Fig. 1.

Metabolism in totipotent stem cells. (A) Glycolysis is impaired due to the low activities of the rate-limiting enzymes hexokinase (HK) and phosphofructokinase 1 (PFK1). Totipotent stem cells use pyruvate as their major energy and carbon source instead, via pyruvate dehydrogenase (PDH) to generate acetyl-CoA (Ac-CoA) and via pyruvate carboxylase (PC) to generate oxaloacetate (OAA) for anaplerosis or gluconeogenesis. (B) ATP synthesis is dependent on mitochondrial oxidative phosphorylation driven by the electron transport chain (ETC) and ATP synthase. However, as mitochondrial replication has not yet initiated, the halving of mitochondrial mass with each round of mitosis leads to a drop in ATP levels during embryo cleavage. (C) Simultaneously, each mitochondrion matures and the inner mitochondrial membrane potential (ΔΨ_m) increases steadily, thus turning the exponential drop in ATP into a linear drop. (D) Bicarbonate (HCO₃⁻) is needed to buffer the pH and also provides a carbon source to OAA in the Krebs cycle for anaplerosis via PC or to nucleotide synthesis for DNA and RNA via carbamoyl phosphate synthetase (CAD). F6P, fructose-6-phosphate; FBP, fructose-1,6-bisphosphate; G6P, glucose-6-phosphate; LDHA, lactate dehydrogenase A; PPP, pentose phosphate pathway.