Transformer
by Nick Lane
🏆 Rated: 8/10
Summary
Detailed Notes
Introduction - Life Itself
What brings a city to life is the people, their movement from place to place, along with the flow of materials that sustains our daily existence.
We could map a city, see the structures. Cells are like cities. They also have structure to them. But the structures are not static, proteins moving, membranes forming, shifting.
Even the most powerful microscopes can't discriminate the moment-by-moment flow of energy and materials that animates all life, the unceasing changes that transform molecules over millionths of seconds, and distances of less than a millionth of a millimetre.
The difference between being alive or dead lies in energy flow, in the ability of cells to continually regenerate themselves from simpler building blocks.
It's not about genetics. Genetics is secondary to energetics.
Understanding the deep chemistry that animates life and fades as we die, illuminates some of the enduring mysteries of biology and our own existence.
Flux is the flow of changing chemicals. 3*10^18 nanoseconds of metabolism in a normal person
From the elephant to butyric acid bacterium - it is all the same. – Albert Kluyver
The pathways producing the simplest chemical building blocks are conserved through all of life. Proteins are built from 20 amino acids and the genetic instruction manual is the same, no matter in which cell you look.
Genes can express very differently in different environments. Same gene is far from same phenotype.
Information is obviously important, but it's only part of what makes us alive.
Proteins are molecular shape shifting machines. They can change their shapes thousands of times per second, but only to a few specific shapes. These shapes are named conformations. The DNA sequence only indirectly determines conformations.
Cells can shift and adapt flux by using multiple biochemical pathways with different protein machinery. This way they can still work, even if their environment changes and they don't get certain molecules anymore as input. They problem solve, up and down regulating genes to keep metabolic pathways chugging along.
It's hard to study metabolism because it changes moment to moment within cells, but cells also cooperate, exchanging chemicals. We're still a long way from understanding all these interacting changes over the course of a lifetime of any animal.
But despite all of that, metabolism is also constant, the outputs of it and the major possible pathways are the same. Cells as cities look alike.
A bacterial cell living deep down in the crust of the Earth makes its letters for DNA through the same succession of steps that you do, even if many of its genes have diverged almost beyond recognition.
Genes are far more malleable than metabolism.
Metabolism has been going on, unbroken on Earth, since 4 billion years, this version of a slow simmering fire, converting energy and materials into different shapes, is what life is. There's something deeply beautiful, almost spiritual about this idea.
Catalysts are not magic—they simply speed up reactions that happen spontaneously.
What is more meaningful than the chemistry that brings life alive?
Chapter 1 - Discovering the Nanocosm
Respiration and combustion are exactly equivalent processes.
If the two are the same process why don't we go up in flames? It turns out that our metabolism is like a really slow burning controlled flame. Not a runaway chain reaction.
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Carbon chains are at the heart of the Krebs cycle. Sugar is a C6 Carbon, and can be broken down into two Pyruvates - C3 carbon chains.
Succinate a C4 sugar increases metabolic rates by up to 600% in muscles, yet it doesn't get consumed. It acts as a catalyst which is weird for such a simple molecule. It gets weirder if you consider that it by itself should be fairly unreactive.
The Krebs cycle is about removing 2 Hydrogen from carboxylic acids.
Biochemical cycles are necessarily catalytic.
The Krebs cycle also known as citric acid cycle is taking in pyruvateconverting it into citrate and burning it down with oxygen to release energy and turning it to ocaloacetate which can react with another pyruvate to form citrate again to start the cycle anew.
Weirdly, pyruvate + ocaloacetate have a total of 7 carbons but citrate only has 6 so there needs to be one lost in the reaction somehow taken up somewhere else. This turns out to be the case and the missing chemical is acetyl coenzyme A - acetyl CoA. Lipmann discovered this.
Even though they understood that all of this was happening to take 2H from the carboxylic acids to burn them and conserve the energy in the form of ATP nobody knew how this happened exactly.
NAD shuttles H+ ions across the mitochondrial membrane and transfers electrons through the respiratory chain, ultimately combining the H+ ions and electrons with oxygen to form water. In the process the H+ ions streaming back across the membrane spin ATP Synthase which combines ADP and a phosphate by mechanical force. The mitochondrial membrane potential due to the proton gradient is the strength of the electrical field of a lightning volt. And if one were to unfold the mitochondrial membrane they would cover the area of four football fields. All charged with the power of a lightning bolt but somehow safely contained within our bodies.
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