Biochemical controls: cell metabolisms control developments (Introduction)

by David Turell , Friday, March 21, 2025, 18:40 (13 days ago) @ David Turell

It is not just gene information:

https://www.quantamagazine.org/how-metabolism-can-shape-cells-destinies-20250321/

“'Instead of thinking about the gene expression networks just happening to interact with metabolism, it’s really metabolism driving [developmental decision-making],” he said, “and gene expression networks are the tools by which that occurs.”

"This idea — that cell metabolism is an integral but unheralded part of the developmental process — isn’t fantastical. In another field of biology, epigenetics, researchers have already detailed the process by which metabolites turn genes on and off. But they needed the work of developmental biologists to connect more of the dots.

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"Epigeneticists who study this process have, over the past few decades, elucidated a complex system by which proteins and enzymes activate or repress certain genes. The meters-long strand of DNA in every cell is wound around proteins called histones. With the help of specific enzymes, molecules that scientists call “chemical modifications” or “epigenetic marks” attach to the histones and cause the DNA to unspool, exposing different genes for activation. These modifications can thereby activate some genes and deactivate others, influencing the biochemical processes in a cell and therefore the functions that cell performs.

“'Those chemical modifications that decorate [histones] and modify gene expression — they’re metabolites, full stop,” said Finley, the cancer biologist. “Chemical modifications themselves are metabolites, and their removal is dependent on metabolites.”

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"The nucleus’s metabolic activity was specific to the functions in that compartment, including epigenetic activity. “There are a lot of metabolic enzymes that are actually in the nucleus and are dynamically regulated in the nucleus,” said Wellen, who now heads a lab at the University of Pennsylvania. “We were really excited to find that.”

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“'What is intriguing is that all of this is associated with a massive accumulation of metabolic enzymes in the nucleus,” said Żylicz, the developmental biologist. These enzymes make molecules, which then activate other enzymes that remove epigenetic marks and lay down new ones as cells grow, divide and take on different fates.

"During this period, the cell moves many enzymes(opens a new tab) from the cytoplasm and mitochondria to the nucleus. That way, the metabolites necessary for gene activity can be produced locally, in the nucleus, where they are needed, Żylicz said. “The moment where you reprogram the epigenome — that happens to be the same time when you’re also really using this nucleus as a metabolic compartment.”

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“'This is particularly exciting because if changing metabolism can change cell fate in a meaningful way, there is the possibility that you might be able to manipulate that therapeutically, where aberrant decisions of differentiation are causal for the disease — like in many forms of cancer,” said Rutter, who was not involved in the study.

"In some ways, this interplay between metabolism and genes is obvious: We know that life is influenced by both its genes and its environment. This new, exciting field of research shows at a molecular level how the materials available to our cells influence their fates, and ours."

Comment: so, it is not just genes ordering everything around. There is an active interplay and feedback from metabolic enzymes directing the cells toward goals. This cannot happen by chance.