Keith N. Frayn - Human Metabolism

12 Chapter 12Figure 12.1 A sufferer from Type 1 diabetes mellitus in the early days of insulin therapy, ...Figure 12.2 Typical plasma glucose and insulin responses to a carbohydrate load in Type 2 d...Figure 12.1.1 Redrawn from Felber, J. -P., Acheson, K. J., & Tappy, L. (1993) From Obesity to...Figure 12.3 The metabolic pattern in untreated Type 1 diabetes. Pathways accelerated by ins...Figure 12.4 Twenty-four-hour profiles of plasma glucose concentration in non-diabetic subje...Figure 12.5 Twenty-four-hour profiles of plasma non-esterified fatty acid (NEFA) concentrat...Figure 12.6 Plasma insulin concentrations in non-diabetic subjects and people with Type 1 d...Figure 12.7 Non-enzymatic glycation of proteins. A sugar molecule in its straight-chain, al...Figure 12.8 The polyol pathway for production and further metabolism of sorbitol. The enzym...

1 Cover

2 Table of Contents

3 Preface

1 C1

2 iii

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391 E1

The first edition of Metabolic Regulation: A Human Perspective appeared in 1996. (It was pink.) When the second edition was published (in green) in 2003, it seemed that a revolution was taking place in metabolism. Tissues that we always thought were ‘doing metabolism’ turned out to be secreting hormones, adipose tissue and leptin being the prime example. By 2010, when the third (blue) edition was published, there were yet more changes in our understanding of metabolism and its regulation. The regulation of gene expression by nutrients (including, for instance, the carbohydrate-response element binding protein) was much better understood than previously. The techniques of genetic manipulation had also increased our understanding of metabolic pathways. In 1996, nobody could have guessed that a mouse without the adipose tissue enzyme hormone-sensitive lipase would be viable, let alone relatively normal: that finding led to the discovery of another enzyme of fat mobilisation, adipose triglyceride lipase. Similar studies made us revise our ideas about other ‘well-established’ enzymes such as phosphoenolpyruvate carboxykinase. Now, in 2018, we see more radical developments in the field. We always thought that hormones were hormones and metabolites were metabolites – now we know that the distinction is far from clear, with many compounds we regard as metabolites signalling through receptors as do ‘true hormones,’ thereby modulating metabolism. (We note in passing that the late Derek Williamson – colleague to both of us, and mentor to one [RDE], would not have been surprised: he had long predicted that the ketone bodies had a signalling role.)

We have always recognised that this textbook needed to be regarded as a complement to a more conventional biochemistry textbook, which would give details of pathways rather than just notes on their regulation. We have both taught metabolism to biochemistry and medical students in Oxford, and for this edition decided to combine our areas of expertise and to add material to the book that would enable it to be used more independently. Thus, in Chapter 1of this new edition, we have provided overviews of metabolic pathways that will then be described in more detail in subsequent chapters. A particular emphasis of the later chapters, as in previous editions, is the tissue-specificity of these metabolic pathways. We are aware that this textbook is used by medical and nursing students and that has prompted us to include more material relevant to metabolism in clinical situations such as cancer, sepsis, and trauma. We hope this material will be of interest to all students, including those of nutrition and sports science, as it illustrates how metabolism may be perturbed. The small revision to the title of the book reflects these changes.