Rethinking the Regulation of Cellular Metabolism

Abstract

Most biologists working today have not considered the problem of how signal transduction events, which commit cells to energetically demanding processes such as growth and division, are connected to cellular metabolism. The primary reason for this is that we have believed for the last 30 or more years that the metabolism of cells is a homeostatic, self-regulating process that does not depend on any extracellular input. The traditional view is that a mammalian cell decides to take up nutrients whenever its bioenergetic and synthetic reserves are depleted. However, a considerable body of evidence now exists that challenges the notion that the nutrient uptake and metabolism of metazoan cells are cell-autonomous.

Restricting Glutamine or Glutamine-Dependent Purine and Pyrimidine Syntheses Promotes Human T Cells with High FOXP3 Expression and Regulatory Properties

“…These Gln functions may be replaced by glutamate or a-ketoglutarate (17,18). In a recently published study using murine T cell cultures, a proportional increase in Foxp3 + T cells through Gln deprivation was reversed by a-ketoglutarate supplements (29).…”

“…2). Gln, upon conversion to a-ketoglutarate via glutamate, is a key substrate to replenish TCA cycle metabolites and support NADPH generation for macromolecular synthesis during cell growth and proliferation (17,18). If these pathways contributed to FOXP3 hi cell enrichment through Gln restriction, then providing extra a-ketoglutarate or glutamate should at least partially compensate for Gln to reverse this effect.…”

Understanding the Epigenetic Syntax for the Genetic Alphabet in the Kidney

“…Although we do not fully understand the molecular mechanism of long-term environmental programming, we know that cells constantly adjust their metabolic state to nutrient availability. 26,27 In yeast, for example, nutrient availability is the key determinant of fate. Most chromatin-modifying enzymes require substrates or cofactors that are intermediates of cell metabolism; for example, acetyl and methyl groups are needed for histone tail acetylation and methylation.…”

Reasons for cancer metastasis: A holistic perspective

“…The predilection of cancer cells to engage in a high rate of glycolysis, even under conditions of adequate oxygen supply, is referred to as the Warburg effect and was first described by the famous German biochemist Otto Warburg in 1924 (38). Approximately 90 years after its discovery, the Warburg effect has again attracted significant attention in the field of cancer research (38).…”

“…Approximately 90 years after its discovery, the Warburg effect has again attracted significant attention in the field of cancer research (38). A number of researchers suggest that glycolysis renders cancer cells superior to their normal peers regarding proliferation (39).…”