Fig. 7.

Summary of proposed metabolic adaptations in intrauterine growth restriction (IUGR) skeletal muscle that conserve energy utilization and result in the release of ammoniagenic amino acids (AAs; alanine, glutamine, glycine) and uric acid. Metabolites, AA uptake rates, and gene expressions of enzymes (italics) in the IUGR (n = 10) fetal skeletal muscle or plasma that were higher (green), lower (red), or unchanged (black) when compared with control (CON; n = 8) fetuses. Black and gray-shaded arrows and font show proposed increases and decreases, respectively, in metabolic pathway flux. Based on these analyses, we propose that reduced oxidative metabolism (through glycolysis and the TCA cycle) and reduced availability of phosphate and adenosine result in increased entry of ADP into a salvage pathway for ATP generation. AMP and ammonia are then overly produced in IUGR muscle. AMP is further processed to uric acid via AMP deaminase, and excess ammonia is converted and released into the plasma in the forms of glutamine and glycine. Alanine, which is a gluconeogenic substrate and released into the circulation, is produced as a result of a series of transamination reactions that alleviate the load of pyruvate and glutamate. α-KG, α-ketoglutarate; ADA, adenosine deaminase; BCAA, branched-chain amino acid; BCKA, branched-chain α-ketoacids; GCS, γ-glutamylcysteine synthetase; GLS, glutaminase; GS, glutamine synthetase; Pi, orthophosphate; PPi, diphosphate.