To grasp the Krebs cycle is to fathom the deep coherence of biology. It connects the first photosynthetic bacteria with our own 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. 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. Lane explains cellular processes for producing energy particularly cellular respiration in animals. He recounts the history of key discoveries that underlie our understanding of cellular respiration and profiles the scientists involved. He compares cellular respiration with photosynthesis in plants and variants of these processes in microbes, pointing out the similarities and differences. He shows how early forms of the same processes could have initiated life detailing a specific scenario in hydrothermal vents. Lane explores how cellular respiration impacts health and aging. He makes the case that increasing dysfunction in cellular respiration is a primary factor in the increased rate of cancer and Alzheimer’s as we age and in aging itself. 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. The Shuram conundrum revolves around the evidence that most of the carbon on earth was bound up by sulfate, as shown by the carbon isotope balance in the Shuram formation in Oman. The survivors on the end-Permian extinction were those that had evolved to make use of oxygen and clear out excess CO2 and sulfide. Lane posits that it was at this time that the Kreb's cycle evolved.

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. The great immunologist Peter Medawar said we age because we outlive our allotted time as determined by the statistical laws of selection. This textbook view sees ageing and the diseases of old age as little more than the unmasking of late-acting genes, whose effects do us in. Ageing is not driven by mutations in genes accumulating over time, but by changes in gene activity – epigenetics. 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? 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.While mutations may cause cancer, particularly in young people, most mutations found in people with cancer arise once the process is underway. The major problem is the decline in respiration efficiency with age; damage may be “caused by protein unfolding or cross-linking, oxidation by ROS or glycation (the tendency of sugars such as glucose to react with proteins and lipids).” ROS stands for reactive oxygen species, free radicals. The ROS signals the cell to slow down respiration to control the ROS. The Krebs cycle intermediate succinate accumulates causing epigenetic changes (so gene activity follows faulty metabolism rather than causing it) and the Krebs cycle sometimes flows in reverse, creating biosynthesis (this was the original direction of the Krebs cycle). The cellular environment now “shouts grow”. 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. Yet Transformer is being marketed to laypeople, so it’s appropriate to get a non-chemist’s take. Well, here it is. Because of the author’s obvious enthusiasm, the writing is never dry, despite all the long words and formulas. For me, reading it was like listening to a friend excitedly unspool a story you can’t really follow. You endure it because the emotion is gripping and you can tell she really needs to share. In fact, at one point, Lane breathlessly announces a certain experiment “was so beautiful I have to tell you about it.”

One of the most creative of today's biologists ... this is a book filled with big ideas, many of which are bold instances of lateral thinking. The Krebs cycle is a series of chemical reactions that take place (in part or entirely) in most living organisms. Running in one direction it explains respiration, the process by which organic molecules undergo controlled combustion to produce energy, while in reverse it is one of the ways that complex organic molecules can be constructed. At the same time we see the importance of flows of energy and electrical potentials in understanding life. It's heady stuff. Lane goes on to show how the same processes that support life can produce cancers - and why these processes change over time, resulting in ageing and death. Perfect for a trivia night or a long trip, #TrainTeasers will both test your knowledge of this country`s rail system and enlighten you on the most colourful aspects of its long history. Meet trunk murderers, trainspotters, haters of railways, railway writers, Ministers for Transport good and bad, railway cats, dogs and a railway penguin. This is NOT a book for number-crunching nerds. Many of the answers are guessable by the intelligent reader. It is a quiz, yes, but also a cavalcade of historical incident and colour relating to a system that was the making of modern Britain.

About the book

A thrilling tour of the remarkable stories behind the discoveries of some of life’s key metabolic pathways and mechanisms. He lays bare the human side of science… The book brings to life the chemistry that brings us to life. Joseph Moran, Science

In a footnote, the author confides that “probably only a tenth of what I wanted to write about actually made it into the book.” On behalf of humanities majors everywhere, I can only say thank goodness. 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. The third peculiarity is the genetic code itself. There are clues that hint at direct interactions between the letters in DNA and the amino acids of proteins. This means the code is not random. A random piece of RNA will template a small protein, giving it a sequence that is specified by those non-random interactions. If that speeds up metabolism—the Krebs cycle for example—then the random sequence will be selected. And that means there’s no problem with the origin of information in biology. 3. The first animals evolved through a high-wire metabolic balancing act. Lane is British and makes no concessions to American English. Experiments work “first go,” not first try. We fly in aeroplanes and put on jumpers instead of sweaters. And in the fall, perhaps we engage in a programme of maths or simply enjoy the tonne of colours in the trees. National Library of Medicine (NLM), were first published in 1979. The Vancouver Group expanded and evolved into theFor anyone, who has "suffered" through memorizing the Krebs/citric acid cycle as presented in biochemistry, this is the rest of the story. For the conventional dogma is so narrow and incomplete that in maybe only a few exceptional courses, does one get an idea of just how much more there is and how that fits in with the whole picture of metabolism. The reverse Krebs cycle was more widespread on the early Earth before the rise of oxygen. Photosynthesis evolved in the cyanobacteria long after ancient bacteria were converting CO2 and H2 into organic molecules to drive growth.

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. 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 The greatest risk factor for cancer is older age: cancer incidence increases exponentially with age. One might think this is explained by the steady accumulation of mutations with age. But the buildup of mutations with age seems to be too slow to explain either cancer or ageing as a process. Nor can it explain why humans do not have a higher cancer rate than, mice, despite having ten times as many rounds of DNA copying to make an individual. Also interesting was that many of our diseases, like cancer, are caused more by respiration problems than genetic problems.

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