Cellular Computations
28/03/12 12:29 Filed in: GenomeWeb Daily Scan
Submitted by S. Pelech - Kinexus on Mon, 09/10/2012 - 05:08.
At first glance, the argument of energy considerations strongly influencing biochemical processes in cells seems compelling and intuitive. However, life is remarkably inefficient at the molecular level. There is an abundance of energy available from the sun and interior of our planet, and life forms filling every crevice on the Earth's surface can serve as food for others. As a consequence, cellular metabolism is very forgiving in its consumption of adenosine triphosphate (ATP), which fuels most of the biochemical reactions in cells. Bacteria have evolved to become more energy efficient, but with multicellular eukaryotes the same pressures are much less intense. Improvements in the ability to predate other organisms more than compensate for deficiencies in biochemistry.
Most of the DNA in eukaryotic species is unnecessary baggage. For example, the fruit fly Drosophila melanogaster has 0.165 billion base pairs (bp) in its chromosomes, whereas the mountain grasshopper Podisma pedestris has 14 billion bp. With more than 85-times more consumption of ATP to make DNA in grasshoppers compared to fruit flies, the former does not appear to be particularly disadvantaged. Over 97% of the DNA in human chromosomes does not encode proteins or RNA. Similar examples can be provided for other types of energy requiring reactions such as protein phosphorylation, where the average eukaryotic protein features over 30 phosphosites, but only a small number are actually regulatory.
In view of the apparent latitude that cells possess with respect to their energy consumption, it is hard to envision that their "cellular computing", i.e. their cellular regulatory systems", are tightly constrained by typical fluctuations in their ATP levels. Under optimal conditions, cellular ATP levels in eukaryotes are in the 1 to 3 millimolar concentration range. However, the Km's of many metabolite and protein kinases that utilize ATP as a substrate are commonly well below a concentration of 100 micromolar.
The Mehta and Schwab arXiv paper is highly theoretical and is not based on any real data. Their arguments that, for example, sporulation is really driven by cellular computation limitations from a lack of energy, are not compelling. Cell signalling proteins are commonly expressed at levels that are a hundred- to a thousand-times lower than metabolic pathway enzymes and structural proteins. Consequently, maintenance of intact cell regulatory signalling networks constitutes only a tiny fraction of the cell's overall energy and material requirements. Those cells that can sporulate do so in the absence of nutrients, because a fully functional regulatory protein networks instructs them to preserve their long term viability for better days.
Link to the original blog post.
At first glance, the argument of energy considerations strongly influencing biochemical processes in cells seems compelling and intuitive. However, life is remarkably inefficient at the molecular level. There is an abundance of energy available from the sun and interior of our planet, and life forms filling every crevice on the Earth's surface can serve as food for others. As a consequence, cellular metabolism is very forgiving in its consumption of adenosine triphosphate (ATP), which fuels most of the biochemical reactions in cells. Bacteria have evolved to become more energy efficient, but with multicellular eukaryotes the same pressures are much less intense. Improvements in the ability to predate other organisms more than compensate for deficiencies in biochemistry.
Most of the DNA in eukaryotic species is unnecessary baggage. For example, the fruit fly Drosophila melanogaster has 0.165 billion base pairs (bp) in its chromosomes, whereas the mountain grasshopper Podisma pedestris has 14 billion bp. With more than 85-times more consumption of ATP to make DNA in grasshoppers compared to fruit flies, the former does not appear to be particularly disadvantaged. Over 97% of the DNA in human chromosomes does not encode proteins or RNA. Similar examples can be provided for other types of energy requiring reactions such as protein phosphorylation, where the average eukaryotic protein features over 30 phosphosites, but only a small number are actually regulatory.
In view of the apparent latitude that cells possess with respect to their energy consumption, it is hard to envision that their "cellular computing", i.e. their cellular regulatory systems", are tightly constrained by typical fluctuations in their ATP levels. Under optimal conditions, cellular ATP levels in eukaryotes are in the 1 to 3 millimolar concentration range. However, the Km's of many metabolite and protein kinases that utilize ATP as a substrate are commonly well below a concentration of 100 micromolar.
The Mehta and Schwab arXiv paper is highly theoretical and is not based on any real data. Their arguments that, for example, sporulation is really driven by cellular computation limitations from a lack of energy, are not compelling. Cell signalling proteins are commonly expressed at levels that are a hundred- to a thousand-times lower than metabolic pathway enzymes and structural proteins. Consequently, maintenance of intact cell regulatory signalling networks constitutes only a tiny fraction of the cell's overall energy and material requirements. Those cells that can sporulate do so in the absence of nutrients, because a fully functional regulatory protein networks instructs them to preserve their long term viability for better days.
Link to the original blog post.