My student textbook referred to here is Frayn, K. N. & Evans, R. D. (2019). Human Metabolism: A Regulatory Perspective, 4th edn. Oxford: Wiley Blackwell.Google Scholar

On the history of studies in human metabolism: Kleiber, M. (1961). The Fire of Life: An Introduction to Animal Energetics. New York: Wiley; McKie, D. (1990). Antoine Lavoisier: Scientist, Economist, Social Reformer. New York: Da Capo Press; Noble, D. (2008). Claude Bernard, the first systems biologist, and the future of physiology. Exp Physiol 93: 16–26.Google Scholar

On Professor Sir Hans Krebs: Hans Krebs – Facts www.nobelprize.org/prizes/medicine/1953/krebs/facts/ (on this website, you can read more about Hans Krebs and his discoveries in metabolism); Krebs, H. A. (1967). The making of a scientist. Nature 215: 1441–1445. (Hans Krebs, perhaps the most widely known metabolic scientist, explains how his receipt of the Nobel Prize reflected fortunate chances during his earlier years); Whitehead, D. (2010). Oh to be in Oxford now that Krebs is there…! The Biochemist 32: 54–55. (David Whitehead reflects on a time of metabolic discoveries in Oxford – and featuring an often-reproduced photo of Hans Krebs astride a moped – perhaps the original Krebs cycle?)CrossRefGoogle ScholarPubMed

On human liver glycogen: Nilsson, L. H. & Hultman, E. (1973). Liver glycogen in man – the effect of total starvation or a carbohydrate-poor diet followed by carbohydrate refeeding. Scand J Clin Lab Invest 32: 325–330.Google Scholar

On more detailed background reading: Frayn, K. N. & Evans, R. D. (2019). Human Metabolism: A Regulatory Perspective, 4th edn. Oxford: Wiley Blackwell. (This student textbook gives far more detail than the present book, but might be of interest for those wanting to pursue the subject); Gurr, M., Harwood, J., Frayn, K., Murphy, D., & Michell, R. (2016). Lipids: Biochemistry, Biotechnology and Health, 6th edn. Oxford: Wiley Blackwell. (This is a more specialised text. Some of the material in this chapter is based on it); Salway, J. G. (2017). Metabolism at a Glance, 4th edn. Oxford: Wiley Blackwell. (A clearly illustrated pictorial guide to metabolic pathways, aimed at undergraduate students).Google Scholar

More on fats: Pond, C. M. (1998). The Fats of Life. Cambridge: Cambridge University Press. (A readable account of the role of fats in the diet and in the body.)Google Scholar

On proteins: Protein Data Bank is a compendium of data on many proteins, showing the three-dimensional structure of the molecules in many cases. Insulin is at https://pdb101.rcsb.org/motm/14.Google Scholar

Collins, J. M., Neville, M. J., Hoppa, M. B., & Frayn, K. N. (2010). De novo lipogenesis and stearoyl-CoA desaturase are coordinately regulated in the human adipocyte and protect against palmitate-induced cell injury. J Biol Chem 285: 6044–6052. (A research paper including an example of how molecules may be ‘channelled’ along a pathway.)Google Scholar

On metabolic pathway charts: Hadlington, S. (2007). Life’s Cartographer. Chemistry World: www.chemistryworld.com/features/lifes-cartographer/3004664.article. (The personal story of Donald Nicholson, the man behind the chart of all known metabolic pathways); Nicholson, D. (2006). A lifetime of metabolism. Cell Mol Life Sci 63: 1–5. (Donald Nicholson’s own story of how he created the first map of metabolic pathways.)Google Scholar

On the history of discovery of metabolic pathways: Fritz, I. B. (1961). Factors influencing the rates of long-chain fatty acid oxidation and synthesis in mammalian systems. Physiol Rev 41: 52–129 (an influential review for this author setting out to study lipid metabolism); Kresge, N., Simoni, R. D., & Hill, R. L. (2005). Fritz Lipmann and the discovery of coenzyme A. J Biol Chem 280: e18; Kresge, N., Simoni, R. D., & Hill, R. L. (2005). Otto Fritz Meyerhof and the elucidation of the glycolytic pathway. J Biol Chem 280: e3.Google Scholar

BBC Bitesize: Coordination and control – The nervous system. www.bbc.co.uk/bitesize/guides/zprxy4j/revision/1 (a simple guide to the human nervous system).Google Scholar

Bliss, M. (1983). The Discovery of Insulin. Edinburgh: Paul Harris. (A very readable account of the early days in the story of insulin.)Google Scholar

On modification of enzyme activity by phosphorylation (adding a phosphate group to one of the protein’s constituent amino acids): Cohen, P. (2009). Keep nibbling at the edges. J Biol Chem 284: 23891–23901 (Professor Sir Philip Cohen gives a personal account of the discovery of protein phosphorylation as a means of regulating enzyme activity); Cohen, P. (2021). Edmond Fischer (1920–2021). Nature 597: 328 (Philip Cohen’s obituary for Edmond Fischer, one of the discoverers of protein phosphorylation to change enzyme activity, along with Edwin Krebs (not related to Hans Krebs): Fischer and Krebs were jointly awarded the Nobel Prize in Physiology or Medicine for their work in 1992).Google Scholar

Protein Data Bank: https://pdb101.rcsb.org/motm/14 (this web page shows the structure of insulin (shown in Figure 2.6) and discusses insulin’s actions).Google Scholar

Robinson, A. M. & Williamson, D. H. (1980). Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev 60: 143–187.Google Scholar

Sriram, K. & Insel, P. A. (2018). G protein-coupled receptors as targets for approved drugs: how many targets and how many drugs? Mol Pharmacol 93: 251–258. (This review highlights just how important the G protein-coupled receptors are for medicine development.)Google Scholar

Stallknecht, B., Lorentsen, J., Enevoldsen, L. H., Bülow, J., Biering-Sørensen, F., Galbo, H., & Kjaer, M. (2001). Role of the sympathoadrenergic system in adipose tissue metabolism during exercise in humans. J Physiol 536: 283–294.CrossRefGoogle ScholarPubMed

On mitochondria – origins and function: Friedman, J. R. & Nunnari, J. (2014). Mitochondrial form and function. Nature 505: 335–343; Newman, T. What are mitochondria? Medical News Today. Available at: www.medicalnewstoday.com/articles/320875CrossRefGoogle ScholarPubMed

Guo, R., Gu, J., Zong, S., Wu, M. & Yang, M. (2018). Structure and mechanism of mitochondrial electron transport chain. Biomed J 41: 9–20. (In this open-access paper, Guo and colleagues describe what they term the ‘respirasome’, the complex of enzymes within the mitochondrion that brings about oxidation and ATP synthesis. It has clear pictures showing how the enzymes are arranged.)Google Scholar

Manzo-Avalos, S. & Saavedra-Molina, A. (2010). Cellular and mitochondrial effects of alcohol consumption. Int J Environ Res Public Health 7: 4281–4304. (An open-access paper giving more information about the metabolism of alcohol.)Google Scholar

Martinez-Reyes, I. & Chandel, N. S. (2020). Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 11: 102. (A more in-depth open-access paper with information on the citric acid cycle (here called tricarboxylic acid, TCA, cycle).)Google Scholar

Nobel Prize in Chemistry (1978). www.nobelprize.org/prizes/chemistry/1978/summary/ (an account of Peter Mitchell’s work on the chemiosmotic theory of ATP synthesis).Google Scholar

Fery, F. D., Attellis, N. P., & Balasse, E. O. (1990). Mechanisms of starvation diabetes: study with double tracer and indirect calorimetry. Am J Physiol 259: E770–E777. (A research paper, not open access unfortunately but the abstract will give an idea how isotopic tracers can be used to study dynamic changes in metabolism following a meal (in this case, a glucose drink).)Google ScholarPubMed

On glucose and lactate inter-relationships: Brooks, G. A. (2020). Lactate as a fulcrum of metabolism. Redox Biol 35: 101454; Rabinowitz, J. D. & Enerbäck, S. (2020). Lactate: the ugly duckling of energy metabolism. Nat Metab 2: 566–571.Google Scholar

Kiela, P. R. & Ghishan, F. K. (2016). Physiology of intestinal absorption and secretion. Best Pract Res Clin Gastroenterol 30: 145–159. (An open-access review of this topic with much emphasis on micronutrients (such as vitamins) but also covering glucose, fats, and amino acids.)Google Scholar

On liver glucose metabolism: Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017). Regulation of hepatic glucose metabolism in health and disease. Nat Rev Endocrinol 13: 572–587; Roach, P. J., Depaoli-Roach, A. A., Hurley, T. D. & Tagliabracci, V. S. (2012). Glycogen and its metabolism: some new developments and old themes. Biochem J 441: 763–787. (These are both open-access review papers giving detail about these systems in health and disease.)Google Scholar

On fat metabolism: Frayn, K. N., Arner, P. & Yki-Järvinen, H. (2006). Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem 42: 89–103.Google Scholar

Krebs, H. A. (1972). Some aspects of the regulation of fuel supply in omnivorous animals. Adv Enz Reg 10: 397–420. (Hans Krebs reflects especially on why amino acids are used as a metabolic fuel when present in excess.)CrossRefGoogle ScholarPubMed

Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. BMJ 361: k2179. (An accessible review on this topic.)Google Scholar

Yang, A. & Mottillo, E. P. (2020). Adipocyte lipolysis: from molecular mechanisms of regulation to disease and therapeutics. Biochem J 477: 985–1008 (open-access).CrossRefGoogle ScholarPubMed

Ashcroft, F. (2000). Life at the Extremes: The Science of Survival. London: Flamingo. (This readable book explores in more depth the adaptability of human physiology and metabolism.)Google Scholar

Benedict, F. G. (1915). A Study of Prolonged Fasting. Washington, DC: Carnegie Institute of Washington. Available via Forgotten Books: www.forgottenbooks.com/en/books/AStudyofProlongedFasting_10266160.Google Scholar

On the Minnesota experiment on semi-starvation: Kalm, L. M. & Semba, R. D. (2005). They starved so that others be better fed: remembering Ancel Keys and the Minnesota experiment. J Nutr 135: 1347–1352 (an account of Ancel Keys and the Minnesota Experiment on semi-starvation: not open-access but even the abstract will give you a feel for what was involved); Keys, A., Brožek, J., Henschel, A., Mickelsen, O., & Taylor, H. L. (1950). The Biology of Human Starvation, Volumes 1 & 2. Minneapolis, MN: University of Minnesota Press. https://doi.org/10.5749/j.ctv9b2tqv; Tucker, T. (2008). The Great Starvation Experiment: Ancel Keys and the Men Who Starved for Science. Minneapolis, MN: University of Minnesota Press.Google Scholar

Owen, O. E., Morgan, A. P., Kemp, H. G., Sullivan, J. M., Herrera, M. G. & Cahill, G. F. (1967). Brain metabolism during fasting. J Clin Invest 46: 1589–1595.Google Scholar

Owen, O. E. (2005). Ketone bodies as a fuel for the brain during starvation. Biochem Mol Biol Edu 33: 246–251. (Oliver Owen’s personal account of the classic studies on starvation of obese patients during the 1960s and later, under George Cahill.)Google Scholar

On different patterns of physical activity: Thompson, D., Karpe, F., Lafontan, M., & Frayn, K. (2012). Physical activity and exercise in the regulation of human adipose tissue physiology. Physiol Rev 92: 157–191; Thompson, D., Peacock, O., Western, M., & Batterham, A. M. (2015). Multidimensional physical activity: an opportunity, not a problem. Exerc Sport Sci Rev 43: 67–74.Google Scholar

Hawley, J. A., Maughan, R. J., & Hargreaves, M. (2015). Exercise metabolism: historical perspective. Cell Metab 22: 12–17. (An open-access review by three of the top scientists in exercise metabolism, giving a history of the field.)Google Scholar

On muscle metabolism in anaerobic exercise: Crowther, G. J., Carey, M. F., Kemper, W. F. & Conley, K. E. (2002). Control of glycolysis in contracting skeletal muscle. I. Turning it on. Am J Physiol Endocrinol Metab 282: E67–E73; Crowther, G. J., Kemper, W. F., Carey, M. F. & Conley, K. E. (2002). Control of glycolysis in contracting skeletal muscle. II. Turning it off. Am J Physiol Endocrinol Metab 282: E74–E79; Westerblad, H., Allen, D. G. & Lannergren, J. (2002). Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci 17: 17–21.Google Scholar

On muscle glycogen and exercise: Bergström, J. & Hultman, E. (1966). Muscle glycogen synthesis after exercise: an enhancing factor localized to the muscle cells in man. Nature 210: 309–310 (the original observation of ‘supercompensation’); Murray, B. & Rosenbloom, C. (2018). Fundamentals of glycogen metabolism for coaches and athletes. Nutr Rev 76: 243–259.Google Scholar

On fatty acids and stress: Frayn, K. N., Williams, C. M., & Arner, P. (1996). Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases? Clin Sci 90: 243–253 (summarises the data behind the speculations about stress and heart disease). Newsholme, E. A. & Leech, A. R. (1983). Biochemistry for the Medical Sciences. Chichester: John Wiley (in this textbook the late British biochemist Eric Newsholme and his colleague Tony Leech present a detailed view of metabolism including speculations about fatty acids and stress. Their more recent book Functional Biochemistry in Health and Disease (Wiley-Blackwell, 2009) brings the biochemistry up to date but lacks some of the anecdotes).Google Scholar

Ashcroft, F. (2000). Life at the Extremes: The Science of Survival. London: Flamingo. (This readable book explores in more depth the adaptability of human physiology and metabolism.)Google Scholar

Benedict, F. G. (1915). A Study of Prolonged Fasting. Washington, DC: Carnegie Institute of Washington. Available via Forgotten Books: www.forgottenbooks.com/en/books/AStudyofProlongedFasting_10266160.Google Scholar

On the Minnesota experiment on semi-starvation: Kalm, L. M. & Semba, R. D. (2005). They starved so that others be better fed: remembering Ancel Keys and the Minnesota experiment. J Nutr 135: 1347–1352 (an account of Ancel Keys and the Minnesota Experiment on semi-starvation: not open-access but even the abstract will give you a feel for what was involved); Keys, A., Brožek, J., Henschel, A., Mickelsen, O., & Taylor, H. L. (1950). The Biology of Human Starvation, Volumes 1 & 2. Minneapolis, MN: University of Minnesota Press. https://doi.org/10.5749/j.ctv9b2tqv; Tucker, T. (2008). The Great Starvation Experiment: Ancel Keys and the Men Who Starved for Science. Minneapolis, MN: University of Minnesota Press.Google Scholar

Owen, O. E., Morgan, A. P., Kemp, H. G., Sullivan, J. M., Herrera, M. G. & Cahill, G. F. (1967). Brain metabolism during fasting. J Clin Invest 46: 1589–1595.Google Scholar

Owen, O. E. (2005). Ketone bodies as a fuel for the brain during starvation. Biochem Mol Biol Edu 33: 246–251. (Oliver Owen’s personal account of the classic studies on starvation of obese patients during the 1960s and later, under George Cahill.)Google Scholar

On different patterns of physical activity: Thompson, D., Karpe, F., Lafontan, M., & Frayn, K. (2012). Physical activity and exercise in the regulation of human adipose tissue physiology. Physiol Rev 92: 157–191; Thompson, D., Peacock, O., Western, M., & Batterham, A. M. (2015). Multidimensional physical activity: an opportunity, not a problem. Exerc Sport Sci Rev 43: 67–74.Google Scholar

Hawley, J. A., Maughan, R. J., & Hargreaves, M. (2015). Exercise metabolism: historical perspective. Cell Metab 22: 12–17. (An open-access review by three of the top scientists in exercise metabolism, giving a history of the field.)Google Scholar

On muscle metabolism in anaerobic exercise: Crowther, G. J., Carey, M. F., Kemper, W. F. & Conley, K. E. (2002). Control of glycolysis in contracting skeletal muscle. I. Turning it on. Am J Physiol Endocrinol Metab 282: E67–E73; Crowther, G. J., Kemper, W. F., Carey, M. F. & Conley, K. E. (2002). Control of glycolysis in contracting skeletal muscle. II. Turning it off. Am J Physiol Endocrinol Metab 282: E74–E79; Westerblad, H., Allen, D. G. & Lannergren, J. (2002). Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci 17: 17–21.Google Scholar

On muscle glycogen and exercise: Bergström, J. & Hultman, E. (1966). Muscle glycogen synthesis after exercise: an enhancing factor localized to the muscle cells in man. Nature 210: 309–310 (the original observation of ‘supercompensation’); Murray, B. & Rosenbloom, C. (2018). Fundamentals of glycogen metabolism for coaches and athletes. Nutr Rev 76: 243–259.Google Scholar

On fatty acids and stress: Frayn, K. N., Williams, C. M., & Arner, P. (1996). Are increased plasma non-esterified fatty acid concentrations a risk marker for coronary heart disease and other chronic diseases? Clin Sci 90: 243–253 (summarises the data behind the speculations about stress and heart disease). Newsholme, E. A. & Leech, A. R. (1983). Biochemistry for the Medical Sciences. Chichester: John Wiley (in this textbook the late British biochemist Eric Newsholme and his colleague Tony Leech present a detailed view of metabolism including speculations about fatty acids and stress. Their more recent book Functional Biochemistry in Health and Disease (Wiley-Blackwell, 2009) brings the biochemistry up to date but lacks some of the anecdotes).Google Scholar

On how much we eat in 10 years: data taken from Public Health England/Food Standards Agency (2018). National Diet and Nutrition Survey Results from Years 7 and 8 (combined) of the Rolling Programme (2014/2015 to 2015/2016). London: Crown Copyright.Google Scholar

Whitley, H. A., Humphreys, S. M., Samra, J. S., Campbell, I. T., Maclaren, D. P. M., Reilly, T. & Frayn, K. N. (1997). Metabolic responses to isoenergetic meals containing different proportions of carbohydrate and fat. Br J Nutr 78: 15–26.Google Scholar

On the physiological role of de novo lipogenesis: Acheson, K. J., Flatt, J. P., & Jéquier, E. (1982). Glycogen synthesis versus lipogenesis after a 500 gram carbohydrate meal in man. Metabolism 31: 1234–1240; Acheson, K. J., Schutz, Y., Bessard, T., Anantharaman, K., Flatt, J.-P. & Jéquier, E. (1988). Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am J Clin Nutr 48: 240–247.Google Scholar

King, R. F. G. J., Almond, D. J., Oxby, C. B., Holmfield, J. H. M., & McMahon, M. J. (1984). Calculation of short-term changes in body fat from measurement of respiratory gas exchange. Metabolism 33: 826–832.Google Scholar

On metabolic interactions between carbohydrates and fat: McGarry, J. D., Mannaerts, G. P., & Foster, D. W. (1977). A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest 60: 265–270; McGarry, J. D. (1979). Lilly Lecture 1978. New perspectives in the regulation of ketogenesis. Diabetes 28: 517–523; Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963). The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1: 785–789.Google Scholar

On longer-term regulation of gene expression by nutrients: Ferré, P. & Foufelle, F. (2007). SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res 68: 72-82; González, A. & Hall, M. N. (2017). Nutrient sensing and TOR signaling in yeast and mammals. EMBO J 36: 397–408; Ortega-Prieto, P. & Postic, C. (2019). Carbohydrate sensing through the transcription factor ChREBP. Front Genet 10: 472.Google Scholar

On genetics: Kampourakis, K. (2020). Understanding Evolution. Cambridge: Cambridge University Press; Kampourakis, K. (2022). Understanding Genes. Cambridge: Cambridge University Press.Google Scholar

On Mendelian inheritance of metabolic diseases: Online Mendelian Inheritance in Man (OMIM) is a free, online database (© Johns Hopkins University), and such disorders are often referred to be their OMIM catalogue number. Scriver’s The Online Metabolic & Molecular Bases of Inherited Disease is a commercial catalogue.Google Scholar

On hereditability of leanness and obesity: Haworth, C. M., Plomin, R., Carnell, S., & Wardle, J. (2008). Childhood obesity: genetic and environmental overlap with normal-range BMI. Obesity (Silver Spring) 16: 1585–1590; Locke, A. E., Kahali, B., Berndt, S. I., et al. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature 518: 197–206.CrossRefGoogle ScholarPubMed

On diabetes history and treatment: Bliss, M. (1983). The Discovery of Insulin. Edinburgh: Paul Harris; Mathieu, C., Martens, P. J., & Vangoitsenhoven, R. (2021). One hundred years of insulin therapy. Nat Rev Endocrinol. https://doi.org/10.1038/s41574–021-00542-w; Taylor, R., Al-Mrabeh, A., & Sattar, N. (2019). Understanding the mechanisms of reversal of type 2 diabetes. Lancet Diabetes Endocrinol 7: 726–736;Google Scholar

On cardiovascular disease mortality: Dagenais, G. R., Leong, D. P., Rangarajan, S., et al. (2020). Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study. Lancet 395: 785–794; WHO data: www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).Google Scholar

On metabolism in cancer cells: Deberardinis, R. J. & Chandel, N. S. (2020). We need to talk about the Warburg effect. Nat Metab 2: 127–129; Swinnen, J. V., Brusselmans, K., & Verhoeven, G. (2006). Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care 9: 358–365.CrossRefGoogle ScholarPubMed