykinase
malate dehydrogenase
acetyl-CoA, ATP, NADH,
long chain fatty acids, Oxaloacetate Malate
alanine, glucagon (in liver) ADP + Pi
pyruvate
ATP carboxylase NADH NAD+
HCO3 -
acetyl-CoA

Pyruvate alanine transaminase

pyruvate glutamate
carboxylase α-ketoglutarate
lactate dehydrogenase pyruvate
malic acetyl-CoA Lactate fermentation is
enzyme
NADH dehydrogenase NAD+ Alanine
especially important under NAD+
CO2 acetyl-CoA, ATP,
limiting oxygen conditions.
NADH, fatty acids
NADH Triacylglycerols
CO2
CO2
ATP Lactate AMP, CoA, (TAGs) Phospholipids
Urea ADP + Pi citrate synthase NAD+, Ca2+ Ketone bodies
NADPH succinyl-CoA, ATP, NADH, citrate
urea
ADP Acetyl-CoA thiolase
NADP+
cycle
aspartate transaminase
α-ketoglutarate glutamate CoA mitochondrial β-oxidation
glycerol
Acetoacetyl-CoA Fatty acids
Aspartate AST Oxaloacetate citrate Citrate citrate lyase malonyl-CoA 2 NADP+
synthase
NADH 2 NADPH
MDH aconitase ATP cytoplasmic acetyl-CoA carboxylase
malate ADP + Pi citrate, palmitoyl-CoA
NAD+ dehydrogenase Isocitrate Acetyl-CoA Malonyl-CoA
oxaloacetate
Malate isocitrate HCO3-
NAD+ ATP ADP + Pi
dehydrogenase
fumarase NADH
Citric acid cycle - aka H2O
ATP
ADP, Ca2+
thiolase

tricarboxylic acid cycle

CO2 Lipid Metabolism
Fumarate α-ketoglutarate Acetoacetyl-CoA
Acetyl-CoA can’t cross the
(TCA) or Krebs cycle succinate
dehydrogenase
α-ketoglutarate
CoA HMG-CoA acetyl-CoA mitochondrial membranes, so
dehydrogenase various
Different intermediates can be added & synthase CoA separate pools of it are used in the
FADH2 CII (CII of the ETC) succinyl-CoA, NAD + transaminases
mitochondria (where the TCA and
removed for/from the metabolism of NADH or glutamate
succinyl-CoA Ca2+ NADH HMG-CoA fatty acid breakdown occur) and
various molecules (e.g. amino acids). FAD dehydrogenase
Succinate synthetase the and in the cytoplasm (where
Malate can be removed from mitochondria & CO2 lipids are synthesized).
converted to oxaloacetate (by cytosolic MDH) Q
Succinyl-CoA
for glucose synthesis. QH2
CoA
ADP + Pi
Citrate can be removed from mitochondria, & GTP
GDP + Pi
ATP Glutamate Cholesterol Steroids
HCO3-
converted into acetyl-CoA (& oxaloacetate) by (ADP/ATP in
citrate lyase for lipid synthesis. some isoforms) Propionyl-CoA cytosolic oxidative
& acetyl-CoA Glycerol-3-phosphate shuttle
β-oxidation reactions
Many of the above reactions take place in the cytosol (e.g. NADH
NAD+
glycolysis), the mitochondria (e.g. the TCA cycle), or either one. Odd-chain Malate-aspartate shuttle +H
The ETC, however, has strict localization in the inner fatty acids cMDH = cytosolic cGPDH = cytosolic glycerol 3-phosphate
malate dehydrogenase cGPDH dehydrogenase (NAD+-linked)
mitochondrial membrane (IMM).
NADH & FADH2 aspartate oxaloacetate
aspartate Dihydroxyacetone Glycerol
Reducing equivalents from NADH generated in the cytoplasm transaminase* NADH phosphate (DHAP) 3-phosphate
must be shuttled into the mitochondrial matrix (e.g. via the cMDH +H H
H
malate-aspartate shuttle or the glycerol-3-phosphate shuttle). AST
4H
NAD+ 4H 2H H
α-ketoglutarate glutamate FADH2 FAD
malate
intermembrane H H cytC
Electron transport chain (ETC) & space aspartate- malate-
mGPDH
α-ketoglutarate Q
oxidative phosphorylation (oxphos) glutamate
antiporter antiporter CIV
CI CII CIII
mitochondrial malate CV
The passing of electrons powers the pumping of matrix α-ketoglutarate glutamate NAD +
1/2 O2 +
protons, which creates a proton gradient that powers the H2O
mMDH FADH2 FAD + H H H H
production of ATP by ATP synthase (CV).
AST mitochondrial NADH
malate
ADP H
+H NAD+ + Pi ATP
aspartate dehydrogenase
transaminase*
fumarate succinate It “costs” ~4 H+
aspartate oxaloacetate CII = succinate per ATP made.
dehydrogenase of (~3 used directly by CV
various mitochondrial the TCA (ATP synthase) and 1
for bringing in a Pi)
oxidative reactions
mGPDH = mitochondrial
*aspartate transaminase is aka aspartate aminotransferase and glycerol 3-phosphate
glutamic-oxaloacetic transaminase (GOT) dehydrogenase (FAD-linked)
DOI: 10.5281/zenodo.13338217