Fig. S1. Summary of the altered metabolism pathways in alcoholic fatty liver disease using MetPA analysis (panel A).

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1 Electronic Supplementary Material (ESI) for Molecular BioSystems. This journal is The Royal Society of Chemistry 2015 Fig. S1. Summary of the altered metabolism pathways in alcoholic fatty liver disease using MetPA analysis (panel A). The map was generated using the reference map by KEGG. CO represents entry number of compound. Pentose and glucuronate interconversions (panel B); Starch and sucrose metabolism (panel C); Cysteine and methionine metabolism (panel D) (details in Table S1). 1

2 Fig. S2. ICA analysis of isobaric tags for relative and absolute quantitation (itraq) proteome data of alcoholic fatty liver disease. Green, control; red: 12W; 2

3 Fig. S3. An updated view of the pathway and signaling network by Gene Ontology. The differentially expressed proteins were classified among three categories: biological process (A), molecular function (B), and cellular component (C). 3

4 Fig.S4 Pathogenic mechanisms of alcoholic liver disease proposed based in animal models evidence, and p53 signaling pathway 4

5 Supplementary table 1. Result from ingenuity pathway analysis with MetPA. No. Pathway Name Total Expected Hits Raw p Impact 1 Starch and sucrose metabolism Riboflavin metabolism Nicotinate and nicotinamide metabolism Pentose and glucuronate interconversions Cysteine and methionine metabolism Arginine and proline metabolism minoacyl-trna biosynthesis Note: Total is the total number of compounds in the pathway; the Hits is the actually matched number from the user uploaded data; the Raw p is the original p value calculated from the enrichment analysis; the Impact is the pathway impact value calculated from pathway topology analysis. 5

6 Supplementary Table 2. Differentially expressed proteins in alcoholic fatty liver disease identified by itraq. No. Accession(gi) Description Score Coverage Proteins Unique Peptides PSMs AAs MW calc. C/M Peptides [kda] pi 1 P49000 Muellerian-inhibiting factor % Q68FQ0 T-complex protein 1 subunit epsilon % Q80T18 Glia maturation factor gamma % Q9JLT0 Myosin % P protein eta % Q920G0 Src kinase-associated % phosphoprotein 2 7 P58775 Tropomyosin beta chain % Q63083 Nucleobindin % Q9JK11 Reticulon % Q00715 Histone H2B type % P50115 Protein S100-A % Q kda heat- and acid-stable % phosphoprotein 13 Q5RKI1 Eukaryotic initiation factor 4A-II % P60901 Proteasome subunit alpha type % P50116 Protein S100-A % P06759 Apolipoprotein C-III % P31394 Vitamin K-dependent protein C % P28480 T-complex protein 1 subunit alpha % P18418 Calreticulin % P01015 Angiotensinogen % P24594 Insulin-like growth factor-binding % protein 5 22 P15978 Class I histocompatibility antigen, % Non-RT1.A alpha-1 chain 23 Q9WV63 Kinesin-like protein KIF2A % P85108 Tubulin beta-2a chain % P08932 T-kininogen % Q9WUK5 Inhibin beta C chain % Q62975 Protein Z-dependent protease % inhibitor 28 Q5M8C6 Fibrinogen-like protein % Q9Z244 GMP reductase % P07756 Carbamoyl-phosphate synthase % [ammonia], mitochondrial 31 P04276 Vitamin D-binding protein % P62804 Histone H % P protein beta/alpha % P25236 Selenoprotein P % Q8R2H5 Phosphatidylinositol-glycan-specific % phospholipase D 36 P24090 Alpha-2-HS-glycoprotein % P04041 Glutathione peroxidase % P26644 Beta-2-glycoprotein % P62630 Elongation factor 1-alpha % Q9EQV9 Carboxypeptidase B % P23593 Apolipoprotein D % Q63276 Bile acid-coa:amino acid N % acyltransferase 43 Q63520 Synaptonemal complex protein % P55314 Complement component C8 beta % chain 45 P05545 Serine protease inhibitor A3K % P04639 Apolipoprotein A-I % Q9QX79 Fetuin-B % P55159 Serum paraoxonase/arylesterase % P21744 Insulin-like growth factor-binding % protein 4 50 P23680 Serum amyloid P-component % O35460 Angiopoietin % Q6IFU7 Keratin, type I cytoskeletal % P48032 Metalloproteinase inhibitor % P35572 Insulin-like growth factor-binding % protein 6 55 Q64640 Adenosine kinase % P02091 Hemoglobin subunit beta % Q4FZU2 Keratin, type II cytoskeletal 6A % P10760 Adenosylhomocysteinase % P20762 Ig gamma-2c chain C region % P15473 Insulin-like growth factor-binding % protein 3 61 Q6IG04 Keratin, type II cytoskeletal % Q6IG02 Keratin, type II cytoskeletal % epidermal 63 Q4KM35 Proteasome subunit beta type % Q09429 ATP-binding cassette transporter % sub-family C member 8 65 Q63484 RAC-gamma serine/threonineprotein kinase % P59996 Proprotein convertase %

7 subtilisin/kexin type 9 67 P55797 Apolipoprotein C-IV % P01836 Ig kappa chain C region, A allele % P09034 Argininosuccinate synthase % P ketoacyl-CoA thiolase B, % peroxisomal 71 P10354 Chromogranin-A % Q6IMF3 Keratin, type II cytoskeletal % Q6IG03 Keratin, type II cytoskeletal % P05964 Protein S100-A % P08025 Insulin-like growth factor I % Q6IFW6 Keratin, type I cytoskeletal % P oxo-5-beta-steroid % dehydrogenase 78 P18757 Cystathionine gamma-lyase % Q6P6Q2 Keratin, type II cytoskeletal % Q9QZR6 Septin % P06757 Alcohol dehydrogenase % P19939 Apolipoprotein C-I % Q6IFU8 Keratin, type I cytoskeletal % P85411 Keratinocyte differentiationassociated protein % P04638 Apolipoprotein A-II %