(A) Scheme of selected biochemical reactions and metabolites involved in acetyl-CoA metabolic flux. Acetyl-CoA can be generated from (1) fatty acid oxidation, (2) pyruvate oxidation, (3) amino acids catabolism, and (4) ethanol-derived acetate. Acetyl-CoA can be consumed for energy production via (5) tricarboxylic acid (TCA) cycle, (6) fatty acid biosynthesis, (7) cholesterol and steroid biosynthesis, and (8) acetylation process. Solid or dashed lines with arrow indicate single or multiple biochemical reactions, respectively. Hepatic concentrations of (B) acetyl-CoA, (C) short-chain acylcarnitines, (D) N-acetyl amino acids, and (E) thiamine and 2-hydroxyglutarate. Results are expressed in mole per gram (g) liver weight. Data are presented as floating bars (min to max, line at mean; N = 4/group) showing individual data points from wild-type (WT, closed circles) and Gclm-KO (KO, open circles) mice. *P < 0.05, **P < 0.01, ***P < 0.001 by two-way ANOVA with post-hoc Holm-Sidak's multiple comparisons test. (F) Relative mRNA abundance measured by Q-PCR. Results are expressed as mean ± S.D. (N = 4/group). *Compared to WT-CON, ^compared to WT-EtOH, or #compared to KO-CON: P < 0.05 by two-way ANOVA with post-hoc Holm-Sidak's multiple comparisons test. WT-CON, wild-type mice fed control diet; KO-CON, Glcm KO mice fed control diet; WT-EtOH, wild-type mice fed ethanol-containing diet; KO-EtOH, Glcm KO mice fed ethanol-containing diet; Glu, glutamate; TG, triglycerides; Thr, threonine; ACC, acetyl-CoA carboxylase; ACOX, acyl-CoA oxidase; ACSL, long-chain acyl-CoA synthetase; CYP17A1, cytochrome P450 17a1; DLD, dihydrolipoamide dehydrogenase; EBP, emopamil binding protein; IDH, isocitrate dehydrogenase; LPL, lipoprotein lipase; OGDC, oxoglutarate dehydrogenase complex; PCCA, propionyl-CoA carboxylase; PDC, pyruvate dehydrogenase complex; PDHA1, pyruvate dehydrogenase α1 subunit; SLC22A5, solute carrier family 22 member 5; SLC25A17, solute carrier family 25 member 17.