A 38-year-old woman is brought to the physician because of frequent falls, increasing confusion, and incontinence How does ethanol ingestion cause nutrition problems? Eric Niederhoffer SIU-SOM Alcohol Metabolism and Effects • Cellular processing • Pathway perturbations • Malate-aspartate shuttle • Glycerol-3-phosphate shuttle Cellular Processing EtOH Peroxisome Cytosol H2O2 O2 CAT H2O ER Aminotriazole NADPH NAD+ MEOS P450 ADH Pyrazole NADH NADP+ Acetaldehyde NAD+ Mitochondrion AlDH NADH Disulfiram Chlorpropamide (antabuse) (diabetes) Acetate Extra-hepatic tissue Pathway Perturbations Gluconeogenesis G6Pase Glc Glycolysis GK G6P Cytosol F6P F16BPase PFK Ala F16BP Asp PEPCK OAA PEP NAD+ NAD+ ALT AST PK MDH LDH Lactate Pyr NADH NADH Malate MDH Malate NADH OAA PDH β-Ox NADH PC Acetyl CoA FA NAD+ NADH MDH OAA Cit NADH Malate ICit Mitochondrion NAD+ Fum NAD+ αKGDH Suc S CoA αKG NADH ICDH NADH Malate-Aspartate Shuttle (liver, kidney, heart) IMS IM Matrix CI GT Asp Asp αKG αKG 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?