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Transformer: The Deep Chemistry of Life and Death

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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 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.

Until now, biology has tended to study the materials that make up the instruments. The time has come to close our eyes and listen to the music.” This is probably the best book on biology (and more specifically biochemistry) that I’ve ever read. Brian Clegg, Popular Science Books 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.The response to drugs can vary dramatically, depending on a few tiny differences in mitochondrial DNA, with big differences in outcome between males and females. 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. 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. 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 A warts-and-all portrait of the famed techno-entrepreneur—and the warts are nearly beyond counting.

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. 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.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”.

ageing, related diseases and cancer newly explained as consequences of slowing and reversing the Krebs cycle 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. I thought the best part of the book was how the author detailed the scientists’ quest to discover those elusive secrets. I also quite enjoyed the appendix and source material that he used. Rather than just a list of articles and books, the author took the time to review most of the research material in detail, giving the reader many starting points should they wish to further investigate the subject on their own.

By Rachel Mesch

Halpern SD, Ubel PA, Caplan AL, Marion DW, Palmer AM, Schiding JK, et al. Solid-organ transplantation in HIV-infected National Library of Medicine (NLM), were first published in 1979. The Vancouver Group expanded and evolved into the

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