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Transformer: The Deep Chemistry of Life and Death

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This is probably the best book on biology (and more specifically biochemistry) that I’ve ever read. Brian Clegg, Popular Science Books Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected After reading this really good book, one will appreciate the famous Harold Morowitz line that “matter cycles and energy flows.” I regret not having had this book during medical school. Transformer is well worth the read. 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. 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’

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. Oxygenic photosynthesis first arose in cyanobacteria or their predecessors, but exactly when remains uncertain. The first unequivocal evidence is the Great Oxidation Event (familiarly called the ‘GOE’) around 2.3 billion years ago, when the planet turned rusty red and froze. Mitochondrial DNA inherited from the mother. The idea of mother's curse is that as male and female metabolisms differ, some mitochondrial mutations could be neutral for the female but bad for the male. Genes in the nucleus can evolve to fix problems with mitochondrial DNA in males. Crosses between species can cause ‘hybrid breakdown’, attributed to incompatibilities between mitochondrial and nuclear genes.As we age, our respiration slowly begins to run down, and that affects the way that the Krebs cycle spins. Instead of burning hydrogen stripped out from the Krebs cycle, or using intermediates to build the molecules of life, the cycle slows down or goes into reverse. Our cells start to behave like those ancient bacteria, fixing CO 2, to make more of me. I slow down and put on weight. But the worst offenders are cancer cells, which switch Krebs cycle to a setting that maximizes growth. When I saw this book being offered up on NetGalley, I was particularly interested in the subject, having majored in Biology/Human Anatomy and Physiology in college. Besides, the Kreb’s Cycle (and my favorite organelle, the mighty mitochondria) is one of the most important processes in the human body, one that provides the energy that allows it to hum along. 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 Unlike most popular science books, this one is short on “wow factor”— information amazing enough to wake up the non-specialist nodding off amongst the molecules. But it does reveal that we’re each made of up “at least 30 trillion cells,” all of which go through “a billion metabolic reactions every second.” That means the cells of a man in his mid-50s like the book’s author have already gone through reactions numbering 10 to the 32nd power, “roughly a billion times the number of stars in the known universe.”

Reactive Oxygen Species (ROS) are such vital physiological signals that cells go out of their way to keep ROS flux within tight physiological limits. Redox tone – the balance of electron sources and sinks in a cell – is as critical to homeostasis (our normal chemical balance) as temperature or acidity. Any damage to the respiratory chain will tend to increase ROS flux. 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. 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. 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.Also interesting was that many of our diseases, like cancer, are caused more by respiration problems than genetic problems.

The ICMJE is small group of editors of general medical journals who first met informally in Vancouver, British Columbia, 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? The underlying problem in cancer is an environment that continuously and erroneously shouts ‘grow!’. This toxic environment can be induced by mutations, infections, low oxygen levels … or the decline in metabolism associated with ageing itself. 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. 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.

By Rachel Mesch

At the heart of life is an amazing, conflicted merry-go-round of reactions called the Krebs cycle. This might seem like stuffy textbook biochemistry from decades ago, but it holds the secret to what brings a planet to life and our own lives to an end. An exhilarating account of the biophysics of life, stretching from the first stirrings of living matter to the psychology of consciousness. I felt as if I was there, every step of the way’ 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." 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. If that’s as clear to your ears as a morning hello, have I got a book for you! Unfortunately, it’s not to me: The tour of the chem lab during my high-school orientation included an eyewash station to save your sight from an errant spray of acid and a furled blanket with which you could smother yourself in case you caught fire. I’ve given chemistry a wide berth ever since.

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