Transformer: The Deep Chemistry of Life and Death

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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.

Most of us know the Krebs cycle as a cycle of biochemical reactions linked to energy generation in cells. In short, when we burn fuels like glucose in cell respiration, we first break them down into simpler molecules composed of carbon, hydrogen, and oxygen. These are the intermediates that make up the Krebs cycle. Then we strip out the carbon as CO 2, and we burn the hydrogen in oxygen. The energy released is used to power an electrical charge on the membranes deep within our cells. This charge is as intense as a bolt of lightning—if you shrink yourself down to the size of a molecule, you’d feel an electrical charge of 30 million volts per meter! Vancouver Group. Its requirements for manuscripts, including formats for bibliographic references developed by the U.S.On average, we have one SNP every thousand letters, meaning that there are four or five million letters that differ across the human genome. Only a modest proportion of these are likely to influence the risk of a particular disease From the renowned biochemist and author of The Vital Question, an illuminating inquiry into the Krebs cycle and the origins of life. 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. This is a dense book. I read two others by Lane that discuss cellular respiration and its variants. Both cover many of the same points and were challenging but far more accessible. In particular, reading The Vital Question before reading this one was very helpful to me. I recommend it highly for those of us who prefer following fewer chains of chemical reactions and more text aimed at the non-biochemist. My review of The Vital Question covers much of what is in this book, so I will just write some brief notes here. For more information on the ICMJE Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work

International Committee of Medical Journal Editors (ICMJE), which meets annually. The ICMJE created the pagination, the shorter form provides sufficient information to locate the reference. The NLM now lists all authors. I read several of previous Lane's books, namely Vital Question, Life Ascending and Oxygen. My thinking about origins of life was since dominantly shaped by his work, which filled a major gap for me in my worldview about abiogenesis.Metabolism is the sum total of reactions occurring in an organism at any one moment. Metabolism keeps us alive—it is what being alive is. In one of our own cells, there are more than a billion metabolic reactions every second. That’s about a hundred billion trillion reactions in the last second, or a billion times the number of stars in the known universe. These reactions don’t all work properly, and damage inevitably accumulates. 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. Transformer is a complex yet accessible, illuminating, and thrilling exploration of the vitality and elemental mysteries of our existence. Even though nonscientists won’t be able to judge whether Lane makes a convincing case, he is periodically quite clear on his goals. Early on, he posits the essential question as “genes first or metabolism first? The thrust of this book is that energy is primal — energy flow shapes genetic information.” Later, he restates the proposition with added whimsy:

What is a feeling—love or hunger or pain—in physical terms? There is no obvious reason why the release of neurotransmitters or the depolarization of neurons should feel like anything at all. What’s new is that the reactions that make up the Krebs cycle and onwards can occur spontaneously. The Krebs cycle is the engine of life, turning gases into living things. Genes emerged from this metabolic whirl. But now we’re faced with a strange situation: the Krebs cycle simultaneously creates and destroys, giving it a yin and yang that (I argue) still dictates how our genes work, including our risk of diseases. 2. Metabolism gives meaning to genetic information.

In anoxygenic photosynthesis, chlorophyll is used to strip electrons from H2S which are then passed onto ferredoxin directly. The waste product is not oxygen but sulfur. The huge advantage here is that the sun now powers the transfer of electrons, without the need for burning fuel to power pumping. The disadvantage is that these bacteria still derive all their electrons from geological sources such as volcanoes and hydrothermal vents.

Mitochondrial genes tend to evolve much ten to fifty times faster than nuclear genes, as they are copied far more than nuclear genes, and so they accumulate more mutations. A clean-up process in early life sieves out the most detrimental mutations. That’s why mitochondrial diseases directly affect only about 1 in 5,000 of us. To grasp the Krebs cycle is to fathom the deep coherence of biology. It connects the first photosynthetic bacteria with our peculiar cells. It links the emergence of consciousness with the inevitability of death. And it puts the subtle differences between individuals in the same grand story as the rise of the living world itself. of Medical Journal Editors (ICMJE) recommends the following citation style, which is the now nearly universally The author further explains that life is able to take two gases and turn them into solid matter. Carbon dioxide and hydrogen are quite happy existing as they are, not reacting with anything; however, life lowers the thermodynamic barriers to transforming them and the Krebs cycle is integral to this.

Reviews

Lane has come to believe that the structure of cells is less important than what goes on within them, an idea with both theoretical and practical implications. It challenges the accepted theory of life on Earth emerging from a “primordial soup” on the planet’s surface and instead shifts the genesis to undersea thermal vents. It replaces the buildup of genetic mutations as the cause of aging and cancer with the slowing of cellular activity. And it imagines consciousness as the humming electrical fields of cell membranes. Pores in hydrothermal vents provide a steady supply of H2 and CO2, in just the right conditions needed to promote their reaction to make carboxylic acids. These form through chemical mechanisms that resemble steps of the reverse Krebs cycle, implying that this chemistry really is the primordial basis for metabolism. An alternate version of ICMJE style is to additionally list the month an issue number, but since most journals use continuous If all this language sounds like Klingon, that is because this book is really far from an easy read, which can be said for all Lane's books I have seen. He is an excellent writer (albeit prone to digressions), but the topic is so disconnected from other popularized science that it requires a lot of new learning and understanding. It does not help that all claimed rules have many exceptions, leaving me with a fuzzy feeling that I got a glimpse of something great, but cannot dare to make my own conclusions (such as, should I give up my metformin while I follow a ketogenic diet and active lifestyle because it seems to follow from the book outlook applied to metformin-related published papers that metformin acts like a handbrake i.e. that it hinders my progress and increases cancer occurrence risk, while it could help sedentary carb-overloaded persons).