491 Crash Course Metabolism and Nutrition 4e Dr Zaheer

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Front Cover 
	Crash Course: Metabolism and Nutrition
	Copyright
	Series editor foreword
	Prefaces
	Authors
	Faculty Advisor
	Acknowledgements
	Contents
	Chapter 1: Introduction to metabolism
	Introductory concepts
	Metabolism
	Enzymes
	Enzyme nomenclature
	Anabolism and catabolism
	Pathway regulation
	Substrate availability
	Allosteric regulation
	Phosphorylation
	Hormonal regulation
	Membrane traffic
	Symports (`co-transports´) and antiports
	Active and passive transport
	Primary active transport
	Secondary active transport
	Bioenergetics
	Redox reactions
	Reduction and oxidation
	Free radicals
	Key players
	Adenosine triphosphate (ATP): Cellular `energy currency´
	Roles of ATP
	Sources of ATP
	NAD+ and FAD
	Role of NAD+ and FAD in ATP generation
	NADP+
	Acetyl CoA
	Chapter 2: Energy metabolism I
	The tricarboxylic acid (TCA) cycle
	Role in metabolism
	Energy yield of the TCA cycle
	Regulation of the TCA cycle
	Allosteric regulation
	Substrate provision/`respiratory control´
	TCA cycle intermediates as precursors
	Anaplerotic reactions
	TCA-generated reducing equivalents enter the electron transport system
	Chapter 3: Energy metabolism II
	ATP generation
	Substrate-level phosphorylation
	Oxidative phosphorylation
	The electron transport chain (ETC)
	Electron pairs: where do they come from?
	Electron pair transfer between ETC complexes
	Generation of the proton gradient
	Different ATP generation capacity of NADHH and FADH2
	ATP synthesis
	ATP synthase (complex V)
	The term `coupling´
	Sources of NADHH and FADH2
	ETC complexes: why do they readily accept and then transfer onward incoming electron pairs?
	Transfer of NADHH: from cytoplasm to the mitochondria
	Glycerol-3-phosphate shuttle
	Malate-aspartate shuttle
	NAD+ regeneration
	Uncoupling
	Chapter 4: Carbohydrate metabolism
	Carbohydrates: A definition
	Glucose entry into cells
	Facilitated diffusion
	Secondary active transport
	Glycolysis
	Overview
	Glycolysis: the reaction pathway
	`Energy investment´ phase
	`Energy generation´ phase
	Glycolytic intermediates as biosynthetic precursors
	Regulation of glycolysis
	Reaction 1: Glucose phosphorylation
	Reaction 3: Fructose-6-phosphate phosphorylation
	Reaction 10: Phosphoenolpyruvate pyruvate
	The insulin:glucagon ratio influence on glycolysis
	Aerobic glycolysis vs. anaerobic glycolysis
	Hyperlactataemia
	Hereditary red cell enzymopathies
	The pyruvate acetyl CoA reaction
	Pyruvate dehydrogenase
	Regulation of PDH
	Gluconeogenesis
	Necessity of a synthetic pathway for glucose
	Timescale of glycogenolysis vs. gluconeogenesis
	Gluconeogenesis substrates
	Sequence of reactions
	Key differences between gluconeogenesis and glycolysis
	Regulation of gluconeogenesis
	Reaction 1: Pyruvate oxaloacetate (carboxylation)
	Reaction 2: Oxaloacetate phosphenolpyruvate (decarboxylation)
	Reaction 9: Fructose-1,6-bisphosphate fructose-6-phosphate (hydrolysis)
	Reaction 11: Glc-6-P glucose (hydrolysis)
	Glycogen metabolism
	Glycogen stores
	Glycogen structure
	Glycogen synthesis (glycogenesis)
	Stage I: Formation of glucose-1-phosphate (Glc-1-P)
	Stage II: Formation of `activated´ glucose (UDP-glucose)
	Stage III: Elongation
	Stage IV: Branch formation
	Glycogen breakdown (`glycogenolysis´)
	Strand shortening
	Branch removal
	Regulation of glycogen metabolism
	Hormonal control
	Allosteric regulation
	Hepatic glycogen
	Muscle glycogen
	Glycogen storage diseases
	The pentose phosphate pathway (PPP)
	Processing of dietary pentose sugars
	Reactions of the PPP
	Regulation of the PPP
	Glutathione
	Mechanism of action of glutathione
	Role of glutathione in drug metabolism
	Glutathione in erythrocytes
	Glutathione: the γ-glutamyl cycle
	Glucose-6-phosphate dehydrogenase deficiency; the failure of the PPP
	Precipitating factors
	Fructose, Galactose, Sorbitol and Ethanol
	Fructose metabolism
	Genetic deficiencies of fructose metabolism
	Fructokinase deficiency
	Fructose-1-phosphate aldolase deficiency (aldolase B)
	Fructose-6-phosphate
	Galactose metabolism
	Galactose Glucose-6-phosphate
	Galactosaemia
	Sorbitol metabolism
	Ethanol metabolism
	Enzyme systems
	Mitochondrial processing
	Ethanal toxicity
	Impact of ethanol catabolism
	Ethanol influence on drug metabolism
	Chapter 5: Lipid transport and metabolism
	Lipids: an introduction
	Definition
	Lipid roles
	Fatty acids: archetype lipids
	Fatty acids in metabolism
	Fatty acids: the suffixes `-ic acid´ and `-ate´
	Saturated vs. unsaturated
	Stereoisomerism: cis and trans configurations of the C=C double bond
	Naming organic molecules
	Fatty acid biosynthesis
	Introduction
	Overview of fatty acid synthesis
	Details of fatty acid synthesis
	1. Transport of acetyl CoA from mitochondria to cytoplasm
	2. Conversion of acetyl CoA to malonyl CoA
	Getting it together: assembly of malonyl and acetyl groups on ACP
	Fatty acid synthase (FAS)
	3. Condensation
	Reduction, dehydration, reduction. . .
	`Site switch´ of the growing chain
	4. Addition of further malonyl CoA
	Transfer of the lengthened acyl chain onto malonyl-ACP
	Elongation to palmitate
	Elongation of fatty acids beyond 16 carbons
	Desaturation of fatty acids
	Essential fatty acids
	Regulation of fatty acid synthesis
	Substrate availability: malonyl CoA
	Substrate availability: NADPH+H+
	Substrate availability: hormonal regulation
	Lipogenesis: triacylglycerol synthesis
	Lipid catabolism
	1. Lipolysis
	Fate of liberated fatty acids
	Fate of liberated glycerol
	2. Fatty acid activation
	3. Accessing the mitochondrial matrix: the carnitine shuttle
	4. β-oxidation of fatty acids
	(1). Oxidation by FAD
	(2). Hydration
	Oxidation by NAD+
	(4). Thiolysis: release of acetyl CoA
	Reiteration of 1→4
	Odd-chain fatty acids
	Propionyl CoA
	ATP yield from fatty acid oxidation
	ATP yield from β-oxidation of odd-numbered fatty acids
	Oxidation of unsaturated fatty acids
	Peroxisomal -oxidation
	Regulation of lipid breakdown
	Regulation of lipolysis
	Regulation of mitochondrial access
	Availability of NAD+ and FAD
	Abnormalities of fatty acid metabolism
	Cholesterol metabolism
	Molecular features
	Physiological roles of cholesterol
	Cholesterol synthesis
	Stage I: formation of isopentyl pyrophosphate (IPP)
	Stage II: Progressive assimilation of isoprene units to form squalene
	Stage III: Further conversions: squalene cholesterol
	Regulation of cholesterol synthesis
	Product-mediated inhibition
	Hormonal regulation
	Lipid transport
	Lipoproteins
	Lipoprotein classes
	Lipid processing
	Exogenous lipids
	1. Chylomicron formation
	2. Chylomicron circulation
	3. Peripheral hydrolysis of chylomicron triacylglycerol cargo
	4. Loss of CII apoproteins: remnant generation
	Endogenous lipids
	1. VLDL assembly
	2. LPL hydrolysis of VLDL cargo
	3. IDL and LDL formation
	4. Cholesterol offloading at periphery
	HDL metabolism
	Cholesterol: modification for transport
	Excess cellular cholesterol elimination
	Cellular cholesterol clearance
	Genetic dyslipidaemias
	Familial hypercholesterolaemia
	Familial chylomicronaemia
	Acquired hypercholesterolaemia
	Ketones and ketogenesis
	Ketone synthesis
	Formation of acetoacetate
	Acetoacetate conversion to acetone or 3-hydroxybutyrate
	Regulation of ketone synthesis
	High rate of gluconeogenesis
	High lipid catabolism activity
	Important clinical examples of metabolic states promoting ketone synthesis
	Starvation
	Type 1 diabetes: diabetic ketoacidosis
	Ketoacidosis
	Ketone catabolism
	Ketone utilization in the CNS
	Ketone utilization in cardiac myocytes
	Chapter 6: Protein metabolism
	Protein structure
	Amino acids
	Key reactions in amino acid metabolism
	Transamination: conversion of any amino acid into alanine, glutamate
or aspartate
	Oxidative deamination: removal of the amino group
	Amino acid transport
	γ-glutamyl cycle
	Amino acid synthesis
	`Essential´ and `non-essential´ amino acids
	Glutamate, glutamine, proline and arginine biosynthesis
	Glutamate biosynthesis
	Glutamine biosynthesis
	Proline biosynthesis
	Arginine biosynthesis
	Aspartate and asparagine biosynthesis
	Serine, glycine and cysteine biosynthesis
	Serine biosynthesis
	Glycine biosynthesis
	Cysteine biosynthesis
	Tyrosine biosynthesis
	Alanine biosynthesis
	Biological derivatives of amino acids
	Serotonin synthesis from tryptophan
	Adrenaline, noradrenaline and dopamine synthesis from tyrosine
	Thyroid hormone synthesis from tyrosine
	Nitrogen balance
	Amino acid catabolism
	Removal of the amino group
	Transdeamination: removal of the amino group as NH3
	Transamination: incorporation of the amino group into aspartate
	Catabolism of carbon skeletons
	The terms `glucogenic´ and `ketogenic´
	Branched-chain amino acids (BCAA)
	The urea cycle
	Fate of urea cycle fumarate
	Sources of urea cycle aspartate
	Vital metabolic role of the urea cycle
	Regulation of the urea cycle
	Abnormalities of the urea cycle
	Protein synthesis and degradation
	Protein turnover
	Protein degradation
	Ubiquitination
	Lysosomal proteolysis
	Intracellular degradation signals
	N-terminus components
	`PEST´ regions
	Protein synthesis: translation
	Protein synthesis: transcription
	Chapter 7: Purines, pyrimidines and haem
	One-carbon pool
	One-carbon units
	S-adenosyl methionine
	Folate
	Folate metabolism
	Formation of THF
	Methyl-folate trap (Fig. 7.3)
	Amino acids and the one-carbon pool
	Formation of SAM from methionine (numbers refer to Fig. 7.3)
	Purine metabolism
	Structure and function of purines
	An overview of purine metabolism
	I. De novo synthesis of purines
	II. Salvage pathways
	Regulation of purine biosynthesis
	Breakdown of purines
	1. Breakdown of the nucleotide to a free base: hypoxanthine or xanthine
	2. Formation of uric acid
	Xanthine oxidase inhibitors
	Gout
	Symptoms of gout
	Causes of gout
	Genetic
	Secondary causes
	Treatment of gout
	Lesch-Nyhan syndrome
	Pyrimidine metabolism
	Structure and function of pyrimidines
	Structure
	Functions
	Biosynthesis of pyrimidines
	Regulation of pyrimidine synthesis
	Regulation of deoxyribonucleotide synthesis
	Salvage pathways
	Breakdown of pyrimidines
	Anti-cancer drugs
	Haem metabolism
	Structure and function of haem
	Structure
	Functions
	Haem biosynthesis
	Site
	An overview of the pathway
	Regulation of haem synthesis
	Induction of ALA synthase in the liver
	Haem breakdown
	Location/site
	Pathway
	Bilirubin metabolism
	The porphyrias
	Acute intermittent porphyria
	Clinical features
	Results of laboratory tests
	Management
	Overall management
	Lead poisoning
	Treatment
	Chapter 8: Glucose homeostasis
	The states of glucose homeostasis
	The fed state
	The fasted state
	The starved state
	Early starved state
	Late starved state
	Gluconeogenesis
	Ketogenesis
	Hormonal control of glucose homeostasis
	Glucose homeostasis in exercise
	Sprinters
	Long-distance running
	Mechanism of action of insulin
	Diabetes mellitus
	Classification
	Type 1 diabetes mellitus
	Type 2 diabetes mellitus
	Other types of diabetes
	Metabolic effects of diabetes mellitus
	Type 1 diabetes mellitus
	Type 2 diabetes mellitus
	Symptoms of diabetes mellitus
	Acute
	Subacute
	Asymptomatic
	Diabetic ketoacidosis
	Complications
	Clinical features
	Type 1 diabetes mellitus
	Type 2 diabetes mellitus
	Complications of diabetes
	Acute complications (fig 8.15)
	Hypoglycaemia
	Diabetic ketoacidosis (DKA)
	Chronic complications
	Chapter 9: Digestion, malnutrition and obesity
	Basic principles of human nutrition
	Definitions
	Nutrients
	Staple foods
	Digestion in the gastrointestinal tract
	Digestion of carbohydrates
	Digestion of proteins
	Digestion of fats
	Methods of estimating an individual's dietary intake
	Dietary reference values
	Energy balance
	Food energy
	Body composition
	Energy requirements
	Basal metabolic rate
	Thermic effect of food
	Physical activity
	How do we measure energy requirements?
	Indirect calorimetry
	Indirect mass spectrophotometry
	Regulation of food intake
	Key hormones/signals:
	Obesity
	Definition
	Aetiology
	Clinical consequences
	Prevention and treatment
	Proteins and nutrition
	Definitions
	Reference proteins
	Limiting amino acids
	Protein quality
	Chemical score
	Biological value
	Net protein utilization
	Net dietary protein as a percentage of energy
	Protein requirement
	Protein-energy deficiency states
	Causes of PEM
	Incidence
	Aetiology and mechanisms of pathogenesis
	Marasmus
	Kwashiorkor
	Management and treatment of PEM
	Prognosis
	Consequences of prolonged PEM
	Prevention
	Parenteral and enteral nutrition
	Administration
	Monitoring the patient
	Chapter 10: Nutrition
	Vitamins
	Definition
	Fat-soluble vitamins
	Water-soluble vitamins
	Fat-soluble vitamins
	Vitamin A (retinol)
	RNI
	Absorption and transport of vitamin A
	Functions
	Deficiency
	Incidence
	Causes
	Clinical features
	Diagnosis and treatment
	Teratogenicity
	Vitamin D3 (cholecalciferol)
	RNI
	Sources
	Synthesis
	Functions
	Mechanism of action
	Deficiency
	Groups at risk of deficiency
	Clinical features and pathogenesis
	Vitamin E (tocopherol)
	RNI
	Sources
	Absorption and transport
	Functions and deficiency
	Deficiency
	Incidence
	Clinical features
	Vitamin K
	RNI
	Sources
	Functions and deficiency
	Deficiency
	Causes
	Mechanism
	Diagnosis and treatment
	Deficiency in newborn babies
	Water-soluble vitamins
	Vitamin B1 (thiamine)
	RNI
	Sources
	Active form
	Functions
	Deficiency diseases
	Beriberi
	Incidence
	Diagnosis
	Treatment
	Wernicke-Korsakoff syndrome
	Incidence
	Toxicity
	Vitamin B2 (riboflavin)
	RNI
	Sources
	Active forms
	Functions and deficiency
	Niacin or nicotinic acid
	RNI
	Sources
	Synthesis of niacin from tryptophan
	Active forms
	Functions and deficiency
	Pellagra: a disease of the skin, gastrointestinal tract and central nervous system
	Incidence
	Causes
	Diagnosis
	Treatment
	Toxicity
	Vitamin B6
	RNI
	Sources
	Active form
	Functions and deficiency
	Pyridoxine deficiency
	Causes
	Clinical features
	Treatment
	Toxicity
	Pantothenic acid
	Sources
	Active form
	Functions and deficiency
	Biotin
	Vitamin B12 (cobalamin)
	RNI
	Sources
	Active forms
	Absorption and transport
	Functions
	Deficiency and toxicity
	Causes of deficiency
	Pernicious anaemia
	Incidence
	Pathogenesis
	Diagnosis
	Treatment
	Folate
	RNI
	Sources
	Active form
	Absorption and storage
	The role of folate and vitamin B12
	Functions and deficiency
	Folate deficiency
	Causes
	Clinical features and diagnosis of folate deficiency
	Treatment
	Folate deficiency in pregnancy
	A comparison of folate and vitamin B12 deficiencies
	Vitamin C (ascorbate)
	RNI
	Sources
	Active form
	Functions and deficiency
	Vitamin C deficiency: scurvy
	Causes
	Clinical features
	Treatment
	The megadose hypothesis
	Toxicity
	Symptoms of vitamin deficiencies
	Fat-soluble vitamins: A, D, E and K
	Water-soluble vitamins (B and C)
	Chapter 11: Nutrition
	Classification of minerals
	Calcium
	RNI
	Sources
	Absorption
	Active forms
	Main functions
	Regulation of calcium
	Calcium deficiency
	Pathogenesis
	Calcium overload: hypercalcaemia
	Causes
	Clinical features
	Phosphorus
	RNI
	Sources
	Functions
	Deficiency and toxicity
	Magnesium
	RNI
	Sources
	Functions
	Deficiency
	Excess
	Sodium, potassium and chloride
	Sulphur
	Iron
	RNI
	Sources
	Absorption, transport and storage
	Iron
deficiency anaemia
	Bioavailability
	Causes of deficiency
	Inadequate intake
	Increased requirement
	Blood loss
	Malabsorption
	Groups in the population at risk of deficiency
	Clinical features and diagnosis of iron deficiency anaemia
	Management and treatment
	Prognosis
	Iron overload
	Causes
	Idiopathic primary haemochromatosis
	Pathogenesis
	Clinical consequences
	Treatment
	Transfusional iron overload: transfusion siderosis
	Causes
	Treatment
	Zinc
	Zinc deficiency
	Acrodermatitis enteropathica
	Treatment
	Copper
	RNI
	Sources
	Copper metabolism
	Function
	Copper deficiency: Menkes´ kinky hair syndrome
	Treatment
	Copper overload: Wilson's disease
	Aetiology
	Treatment
	Iodine
	Deficiency
	Endemic goitre
	Pathogenesis of goitre
	Cretinism
	Iodine overload
	Other trace elements
	Symptoms of mineral deficiencies
	Chapter 12: Clinical assessment of metabolic and nutritional disorders
	Presentation of metabolic and nutritional disorders
	Common presenting complaints
	Fatigue
	Weight loss
	Working definition
	Symptoms of anaemia
	Causes of anaemia
	Dehydration
	Symptoms and signs
	Fluid overload
	Symptoms of amino acid disorders
	History taking
	Things to remember when taking a history
	Structure of a history
	Personal information
	Presenting complaint (PC)
	History of presenting complaint (HPC)
	Review of symptoms
	Cardiovascular system, ask specifically about:
	Respiratory system, ask specifically about
	Gastrointestinal system, ask specifically about
	Urinary system, ask specifically about
	Skin, ask specifically about
	Musculoskeletal system, ask specifically about
	Nervous system, many questions so use a structure
	Menstruation and obstetric history
	Past medical history (PMHx)
	Drug history (DH)
	Allergies
	Smoking
	Alcohol
	Family history (FH)
	Social history (SH)
	Summarize
	Communication skills
	The importance of communication
	Obstacles to communication
	Verbal communication skills
	Non-verbal communication skills
	Objectives in the consultation
	Physical examination
	General inspection
	Limbs
	Main metabolic problems to consider in examination of the limbs
	Hands
	Skin manifestations of dyslipidaemias
	Gout
	Head and neck
	Face
	Neck
	Thyroid disease
	Thorax
	Respiratory system
	Checklist for examination of the respiratory system (Figs 12.12 and 12.13)
	Cardiovascular system
	Inspection and palpation
	Percussion
	Auscultation
	Abdomen
	Useful points for the examination of the abdomen
	Inspection
	Palpation
	Percussion
	Auscultation
	Summary
	Further investigations
	Routine investigations
	Haematology
	Clinical chemistry
	Urine
	Histopathology
	Immunopathology
	Medical imaging
	Investigation of glucose homeostasis
	Measurement of blood glucose
	Use
	Test
	Method
	Advantages
	Fasting blood glucose
	Use
	Method
	Oral glucose tolerance test
	Use
	Method
	Assessment of glycaemic control: glycated haemoglobin
	Use
	Method
	Investigation of lipid metabolism
	Cholesterol and triacylglycerol (triglyceride) concentration
	Uses
	Investigations
	Enzymes as tissue markers
	Glucose-6-phosphate dehydrogenase
	Use
	Pyruvate kinase assay
	Use
	Test
	Reference values
	Galactose and fructose
	Galactosaemia
	Tests
	Fructokinase deficiency: essential fructosuria
	Hormone assays
	Thyroid-stimulating hormone
	Other investigations
	Diagnosis of phenylketonuria
	Screening test
	Assessment of nutritional status
	Medical, social and dietary history
	Medical history
	Social history
	Dietary history
	Dietary recall
	Anthropometric measurements
	Physical clinical examination in disorders of nutrition
	Clinical signs
	Biochemical tests
	Types of biochemical tests
	Direct measurement
	Measurement of stores
	Genetic testing
	Best-of-five questions (BOFs)
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	Chapter 8
	Chapter 9
	Chapter 10
	Chapter 11
	Chapter 12
	History and examination
	Further investigations
	Extended-matching questions(EMQs)
	BOF answers
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	Chapter 8
	Chapter 9
	Chapter 10
	Chapter 11
	Chapter 12
	History and examination
	Further investigations
	EMQ answers
	Glossary
	References
	Chapter 8
	Chapter 9
	Obesity resources
	Refeeding syndrome resources
	Chapter 12
	Index