Transformer: The Deep Chemistry of Life and Death

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Energy from the sun is captured by plants (photosynthesis) and bottled up in molecules (otherwise known as food that is made of carbon, hydrogen, and oxygen, chemically speaking) which we humans then eat. The human Krebs cycle (electron transport chain) then strips out the energy (electrons) from this food and passes it on for cellular respiration. Think of it as taking a food molecule, ripping out the carbon and oxygen to make CO 2 waste, and then ripping out the hydrogen to make H 2O. This is basically taking hydrogen and burning it in oxygen to give us energy to crawl, walk, or run. Dr Lane describes it as “feeding hydrogen to the ravaging beast called oxygen.” One can think of the entirety of medicine as tending to faulty human cellular respiration. Dr Lane coherently shows how this small sliver of reality is embedded in a much more general evolutionary history, starting with alkaline vents at the bottom of the ocean and ending up at human consciousness. In between, the author plainly tells the tale of the development of DNA, the fluke of photosynthesis, oxygen in the atmosphere, the one-in-a-gabillion appearance of the eukaryotic cell, multicellular organisms, and animal predation, all grounded in survival of the fittest and death/extinction of the weakest. Despite my praise of parts of the book, I found it a slow-going read, especially when the author detailed the Kreb’s and other cycles. I am the first one to admit that it is difficult to take a complex subject such as biochemistry and explain it in a text-heavy scholarly medium like a book. Despite the illustrations, which I don’t find all that compelling, it was still difficult to follow, and I had the advantage of already understanding how it all worked. As we get older, our respiratory performance declines slowly. The rate of respiration is depressed the most at complex I, the largest and most complex of the respiratory complexes. Complex I is the main source of reactive oxygen species (ROS) from mitochondria, and the rate at which these escape (ROS flux) tends to creep up with age. Also, complex 1 is the only entry point for NADH. So the decline in complex I activity with age means that it’s no longer so easy to oxidise NADH.

Plants make use of rubisco for photosynthesis. Rubisco is inefficient and is as likely to fix CO2 as O2. CO2 levels were high when the molecule evolved, but even today the buildup of CO2 within the leaf causes crops to lose as much as one quarter of their yield. Amazingly, rubisco now turns out to be widespread in ancient bacteria, doing a totally different job: degrading sugars derived from the RNA of other cells, to support growth fueled by eating other cells. Over time damage occurs to molecular machinery such as proteins. Repairing or replacing them is one of the most energy-sapping tasks that cells face. Eventually the respiratory machinery itself is damaged, and ROS flux creeps up. Cells do what they must and compensate by suppressing respiration a little. NADH is oxidized less effectively and the Krebs cycle loses forward momentum. Intermediates such as succinate start to accumulate and seep out from the mitochondria. They activate proteins such as HIF1α, which in turn alter the behavior of thousands of genes, pushing cells into a senescent state or to their demise.Perhaps the only real critique I can make of the book regards the bit at the end about consciousness. Lane’s presentation of the hard problem of consciousness, as well as his argument for electric fields as a causative agent of consciousness, warranted more of a footnote than an epilogue. His arguments here weren’t particularly strong, and I almost think he’d be the first to admit this. Most bacteria and archaea don't use a closed Kreb's cycle; rather they use a forked pathway that allows them to adapt to oxygen availability. Lane suggests that the Ediacaran fauna (500 million years before the Cambrian) had little tissue differentiation and were unable to adapt to changing environmental conditions. In contrast, the bilateral ancestors of the Cambrian fauna had a variety of tissues that could work together to seek metabolic balance. By the dawn of the Cambrian, they were able to deal with oxygen and "Rising oxygen just gave them a turbocharge." It’s not possible to construct a plausible story by starting with a computer chip. Energy drives everything and life began at an energy gradient. National Library of Medicine (NLM), were first published in 1979. The Vancouver Group expanded and evolved into the The Krebs cycle is more of a roundabout than a complete cycle. The traffic flow of metabolism has to be controlled to do particular jobs. The single-celled organisms that came before animals could mostly do one thing at a time, so they needed to adjust their traffic flow. But animals have multiple tissues and can balance traffic flow through the Krebs cycle in one tissue differently than in another tissue. It’s a kind of symbiosis between mutually dependent tissues.

After reading this book, one will understand how this cycle of matter (eponymously named in the 1930s after Sir Hans Adolf Krebs) is a sound explanation for the origin of life, lifespan, and the end of life. You will learn how the whole beautiful process can be understood in terms of physical chemistry, which is a unique sweet spot in the massive space of possible scientific explanations. It is a remarkable story. Cancer cells need NADPH for biosynthesis and growth, and it is as important to them as ATP. Cells must wire their metabolism to get the balance between ATP, NADPH and carbon skeletons right. Aerobic respiration produces too much ATP, which actually switches off the glycolytic breakdown of glucose. Cancer cells must not make too much ATP, as it slows down their growth. Cancer cells switch over to aerobic glycolysis precisely because it makes less ATP, favoring faster growth. In this compulsive readable book, Lane takes us on a riveting journey, ranging from the flow of energy to new ways of understanding cancer. Lane provides a luminous understanding of how scientists, including Lane himself, are rethinking energy and living organisms’ The Krebs cycle is a set of nine reactions arranged in a circular fashion, each generating intermediate organic chemicals. In respiration, the primary output is ATP, but some of the intermediates are drawn off as precursors for the synthesis of amino acids, fats, sugars and more.Life started out using the Krebs cycle to convert gases into living cells—the engine of biosynthesis. But modern animals use it for biosynthesis and to generate energy. They can’t spin the cycle in both directions at the same time, so how did they manage? What does Lane say is the best thing we can do to have long healthy lives? You’d never guess. Eat a modest quantity of healthy food and stay active. 🙂 But be aware, there’s a large element of chance in health. For more information on the ICMJE Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work Hugely ambitious and tremendously exciting ... Transformer shows how a molecular dance from the dawn of time still sculpts our lives today. I read with rapt attention’ A thrilling tour of the remarkable stories behind the discoveries of some of life’s key metabolic pathways and mechanisms. [Lane] lays bare the human side of science… The book brings to life the chemistry that brings us to life.