PubMed · 7003345
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B Hess, A Boiteux, E M Chance. 1980. Dynamic compartmentation.. https://doi.org/10.1007/978-3-642-81503-4_12
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Metabolic pathways can influence cell fate decisions, yet their regulative role during embryonic development remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in regulating signaling pathways involved in mesoderm and endoderm specification. Using a mouse embryonic stem cell (mESC)-based in vitro model for gastrulation, we found that glycolysis inhibition increases ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. We further show that glycolysis acts as an upstream regulator of Nodal and Wnt signaling and that its influence on cell fate specification can be decoupled from its effects on growth. Finally, we confirm the generality of our findings using a human gastrulation model. Our work underscores the dependence of signaling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision-making.
Glycolysis stops where gluconeogenesis starts-at pyruvate, the central metabolite of biosynthesis. The early history of carbon metabolism is preserved in archaeal and bacterial enzymes for glucose synthesis and breakdown. Here, we summarize the distribution and phylogeny of enzymes involved in glycolysis, gluconeogenesis, and glycogen metabolism from genomes of cultured prokaryotes. The presence of glycolytic pathways in H2-dependent chemolithoautotrophs, including methanogens, which cannot grow on exogenous glucose, correlates with their use of glycogen for intracellular carbon storage. Glycogen synthesis and gluconeogenesis are universal among prokaryotes, but glycolysis is not, indicating that the enzymatic conversions of glycolysis arose in the gluconeogenic direction encompassing three phases: (1) an autotrophic origin from H2 and CO2 to pyruvate and triosephosphate (trunk glycolysis) fulfilling basic amino acid and cofactor synthesis in the last universal common ancestor, (2) from triosephosphate to glucose supplying cell wall (murein and pseudomurein) and nucleic acid biosynthetic requirements in the first free-living autotrophs, also giving rise to intracellular carbon reserves (glycogen), followed by (3) diversification and transfer of enzymes for glycogen-mobilizing glycolytic routes. An autotrophic origin of trunk glycolysis followed by glycogen-dependent origin of glucose utilization account for conservation, distribution, and diversity of enzymes observed in microbial sugar phosphate pathways.
End-stage renal disease is characterized by enhanced susceptibility for infectious diseases, carrying an important risk of morbidity and mortality. In the host's defense against bacterial infection, a central role is played by phagocytic ingestion of bacteria, followed by their destruction after metabolic production of oxygen free radical species. Our studies have concentrated on the energy delivery by the hexose monophosphate shunt (HMS) to NAD(P)H-oxidase, the enzyme responsible for free radical production. This evaluation was realized by measuring, in whole blood, the CO2 produced from standard quantities of radiolabeled glucose, with data normalized for the number of polymorphs in each sample. Our studies indicate that: (1) glycolysis is disturbed in uremic outpatients from a SCrea of 6 mg/dl and a CCr of 15 ml/min; (2) similar functional disturbances are found in pre-dialysis blood samples of hemodialyzed patients; (3) this functional disturbance is further intensified during dialysis with cuprophan, which is not the case for non-complement activating dialyzers; (4) the response is especially suppressed towards Staphylococcus Aureus, the bacterial species responsible for the majority of infections in uremia; (5) that functional disturbances are mainly related to uremic toxicity, dialyzer membrane bio(in)compatibility, and uremic anemia. Biochemical disturbances in PMNL, induced by a multifactorial patho-physiologic process, may therefore be related to the enhanced incidence of infection in uremic patients.