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. 2021 Oct 22;6(20):e142464. doi: 10.1172/jci.insight.142464

Figure 4. Bsg deficiency is compensated for by alternative circuits that provide utilization of glycogenic amino acids into the TCA cycle.

Figure 4

(A) Schematic illustrating use of the glycogenic amino acid pathway to compensate for impaired gluconeogenesis resulting from Bsg deficiency. Ala, alanine; NH3, ammonia; αKG, α-ketoglutaric acid; Glu, glutamate; Gln, glutamine. (B and C) Endogenous glucose production in hepatocytes isolated from Bsg–/– (B) and Bsg+/+ (C) animals when cells were cultured in the absence or presence of 250 μM β-chloro-l-alanine hydrochloride (an inhibitor of Ala transaminase), 10 mM l-glutamine, and 20 μM EGCG (an inhibitor of Glu dehydrogenase) for 4 hours. Gray columns and black circles, Bsg–/–; white columns and circles, Bsg+/+ (n = 6/genotype). Scatter plots display the data for individual mice. Statistical analyses were performed using a 1-way ANOVA with post hoc Tukey’s test for multiple comparisons. (D and E) Static metabolome analysis of amino acids in livers (D) and skeletal muscles (E) from fasted Bsg+/+ or Bsg–/– mice (n = 7–8/genotype). Levels of amino acids in Bsg–/– skeletal muscles are exhibited with respect to those of Bsg+/+ muscles. (F and G) Blood glucose levels and AUC scores in fasting Bsg+/+ and Bsg–/– mice during alanine (F) or glutamine (G) tolerance tests (n = 5–9/genotype). (H) Expression levels of transcripts encoding ureagenesis-related proteins, including CPS1 and argininosuccinate synthase (ASS). mRNA levels were normalized to those encoding the housekeeping protein β-actin (n = 7–8/genotype). (I) Serum ammonia values in fasting Bsg+/+ and Bsg–/– mice (n = 7/genotype). For all relevant panels, data are presented as means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, for the comparison of Bsg+/+ and Bsg–/– at the indicated time point (2-tailed unpaired Student’s t test).