Transformer: The Deep Chemistry of Life and Death

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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. 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.

The green sulfur bacterium Chlorobium thiosulfatophilum lives by photosynthesis in stinking, sulfurous waters such as hot springs. It reverses the Krebs cycle by using ferredoxin which has a biologically unparalleled ability to press electrons onto even the most unreactive molecules. However, ferredoxin reacts spontaneously with oxygen, becoming readily oxidized by even low levels of the gas. So in the presence of oxygen the reverse Krebs cycle usually grinds to a halt. Bacteria that use it today are normally restricted to environments with very low oxygen levels.Some interesting observations: the Cambrian explosion was when the Krebs cycle was first used primarily to generate energy not biosynthesis, taking advantage of the increased oxygen available. Rubisco in plants is considered inefficient as it does not adequately distinguish oxygen from carbon dioxide, but this may be necessary to prevent oxidative damage. People with type II diabetes have double the risk of Alzheimer’s, which is increasingly looking like a metabolic disease to Lane and others. Lane notes that "cancer is a disease of the genome is too close to dogma." Different mutations are found in different parts of many tumours, often with little if any overlap, implying that the mutations accumulated during the growth of the tumor, rather than triggering its inception. Moreover, the same oncogene mutations are often found in normal tissues surrounding a tumor,

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. H2 will push its electrons onto the catalyst in alkaline conditions, but CO2 will only accept them from the catalyst in acidic conditions. Virtually all cells pump H+ out, making the outside about three pH units more acidic than the inside. 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’ 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 reverse Krebs cycle requires an input of energy (ATP) to work, which in modern bacteria is normally obtained from photosynthesis. H2 will react with CO2, using iron–sulfide catalysts, but works best at pressures of around 100 bar, equivalent to an ocean depth of about 1 kilometre.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. 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. 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.

Lane is among the vanguard of researchers asking why the Krebs cycle, the “perfect circle” at the heart of metabolism, remains so elusive more than eighty years after its discovery. Transformeris Lane’s voyage, as a biochemist, to find the inner meaning of the Krebs cycle—and its reverse—why it is still spinning at the heart of life and death today. 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. 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

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Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected This is probably the best book on biology (and more specifically biochemistry) that I’ve ever read. Brian Clegg, Popular Science Books 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. 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.