Metabolism in Cellular Proliferation and Growth.

Cellular proliferation with growth is an energy-intensive and substrate-demanding process. Food availability and growth factors work together to make this happen. Metabolism is at the center of this. Glycolysis and glutaminolysis are enhanced and storage as lactic acid and malic acid helps draw on lipolysis to supply the Krebs cycle for the tissue building intermediates and NADH, FADH2 and GTP; and much more ATP therefrom, in oxidative phosphorylation.

In cellular proliferative and growth states, glycolic metabolism provides steady supply of acetyl CoA, which now does not get to the mitochondria, already preoccupied with the formed acetyl CoA, from the mitochondrial beta oxidation of lipids, to form citrate and sustain the citrate cycle. The cycle then provides the metabolic building blocks and ATP for anabolism, as glycolysis is providing acetyl CoA, for lipogenesis and cholesterolgenesis, used in building the cell membrane and for the synthesis of growth steroids, as well as for histone acetylation and enhanced gene expression needed for growth and cellular differentiation.

In stress, however, gylocolysis is shut down because glucose provides fewer calories per weight than fat(4 and 9 kilocalories/gm respectively) and this allows more efficient and rapid mobilization of energy resources. Blood sugar levels spike, from glycolysis shutdown. However, since stress provokes enhanced beta oxidation[from adrenaline], a much rapid process, there is increased oxygen free radicals production, which is not desirable for a proliferating stem cell; but good for growth and cellular differentiation.

In the light of these needs for the stem cell proliferative state, the shutting down of glycolysis will be counterproductive, given the enormous metabolic demands necessary for both energy use and tissue synthesis and the need for a reduced environment in the stem cell proliferation. However, cell differentiation, if it has to follow, as in normal tissue, will call for enhanced beta oxidation that comes with free radical production to meet the demands imposed by histone acetylation and enhanced gene expression.

Excessive dietary citrate enhances oxygen uptake and may fight cancer; which cells do not differentiate appreciably, and may be forced to do so with the enhanced metabolism and growth forced onto it by the citrate.

Dr. Oliver Verbe Birnso, MD.

Comments

  1. ChloeMarch 14, 2016 at 10:23 PM

    In order to identify putative autocrine growth factors or targets for growth of cells, differentiation and proliferation may lead to new ways of forming beta.

    ReplyDelete

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