Оглавление
Keith N. Frayn. Human Metabolism
Human Metabolism. A Regulatory Perspective
CONTENTS
List of Tables
List of Illustrations
Guide
Pages
Preface
Abbreviations
About the companion website
CHAPTER 1 The underlying principles of human metabolism. Key learning points
1.1 Metabolism in perspective
1.2 The chemistry of food – and of bodies
1.2.1 Some important chemical concepts. 1.2.1.1 Polarity
Box 1.1 Ionisation state of some acids at normal hydrogen ion concentrations
1.2.1.2 Osmosis
1.2.1.3 Reduction-oxidation
Box 1.2 Redox reactions
1.2.2 The chemical characteristics of macronutrients. 1.2.2.1 Carbohydrates
1.2.2.2 Fats
Box 1.3 The structures and interrelationships of fatty acids
1.2.2.3 Proteins
1.3 General overview of metabolism. 1.3.1 Human metabolic pathways
Box 1.4 Anabolism and catabolism
1.3.1.1 Energy transduction
1.3.1.2 Energy substrates
1.3.1.3 Metabolic strategy
1.3.1.4 Tricarboxylic acid (TCA) cycle
Box 1.5 Tricarboxylic acid cycle: overall scheme
1.3.1.5 Electron transport chain
Box 1.6 High-energy bonds
1.3.2 Carbohydrate metabolism. 1.3.2.1 Pathways of glucose metabolism
1.3.2.1.1 Glucose phosphorylation
1.3.2.1.2 Glycolysis
1.3.2.1.3 Lactate and ethanol metabolism
1.3.2.1.4 Pyruvate oxidation
1.3.2.1.5 Gluconeogenesis
1.3.2.1.6 Glycogen metabolism
1.3.2.1.7 Pentose phosphate pathway
1.3.3 Lipid metabolism. 1.3.3.1 Pathways of lipid metabolism
1.3.3.2 Fat deposition and mobilisation
1.3.3.3 Fatty acid oxidation
Box 1.7 Fatty acid oxidation
1.3.3.4 Fatty acid synthesis
1.3.4 Protein metabolism. 1.3.4.1 Pathways of amino acid metabolism
1.3.4.2 Amino acid-nitrogen disposal
Box 1.8 Deamination
1.3.4.3 Metabolism of the carbon skeleton
SUPPLEMENTARY RESOURCES
Note
CHAPTER 2 Cellular aspects of metabolic regulation. Key learning points
2.1 What is metabolic regulation?
2.2 What makes one tissue different from another? 2.2.1 Tissue-specific enzyme expression
2.2.2 Movement of substances across membranes
Box 2.1 Movement of molecules across membranes
2.2.2.1 Glucose transport
Box 2.2 Transport of glucose across cell membranes
Box 2.3 Classification of solute transporters
2.2.2.2 Amino acids
2.2.2.3 Fatty acids
2.2.2.4 Cholesterol
2.2.2.5 Small polar molecules
2.2.2.6 Water and glycerol
2.3 Rapid changes in metabolic flux and how they are achieved. 2.3.1 Rapid and longer-term changes in metabolic flux
Box 2.4 Protein conformation and metabolic regulation
Allostery
Covalent modification, especially reversible phosphorylation
Other forms of covalent modification of proteins
Box 2.5 Role of NAD in metabolic regulation
2.3.2 Regulation of substrate delivery through the bloodstream
2.3.3 Substrate cycling
2.4 Longer-term control of metabolic pathways
2.4.1 Innate changes in metabolism with time
2.4.2 Nutrients and control of gene expression
2.4.2.1 Carbohydrate responsive genes
2.4.2.2 Fatty acids and gene expression
2.4.2.3 Cholesterol and gene expression
2.4.2.4 Amino acids and gene expression
2.4.2.5 Regulation of oxidative metabolism by gene expression
SUPPLEMENTARY RESOURCES
Note
CHAPTER 3 Coordination of metabolism in the whole body. Key learning points
3.1 Metabolic regulation involves communication between tissues
3.2 What connects the tissues?
3.2.1 Circulation, capillaries, interstitial fluid
3.2.2 Blood, blood plasma and serum
3.2.3 Lymph and lymphatics
3.3 Hormones and their receptors
Box 3.1 The difference between a metabolite and a hormone
3.4 Hormones and short-term control of enzyme activity
Box 3.2 G protein-coupled receptors (GPCRs)
Box 3.3 Components of signal transduction chains. Receptors
G-proteins
Small molecules
Enzymes
Protein kinases
Protein phosphatases
Box 3.4 Signal transduction chains: some examples
3.5 Hormones and longer-term control of enzyme activity
3.5.1 Insulin and control of gene expression
3.5.2 Steroid and thyroid hormones
Box 3.5 Nuclear receptors
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CHAPTER 4 Digestion and intestinal absorption. Key learning points
4.1 The strategy of digestion
4.1.1 Carbohydrates
4.1.2 Fats
4.1.3 Proteins and amino acids
4.2 Stages of digestion. 4.2.1 The mouth
4.2.2 The stomach. 4.2.2.1 General description
4.2.2.2 Digestive processes in the stomach
4.2.2.3 Regulation of digestive processes in the stomach
4.2.3 The small intestine. 4.2.3.1 General description
Box 4.1 Malabsorption
4.2.3.2 Digestive processes occurring in the small intestine
4.2.3.2.1 Starch digestion
4.2.3.2.2 Protein digestion
4.2.3.2.3 Fat digestion
Box 4.2 The bile acids and salts
4.2.3.3 Regulation of digestive processes in the small intestine
4.3 Absorption from the small intestine. 4.3.1 Monosaccharides
4.3.2 Amino acids and peptides
4.3.3 Lipid absorption
4.3.4 Other processes occurring in the small intestine
4.4 The large intestine
Box 4.3 The human microbiota
SUPPLEMENTARY RESOURCES
Note
CHAPTER 5 Metabolic specialisation of organs and tissues. Key learning points
5.1 The liver. 5.1.1 General description of the liver and its anatomy
5.1.1.1 Liver metabolism
5.1.1.2 Carbohydrate metabolism in the liver
5.1.1.2.1 Fed conditions
Box 5.1 Hormonal regulation of glycogen breakdown (glycogenolysis) and synthesis (glycogenesis) in the liver. Glycogen breakdown
Glycogen synthesis
Box 5.2 The pathways of glycolysis and gluconeogenesis and their hormonal regulation. Pathways and abbreviations
Regulation
5.1.1.2.2 Fasted conditions
Box 5.3 Anaplerosis and cataplerosis: the ins and outs of the TCA cycle, and the enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase
5.1.1.2.3 The pentose phosphate pathway
5.1.1.3 Lipid metabolism in the liver
5.1.1.3.1 Fatty acid oxidation
5.1.1.3.2 Lipid synthesis
Box 5.4 Synthesis of fatty acids and cholesterol from glucose
Pathways and abbreviations
De novo lipogenesis and the production of non-essential fatty acids
Regulation
Box 5.5 Non-alcoholic fatty liver disease
5.1.1.3.3 Longer-term control of hepatic fat metabolism
5.1.1.3.4 Other roles of the liver in fat metabolism
5.1.1.4 Amino acid metabolism in the liver
5.2 Adipose tissue
5.2.1 White and brown adipose tissue
5.2.2 White adipose tissue metabolism
Box 5.6 Adverse consequences of excessive concentrations of lipids in the circulation
5.2.2.1 Lipid storage
5.2.2.2 Lipid mobilisation
5.2.2.3 Adipocyte differentiation and longer-term regulation of fat storage
5.2.3 Brown adipose tissue and the concept of ‘uncoupling’
5.2.3.1 Different types of brown adipocyte
5.2.3.2 Brown adipose tissue in humans
5.3 Skeletal muscle. 5.3.1 General description and structure of skeletal muscle
5.3.2 Metabolism of skeletal muscle: general features
5.3.3 Routes of ATP generation in skeletal muscle
5.3.3.1 Glucose metabolism in skeletal muscle
5.3.3.2 Fatty acid metabolism in skeletal muscle
Box 5.7 Lipid droplets
5.3.3.3 Amino acid metabolism in skeletal muscle
5.4 The heart
5.4.1 Cardiac substrate selection
5.4.2 Cardiac metabolism in heart disease
5.5 The kidneys. 5.5.1 General description
5.5.2 The scale of kidney function
5.5.3 Energy metabolism in the kidney
5.6 The brain
5.7 The endothelium – a large organ distributed throughout the body
5.8 Enterocytes
5.9 Cells of the immune system
SUPPLEMENTARY RESOURCES
Notes
CHAPTER 6 Communication systems. Key learning points
6.1 Communication systems
6.2 Hormones important in metabolic regulation
6.2.1 The pancreas. 6.2.1.1 General description of the pancreas
6.2.1.2 Insulin
6.2.1.3 Glucagon
6.2.2 The pituitary gland
6.2.2.1 Hormones of the anterior pituitary (adenohypophysis)
6.2.2.2 Hormones of the posterior pituitary (neurohypophysis)
6.2.3 The thyroid gland
6.2.4 The adrenal glands
6.2.4.1 The adrenal cortex: cortisol secretion
6.2.4.2 The adrenal medulla, adrenaline secretion, and adrenaline action
6.2.5 ‘Metabolic tissues’ that secrete hormones
6.2.5.1 Adipose tissue
6.2.5.2 Heart
6.2.5.3 Kidney
6.2.5.4 Skeletal muscle
6.2.5.5 The gastrointestinal tract
6.3 The nervous system and metabolism
6.3.1 Outline of the nervous system as it relates to metabolism. 6.3.1.1 The nerve cell
Box 6.1 The membrane potential and nerve impulses
Box 6.2 Synaptic transmission
6.3.1.2 Layout of the nervous system
6.3.2 Physiology of the nervous system
6.3.2.1 The brain
6.3.2.1.1 The hypothalamus
6.3.2.1.2 The cerebellum and brainstem
6.3.2.2 The autonomic nervous system. 6.3.2.2.1 The sympathetic nervous system
6.3.2.2.2 The parasympathetic nervous system
6.3.2.2.3 The somatic nervous system
6.3.2.3 Neurotransmitters and receptors
6.3.2.3.1 Adrenergic transmission
6.3.2.3.2 Cholinergic transmission
6.3.3 Major effects of adrenergic stimulation. 6.3.3.1 Stimuli for activation of the sympathetic nervous system and adrenal medulla
6.3.3.2 Metabolic effects of adrenergic activation
6.3.3.3 Circulatory effects of adrenergic activation
6.3.3.4 Effects of the autonomic nervous system on hormone secretion
SUPPLEMENTARY RESOURCES
Note
CHAPTER 7 Integration of carbohydrate, fat and protein metabolism in normal daily life. Key learning points
7.1 The body’s fuel stores
7.1.1 Carbohydrate
7.1.2 Fat
7.1.3 Amino acids
7.2 Carbohydrate metabolism
7.2.1 The overnight-fasted (postabsorptive) state
7.2.2 Breakfast
7.2.2.1 Carbohydrate metabolism in the liver after breakfast
7.2.2.2 Carbohydrate metabolism in other tissues after breakfast
7.2.2.3 Disposal of glucose after a meal
7.3 Lipid metabolism
7.3.1 Plasma non-esterified fatty acids
7.3.2 Plasma triacylglycerol
7.3.3 The overnight-fasted state
Box 7.1 Glucose and lipids as energy sources
7.3.4 Breakfast
7.3.4.1 Non-esterified fatty acid metabolism after breakfast
7.3.4.2 Triacylglycerol
7.4 Amino acid and protein metabolism. 7.4.1 General features
7.4.2 Some particular aspects of amino acid metabolism. 7.4.2.1 Essential and non-essential amino acids, and other metabolically distinct groups of amino acids
7.4.2.2 Branched-chain amino acids and muscle amino acid metabolism
7.4.2.3 Alanine and glutamine
7.4.3 The overall control of protein synthesis and breakdown
7.5 Links between carbohydrate, lipid, and amino acid metabolism
7.5.1 Carbohydrate and lipid metabolism. 7.5.1.1 Lipogenesis
Box 7.2 The physiological importance of de novo lipogenesis in humans on a Western diet
7.5.1.2 Metabolic interactions between fatty acids and glucose: the glucose–fatty acid cycle
Box 7.3 The glucose–fatty acid cycle
7.5.2 Interactions between carbohydrate and amino acid metabolism: the glucose–alanine cycle and gluconeogenesis from amino acids
7.6 Blood flow and the integration of metabolism
7.7 An integrated overview of metabolism: a metabolic diary
7.7.1 The postabsorptive state: waking up
7.7.2 A lazy day. 7.7.2.1 Breakfast goes down
7.7.2.2 Another meal follows
7.7.3 An energetic day
7.7.4 Effect of the diurnal cycle on metabolism
7.8 Metabolic control in a physiological setting
SUPPLEMENTARY RESOURCES
Notes
CHAPTER 8 Metabolic challenges: Coping with some extreme physiological situations. Key learning points
8.1 Situations in which metabolism is significantly altered from its normal pattern
8.2 Exercise
8.2.1 Types of exercise
8.2.2 Intensity of exercise
Box 8.1 Measurement of power by climbing stairs
Notes
Box 8.2 Energy expenditure
Box 8.3 Does a confectionery bar provide enough energy to climb a mountain?
8.2.3 Metabolic regulation during anaerobic exercise
Box 8.4 Events occurring in skeletal muscle on receipt of a somatic nerve impulse
Box 8.5 Activation of the pathway of glycolysis at the start of anaerobic exercise
Allosteric regulation
Substrate cycling
8.2.4 Metabolic regulation during aerobic exercise
Box 8.6 How much ATP is used in running a marathon?
8.2.5 Nervous system and cardiovascular responses during aerobic exercise
8.2.6 Other hormonal responses during aerobic exercise
8.2.7 Carbohydrate metabolism during endurance exercise
8.2.8 Fat metabolism during endurance exercise
8.2.9 The effects of training
8.3 Growth and development. 8.3.1 Metabolism in early (foetal and neonatal) development. 8.3.1.1 Foetal metabolism
8.3.1.2 Birth-suckling transition
8.3.1.3 Neonatal metabolism
8.3.2 Pregnancy
Box 8.7 Carbohydrate metabolism in pregnancy
8.3.3 Lactation
SUPPLEMENTARY RESOURCES
Notes
CHAPTER 9 Metabolic challenges: Coping with some pathological situations. Key learning points
Pathological challenges to metabolism
9.1 Starvation
9.1.1 The early phase
9.1.2 The period of adaptation to starvation
9.1.2.1 Hormonal changes
9.1.2.2 Adaptation of fatty acid, ketone body, and glucose metabolism
9.1.2.3 Sparing of muscle protein
9.1.2.4 Kidney metabolism
9.2 The period of adapted starvation
9.3 Pathological stress: the metabolic response to tissue injury and the effects of inflammation, infection and trauma
9.3.1 Response to trauma
9.3.2 Response to infection
9.3.3 SIRS and MODS
9.4 Cancer metabolism
9.4.1 Tumour cell metabolism
9.4.1.1 Altered pathways
9.4.1.2 Oncometabolites
9.4.2 Host metabolism in cancer – cancer cachexia
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CHAPTER 10 Lipoprotein metabolism and atherosclerosis. Key learning points
10.1 Introduction to lipoprotein metabolism
Box 10.1 The major apolipoproteins involved in lipoprotein metabolism
Apolipoproteins AI, AII and AIV
Apolipoprotein B
Apolipoproteins CI, CII and CIII
Apolipoprotein E
Box 10.2 Some important enzymes involved in lipoprotein metabolism. Lipoprotein Lipase (LPL)
Hepatic Lipase (HL)
Lecithin-Cholesterol AcylTransferase (LCAT)
Acyl-Coenzyme A: Cholesterol AcylTransferase (ACAT)
10.2 Outline of the pathways of lipoprotein metabolism. 10.2.1 Chylomicron metabolism: the exogenous pathway
10.2.2 VLDL and LDL metabolism. 10.2.2.1 VLDL metabolism: the endogenous pathway
10.2.2.2 LDL metabolism and regulation of cellular cholesterol content
Box 10.3 The LDL receptor and regulation of cellular cholesterol content
10.2.3 HDL metabolism
Box 10.4 Cholesterol homeostasis in the body
10.2.3.1 HDL and reverse cholesterol transport
10.2.3.2 Cholesteryl ester transfer protein
10.3 Regulation of lipoprotein metabolism
10.3.1 Insulin and triacylglycerol metabolism
10.3.2 Relationship between plasma triacylglycerol and HDL-cholesterol concentrations
10.3.3 Cholesterol homeostasis
10.4 Disturbances of lipoprotein metabolism. 10.4.1 Cholesterol and atherosclerosis
10.4.2 Conditions leading to elevation of the blood lipid concentrations
10.4.2.1 Primary hyperlipoproteinaemias
10.4.2.2 Secondary hyperlipidaemias and their treatment
Box 10.5 Dietary influences on the serum cholesterol concentration. Dietary cholesterol
Dietary fatty acids
10.4.3 HDL-cholesterol, plasma triacylglycerol, and coronary heart disease
Box 10.6 The atherogenic lipoprotein phenotype
Supplementary resources
CHAPTER 11 Energy balance and body weight regulation. Key learning points
11.1 Energy balance and body weight
11.2 Energy balance
11.2.1 Energy intake
Box 11.1 Regulation of energy intake
11.2.2 Energy expenditure. 11.2.2.1 Measurement of energy expenditure
Box 11.2 The principles of indirect calorimetry
Glucose
Fat
Protein
Box 11.3 Measurement of energy expenditure using double-labelled water
11.2.2.2 The components of energy expenditure
11.3 Conditions of low body weight. 11.3.1 Cachexia
11.3.2 Lipodystrophy
11.4 Obesity. 11.4.1 Definition of obesity
11.3.5 How does obesity develop?
11.4.3 Health implications of obesity
11.4.4 Metabolic changes in obesity
Box 11.4 Insulin resistance and the ‘metabolic syndrome’
11.5 Treatment of obesity. 11.5.1 Dieting from the viewpoint of metabolic regulation
11.4.2 Pharmacological treatment of obesity
Supplementary resources
Note
CHAPTER 12 Diabetes mellitus. Key learning points
12.1 Different types of diabetes
12.2 Clinical features of diabetes. 12.2.1 History of diabetes
12.2.2 Type 1 diabetes mellitus
12.2.3 Type 2 diabetes mellitus
12.3 Metabolic alterations in diabetes mellitus
12.3.1 Glucose tolerance
Box 12.1 Diagnosis of diabetes mellitus
12.3.2 Untreated Type 1 diabetes
12.3.3 Metabolic alterations in Type 2 diabetes
12.4 Treatment of diabetes mellitus. 12.4.1 Type 1 diabetes
12.4.2 Type 2 diabetes
12.5 The longer-term complications of diabetes. 12.5.1 Macrovascular and microvascular disease and their relationship to glucose concentrations
12.5.2 Non-enzymatic glycation of proteins
12.5.3 The polyol pathway
12.5.4 The hexosamine pathway
12.5.5 Protein kinase C activation
12.5.6 A common pathway?
12.6 Prevention of diabetes
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Note
Index
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