Alcohol Metabolism
•Cellular processing
•Pathway perturbations
•Malate-aspartate shuttle
•Glycerol-3-phosphate shuttle
Eric Niederhoffer
SIU-SOM
Oh my!
Now what?
Cellular Processing
EtOH
Peroxisome
Cytosol
H2O2
CAT
H2O
ER
O2
Aminotriazole
NADPH
NAD+
MEOS
P450
ADH
Pyrazole
NADH
NADP+
Acetaldehyde
NAD+
Mitochondrion
AlDH
NADH
Disulfiram Chlorpropamide
(antabuse)
(diabetes)
Acetate
Extra-hepatic tissue
Pathway Perturbations
Glc
G6Pase
GK
G6P
Cytosol
F6P
F16BPase
PFK
Ala
F16BP
PEPCK
OAA
PEP
NAD+
NAD+
ALT
AST
PK
MDH
LDH
Lactate
Pyr
NADH
NADH
Malate
Asp
Malate
PDH
NADH
PC
Acetyl CoA
NAD+
MDH
OAA
NADH
MDH
OAA
NADH
-Ox
FA
NADH
Cit
Malate
ICit
Mitochondrion
NAD+
Fum
NAD+
aKGDH
Suc
S CoA
aKG
NADH
IDH
NADH
Malate-Aspartate Shuttle
(liver, kidney, heart)
IMS
IM
Matrix
CI
GT
Asp
Asp
aKG
aKG
AST
AST
Glu
Glu
OAA
OAA
NADH
NADH
MDH
MDH
NAD+
NAD+
Mal
MaT
Mal
Glycerol-3-Phosphate
Shuttle
(skeletal muscle, brain)
IMS
NAD+
IM
Matrix
G3P
FAD
G3PDH
NADH
DHAP
FADH2
CIII
Q
Review Questions

How is ethanol detoxified
(enzymes, cofactors, products,
location)?

Which metabolic pathways are
affected by alcohol-derived NADH
(enzymes, metabolites)?

What are useful (important) clinical
markers?

How does the cell process NADH?