Basic Sciences for Dental Students E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 550

Veröffentlichungsjahr: 2017

Beschreibung

The ‘all-in-one’ solution to mastering basic sciences in preclinical dentistry

Basic Sciences for Dental Students is a cutting edge textbook specifically designed to support the needs of early years undergraduate dental students. Written by leaders in dental education and active oral and dental researchers involved with student assessment, the text explains the basic science that underpins the dental curriculum in undergraduate dental courses worldwide.

Specifically related to dentistry and future clinical practice, chapters cover all of the introductory subjects that students need to know – biomolecules, cell biology, tissues of the body, cardiovascular, circulatory and pulmonary systems, the nervous system, immunology, oral microbiology, pathology, head and neck anatomy, tooth development, craniofacial development, saliva, and dental materials.

Key features:

• Provides the basic science that underpins the early years of a dental curriculum
• Specifically tailored towards dentistry and future clinical practice
• Written by leaders in dental education and active oral and dental researchers
• Includes learning objectives and clinical relevance boxes throughout
• Self-assessment questions and downloadable figures are hosted on a companion website

Basic Sciences for Dental Students is an indispensable resource for undergraduate dental students, especially those in the early years of their studies. It is also a useful revision tool for postgraduate MJDF and MFDS examinations and overseas candidates sitting their OREs.

Leseprobe

Table of Contents

Cover

Title Page

List of Contributors

About the Companion Website

1 Biomolecules

Introduction

Biological Bonding

Water, Water Everywhere

Amino Acids and Proteins

Enzymes

Nucleic Acids

Carbohydrates

Lipids

2 Cell Biology

Introduction

The Plasma Membrane

Membrane Proteins

Subcellular Organelles

Life and Death of a Cell

3 Tissues of the Body

Epithelia

Connective Tissues

Muscle

4 The Cardiovascular, Circulatory and Pulmonary Systems

Introduction

Cardiac System

Circulatory System

The Pulmonary System

5 The Nervous System

Introduction

Subdivisions of the Nervous System

Structural Components of the Nervous System

Anatomical Organization of Peripheral Somatic Nerves and Spinal Cord

The Autonomic Nervous System

Anatomy of the Brain

Summary of Brain Anatomy and Function

6 Introduction to Immunology

Introduction

Physical and Chemical Barriers to Infection

Microbiological Barriers to Infection

Molecular Elements of Innate Immunity: Antimicrobial Peptides and Complement

Cellular Elements of Innate Immunity

Innate Immune Signalling: Pattern Recognition, Chemotaxis and the Interferon Response

Adaptive Immunity I: B‐cells and Antibodies

Adaptive Immunity II: Antigen Presentation and T‐cell Activation

Inflammation

Immune Responses During Infection

Malfunctions of the Immune System

Vaccination

7 Oral Microbiology

Introduction

Oral Microbiota

Microbial Communities in the Mouth

Microbiology of Caries

Microbiology of Periodontal Diseases

Other Oral Infections

Summary

8 Introduction to Pathology

Introduction

Aetiology of Disease

Mechanisms of Disease

Inflammation

9 Head and Neck Anatomy

The Cranial Nerves

The Face and Neck

The Temporomandibular Joint

Muscles of Mastication

The Oral Cavity

The Pharynx and Larynx

The Orbit

The Paranasal Air Sinuses

10 Tooth Development, Tooth Morphology and Tooth‐Supporting Structures

Introduction

Early Tooth Development

Late Tooth Development

Dentinogenesis

Dentine Mineralization

Tooth Root Formation

Epithelial–Mesenchymal Interactions in Tooth Development

Amelogenesis

Enamel Mineralization

Tooth Morphology

Development of the Tooth‐Supporting Structures

11 Craniofacial Development

Introduction

Jaws and Support Skeleton

The Temporomandibular Joint

Cranial and Facial Sutures

The Tongue

The Palate

Craniofacial Syndromes

12 Saliva and Salivary Glands

Introduction

Salivary Gland Anatomy and Structure

How is Saliva Formed by Salivary Glands?

The Composition and Functions of Saliva

13 Introduction to Dental Materials

Introduction

The Structure of Matter

The Nature of Materials and Examples in Dentistry

Physical and Mechanical Properties

Safety, Biocompatibility and Adverse Reactions

Conclusions

Index

End User License Agreement

List of Tables

Chapter 06

Table 6.1 Physical barriers and chemical agents against infection and their properties.

Table 6.2 Host defences in the saliva.

Table 6.3 Phagocytic cells of the immune system and their function.

Table 6.4 Pattern‐recognition receptors and the ligands (and microorganisms) they recognize.

Table 6.5 The major families of cytokines and their functions.

Table 6.6 Function of immunoglobulin classes and subclasses.

Table 6.7 Processes which lead to self tolerance.

Table 6.8 CD4+ T‐cell subsets and their immunological function.

Table 6.9 Physical characteristics of acute inflammation.

Table 6.10 Conditions of immunodeficiency, their cause and symptoms.

Table 6.11 Some autoimmune diseases and their characteristics.

Table 6.12 Hypersensitivity reactions and their pathogenesis.

Table 6.13 UK vaccination programme for all.

Table 6.14 Vaccinations for special groups.

Chapter 07

Table 7.1 Predominant microbial genera found within the oral cavity.

Table 7.2 Oral streptococci.

Table 7.3 Types of dental caries.

Table 7.4 Classification of periodontal diseases.

Table 7.5 Types of oral candidosis.

Chapter 08

Table 8.1 Environmental causes of disease.

Table 8.2 Characteristics of different types of neoplasm.

Chapter 09

Table 9.1 Clinical tests for cranial nerve function.

Chapter 10

Table 10.1 Tooth morphology and anatomical features of the permanent dentition.

Table 10.2 Calcification and eruption dates for the deciduous dentition.

Table 10.3 Calcification and eruption dates for the permanent dentition.

Chapter 12

Table 12.1 Saliva composition and diagnostics.

Table 12.2 Rate of salivary flow from different glands.

List of Illustrations

Chapter 01

Figure 1.1 The chemical structure of water.

Figure 1.2 (a) Peptide bond and (b) amino acid ionization.

Figure 1.3 Classification of amino acids. Note that amino acids can be referred to using one‐ or three‐letter codes. This figure uses the former; so C represents cysteine, which in the three‐letter code would be Cys. SH is the thiol group of cysteine that can react to form a disulphide bridge (represented elsewhere by S–S) with another cysteine residue.

Figure 1.4 Three‐dimensional structure of salivary amylase.

Figure 1.5 Enzyme–substrate complexes and the transition state.

Figure 1.6 Mechanisms of enzyme inhibition. (a) Competitive inhibition. (b) Non‐competitive inhibition.

Figure 1.7 Allosteric regulation of protein kinase A.

Figure 1.8 The structure of the four nucleotides of DNA.

Figure 1.9 Nucleotides form antiparallel chains.

Figure 1.10 The structure of glucose.

Figure 1.11 Protein glycosylation.

Figure 1.12 Glycolysis.

Figure 1.13 The TCA cycle.

Figure 1.14 ATP structure and function.

Figure 1.15 Oxidative phosphorylation and ATP synthesis.

Figure 1.16 Regulation of phosphofructokinase.

Figure 1.17 Structure of fatty acids and triacylglycerols.

Figure 1.18 Absorption of lipids and packaging.

Figure 1.19 Production and fate of lipoproteins. For other definitions see text.

Figure 1.20 Fatty acid oxidation.

Figure 1.21 Gluconeogenesis.

Chapter 02

Figure 2.1 The basic structure of the plasma membrane.

Figure 2.2 The cell surface.

Figure 2.3 Types of membrane transport.

Figure 2.4 Membrane receptors. Diagram shows a kinase‐associated receptor. Phosphorylation (P) of the intracellular domain causes recruitment of STAT proteins which are then able to move to the nucleus to cause transcription of specific genes

Figure 2.5 The diagram shows a membrane‐bound enzyme (depicted as a Pacman shape) adjacent to its substrate, in this case also a membrane‐bound protein, which can be cut (‘cleaved’) by the enzyme.

Figure 2.6 The nucleus.

Figure 2.7 The structure of DNA.

Figure 2.8 DNA replication.

Figure 2.9 Transcription.

Figure 2.10 Protein translation.

Figure 2.11 The endoplasmic reticulum and Golgi complex.

Figure 2.12 Endocytosis.

Figure 2.13 The cell cycle.

Figure 2.14 Phases of the cell cycle.

Figure 2.15 Control of apoptosis.

Chapter 03

Figure 3.1 Classification of epithelial tissues.

Figure 3.2 Haematoxylin‐ and eosin‐stained section of oral epithelium.

Figure 3.3 Histological section showing adipocytes embedded in loose connective tissue.

Figure 3.4 Histological section through the periodontium showing the collagen fibres of the periodontal ligament.

Figure 3.5 Histological section taken from the trachea showing part of the C‐shaped hyaline cartilage ring.

Figure 3.6 Histological section showing the structure of fibrocartilage.

Figure 3.7 Histological section through the growth plate of a 5‐week‐old rat.

Figure 3.8 Longitudinal section through a femur to show the cortical and trabecular bone.

Figure 3.9 (a) Image of a ground section of mineralized cortical bone. The ‘tree‐ring’‐like structures that arise are called Haversian systems. (b) Ground section image of mineralized trabecular bone.

Figure 3.10 Histological section of demineralized woven bone formed by endochondral ossification. The blue‐coloured regions are remaining areas of hypertrophic cartilage which are being remodelled into woven bone.

Figure 3.11 Appearance and structure of skeletal muscle.

Figure 3.12 Structure of muscle and the sliding filament theory.

Chapter 04

Figure 4.1 The structure of the heart.

Figure 4.2 Blood flow and electrical conduction pathways in the heart.

Figure 4.3 A typical electrocardiogram (ECG).

Figure 4.4 Bowditch, Treppe or Staircase effect.

Figure 4.5 Frank–Starling response.

Figure 4.6 Basic anatomy of the circulatory system.

Figure 4.7 Structure and function of the different blood vessels.

Figure 4.8 Mechanisms to redistribute blood flow.

Figure 4.9 Maintenance of a stable blood pressure.

Figure 4.10 Effect of posture on blood distribution.

Figure 4.11 Basic anatomy of the lungs.

Figure 4.12 Mechanics of expiration and inspiration.

Figure 4.13 Diffusion and partial pressures of gases.

Figure 4.14 Control of breathing rate.

Chapter 05

Figure 5.1 Somatic and autonomic nervous systems.

Figure 5.2 Spinal and cranial nerves.

Figure 5.3 Neuronal morphology.

Figure 5.4 (a) Neuronal cell membranes. (b) Membrane and action potential.

Figure 5.5 Generation of an action potential.

Figure 5.6 The synapse.

Figure 5.7 Effects of neurotransmitter binding on postsynaptic membrane potential.

Figure 5.8 Myelination. (a) Schwann cell myelinating axon of peripheral neurone. (b) Oligodendrocytes myelinating axons of central neurones. (c) Action potential conduction in myelinated and unmyelinated axons.

Figure 5.9 Immunofluorescent detection of astrocytes (shown coloured red).

Figure 5.10 The structure of peripheral nerves.

Figure 5.11 Dorsal and ventral roots, dorsal root ganglion and the trigeminal ganglion.

Figure 5.12 The spinal cord.

Figure 5.13 Signal transmission from CNS to periphery.

Figure 5.14 The autonomic nervous system.

Figure 5.15 The sympathetic and parasympathetic nervous systems.

Figure 5.16 (a) Anatomy of the brain. (b) MRI normal T1 sagittal section scan of the human brain.

Figure 5.17 Anatomy of the hindbrain.

Figure 5.18 Anatomy of the midbrain.

Figure 5.19 The forebrain. (a) Brodmann’s areas. (b) Motor and sensory regions of the cerebral cortex. (c) Somatotopic map showing the areas of the body laid out on the sensory and motor cortices.

Figure 5.20 Sensory pathways.

Figure 5.21 Motor pathways.

Chapter 06

Figure 6.1 Activation and function of the human complement system. The complement system is activated by the recognition of protein and carbohydrate antigens on pathogen surfaces (often interacting with antibody molecules) and comprises a series of interacting pro‐enzymes (zymogens) that form a proteolytic cascade of activation leading to the localized production of a limited number of effector molecules which attempt to eliminate the pathogen. Cleavage of the complement component C3 by activation of the enzyme C3 convertase is the common endpoint for all three activation pathways. The products of this reaction (C3a and C3b) are key complement effector molecules. C3b also activates C5 convertase which cleaves C5, producing further effector molecules (C5a and C5b). Complement effector pathways comprise binding to antigen to enhance neutrophil phagocytosis (opsonization), stimulating movement (chemotaxis) of neutrophils into sites of tissue inflammation and formation of a membrane attack complex which punctures the bacterial cell membrane, causing lysis.

Figure 6.2 Structure of a typical antibody molecule. Antibodies are the soluble form of immunoglobulin (Ig) molecules and are large proteins with a complex 3D (globular) structure. The F

ab

(antigen‐binding fragment) of different Ig molecules has a highly variable (clonal specific) amino acid sequence. The F

c

(crystallizable fragment) has a limited variability and functions to bind to F

c

receptors on phagocytes and NK cells. These fragments are joined by a flexible hinge region. The precise region of F

ab

which binds antigen (A) is formed by the combination of variable region peptides on the heavy and light chains of the Ig molecule. The heavy and light chains have contiguous non‐variable regions (constant regions) which are joined together by disulphide bonds. The constant heavy chain peptide forms the F

c

region of the Ig molecule and defines the antibody class (Table 6.6). T‐cell receptors (the antigen‐specific receptors on T‐cells; TCRs) have a similar globular structure and subunit composition (comprising TCRα and TCRβ chains or TCRγ or TCRδ chains).

Figure 6.3 Structure and recombination of Ig genes. The constant region of the Ig heavy chain is encoded by one of nine possible constant (C) genes in the genome depending on the class or subclass of antibody to be synthesizes. The variable region of the Ig heavy chain peptide (Figure 6.2) is encoded by a combination of three genes: one variable (V) gene, one diversity (D) gene and one joining (J) gene. The human genome has multiple variants of each of these genes, but only one of which contributes to Ig synthesis in each individual B‐cell clone; the possible combinatorial variations of Ig heavy chain variable region genes contribute to potential diversity of antigen‐binding sites on Ig molecules. DNA containing the specific combination of VDJC genes necessary for Ig synthesis is produced as the result of a somatic recombination process that takes place in maturing B‐cells. The Ig heavy chain peptide is combined with Ig light chain peptide (produced via a similar process) in immature B‐cells to produce the Ig molecule ready for export. T‐cell receptors are synthesized in developing T‐cells by analogous processes.

Figure 6.4 Activation of antigen‐specific T‐cells by antigen‐presenting cells. T‐cell receptors on naïve T‐cells recognize fragments of macromolecules produced as the result of ‘processing’ and ‘presentation’ in the context of MHC molecules in APCs such as dendritic cells. Other important connections take place at the surface of T‐cells and APCs. Thus, the CD4 molecule on one T‐cell subset (CD4+ T‐cells) serves to cooperate with TCRs in their interaction with MHC class II molecules on APCs (signal 1). Conversely, CD8+ T‐cells (which do not express CD4) interact exclusively with MHC class I molecules (not shown). The intercellular binding of so‐called co‐receptors such as B7.1 or B7.2 on APCs with CD28 on T‐cells (signal 2) is required in the initial stages of infection where naïve T‐cells, which have never encountered their cognate antigen before, are activated (for example, in a lymph node). Subsequent encounter with antigen/MHC molecules on target cells at the site of infection does not require this secondary signal. Activation of T‐cells also requires cytokines such as IL‐6, IL‐12 and TGF‐β derived from the APC (signal 3); the precise combination of cytokines influences T‐cell differentiation and therefore the effector phenotype of the T‐cell (see Table 6.8).

Figure 6.5 Holistic scheme illustrating the immune response to infection. Illustration of the dynamic of the host response to infection with a microbial pathogen. The immune system has several layers of effector mechanism which integrate to achieve destruction and/or elimination of pathogenic microorganisms. These are often categorized into innate and adaptive immunity although this is not always useful as these elements are highly integrated and mutually dependent. The exact nature of the host response and the stage at which the infection is halted is dependent on the site of infection, the exposure and the nature of the pathogen itself. Understanding the diverse elements of the immune response and their interaction is critical to the development of prophylactic measures (e.g. vaccines, allergen avoidance), therapies (anti‐inflammatory and immunosuppressive drugs) and novel approaches to clinical management (biomarkers).

Chapter 07

Figure 7.1 Micrographs of important oral bacteria. (a)

Streptococcus gordonii

, (b)

Actinomyces naeslundii

, (c)

Fusobacterium nucleatum

, (d)

Treponema denticola

.

Figure 7.2 Cervicofacial actinomycosis.

Figure 7.3 Gram stain of

Candida albicans

showing filamentous growth (true hyphae and pseudohyphae) arising from mother cells (blastospores).

Figure 7.4 Spatiotemporal model of plaque accretion. Primary colonizers associate with components of the acquired pellicle on the tooth surface and with each other via coadhesion/coaggregation. This generates a substratum with which incoming secondary colonizers can then associate. As the plaque matures, production of extracellular polymeric substance provides structural integrity and a conduit for the exchange of molecules. Nutritional adaptation, intermicrobial signalling (yellow stars) and beneficial/antagonistic interactions lead to the formation of distinct microbial societies within the plaque community that provide optimal metabolic networks and protection. Ultimately a climax community is formed that, in times of health, exists in equilibrium with its host.

Figure 7.5 Cariogenic attributes of

S. mutans

. Antigen I/II polypeptides promote attachment to gp340 within the acquired pellicle on the tooth surface, while glucosyltransferases (GTFs) synthesize glucans from fermentable carbohydrate. Glucans in turn are bound by glucan‐binding proteins (GBPs), providing additional structural stability to the plaque biofilm. Glucans, together with intracellular polysaccharide stores, can be broken down via glycolysis to yield energy, with lactic acid released as a waste product. This causes a drop in pH in the local environment. If this reaches pH 5.5 or lower, demineralization of the tooth surface occurs, leading to formation of a carious lesion.

Figure 7.6 Effects of periodontitis. Healthy periodontal tissue (left) contains connective tissue and alveolar bone, which support the tooth root. In addition, the oral epithelium covers this supporting tissue, and a specialized junctional epithelium connects it to the tooth surface. The space between the epithelial surface and the tooth is named the sulcus and is filled with gingival crevicular fluid. In cases of periodontitis (right), a dental plaque biofilm accumulates on the surface of the tooth and tooth root and causes the destruction of periodontal connective tissue and alveolar bone.

Figure 7.7 Radiograph showing dry socket (arrow), 3 months post‐extraction.

Figure 7.8

Candida

‐associated denture stomatitis.

Figure 7.9 Angular cheilitis.

Figure 7.10 Herpes labialis (cold sore) caused by reactivation of HSV‐1.

Figure 7.11 Burkitt’s lymphoma caused by EBV.

Figure 7.12 Hand, foot and mouth disease. Arrow indicates tongue lesion.

Figure 7.13 Verruca vulgaris (wart) caused by human papillomavirus.

Chapter 08

Figure 8.1 Cell responses to injury.

Figure 8.2 Nuclear changes in cellular necrosis.

Figure 8.3 Types of necrosis.

Figure 8.4 Mechanism of neoplastic transformation.

Figure 8.5 Vascular events.

Figure 8.6 Explanation of vascular events: vasodilation.

Figure 8.7 Formation of oedema.

Figure 8.8 White cell distribution in the vessels of normal tissue. In normal blood flow, white and red blood cells are present in the centre of the vessel surrounded by the liquid part of the blood.

Figure 8.9 White cell distribution in inflammation. (1) In inflammation the white blood cells move to the edges of the vessel. This is called margination and is due to vascular stasis. (2) They then adhere to the endothelial cells. This is known as pavementation. (3) White blood cells emigrate between endothelial cells and into the tissues, attracted by chemokines.

Figure 8.10 Histological appearance of pus: dense accumulations of neutrophils which have multilobed nuclei (arrows). Macrophages are larger and engulf necrotic tissue and dead neutrophils (*).

Figure 8.11 Histological section of granulation tissue from a healing wound. Fibroblasts are indicated by arrows and endothelial cells lining the blood vessels by arrowheads. The large round cells containing brown pigment are macrophages which have engulfed red blood cells.

Figure 8.12 Maturation of granulation tissue. (a) Fibroblasts lay down collagen (arrow) and the tissue becomes less cellular and vascular. (b) Scar tissue composed of dense collagen may form.

Figure 8.13 Activation of macrophages.

Figure 8.14 Activation of lymphocytes.

Figure 8.15 Granulomatous inflammation.

Figure 8.16 Tuberculosis.

Chapter 09

Figure 9.1 The foremen of the skull.

Figure 9.2 The face.

Figure 9.3 (a) The TMJ and (b) muscles of mastication.

Figure 9.4 Sensory innervation of the oral cavity.

Figure 9.5 The orbit.

Figure 9.6 Schematic of eye with muscles.

Chapter 10

Figure 10.1 (a) The primitive oral cavity, the stomatodeum, with the ectomesenchyme (EM) lying beneath a lining of epithelium (arrows) and (b) the primary epithelial band (arrow).

Figure 10.2 The bud stage of tooth development. The bud is formed from the invading epithelium and concurrent condensation of surrounding ectomesenchymal cells.

Figure 10.3 The dental follicle (DF) surrounds the enamel organ and limits the dental papilla. It is this structure that is responsible for formation of the supporting structures of the tooth.

Figure 10.4 The enamel undergoes specific cellular changes in preparation for secretory function and four distinct cell layers are formed in this part of the tooth germ due to cellular proliferation and histo‐differentiation. These four cell layers are the inner enamel epithelium (IEE), outer enamel epithelium (OEE), the stellate reticulum (SR) and the stratum intermedium (SI), which is a two‐ to three‐cell‐layer‐thick area lying next to the inner enamel epithelium.

Chapter 11

Figure 11.1 Fates of Meckel’s cartilage. Meckel’s cartilage at the symphysis remains as persistent cartilage (blue). The main body of Meckel’s disappears during embryonic development (yellow). The most proximal part undergoes ossification and forms two of the three middle ear bones (red). The part between the lower jaw and middle ear transforms into the sphenomandibular ligament (green). Forming dentary bone in orange.

Figure 11.2 Jaw articulation in mammals and non‐mammals. A comparison of the jaw articulation. Mammal on left, bird on right. The homologous skeletal elements are shown in the same colour to illustrate the shift in function, position and size of these elements during evolution.

Figure 11.3 Schematic of the human skull showing the processes of the mandible (dentary bone) and its connection to the rest of the skull.

Figure 11.4 Schematic of the TMJ showing the position of the disc at the junction of the upper and lower jaw.

Figure 11.5 Skull vault: sutures. Sagittal (left) and anterior (right) views of the skull of a newborn outlining the sutures and fontanelles that separate the skull bones.

Figure 11.6 Tongue structure. Schematic showing the layout of taste buds, their embryonic origin and their innervation across the tongue.

Figure 11.7 Diagram of a taste bud showing the contribution of different receptor cells, basal and support cells to the bud.

Figure 11.8 Palate development and clefts. Virtual frontal sections through a human embryonic head. Left‐hand side: normal palate development. The shelves on either side of the tongue rise up, grow together and then meet in the midline. Once they have met in the midline the epithelial seam is lost to form a continuous palate separating the oral and nasal cavities. Right‐hand side: defects associated with palate development. Either one or both of the shelves can fail to rise. The shelves can rise but not grow together or the shelves can meet but the midline epithelial seam remains, leading to a submucosal cleft.

Figure 11.9 Primary tooth formation in cleft lip patients. Schematic showing the layout of developing tooth germs across the upper jaw with the placode (a thickening of the epithelium) for the lateral incisor forming at the fusion point between the maxillary and medial nasal processes. A cleft in this region splits the tooth placode leading to either loss of the tooth or the formation of supernumerary lateral incisors.

Chapter 12

Figure 12.1 Sources of salivary biomarkers. Salivary fluid is primarily derived from salivary gland secretion. Most of the protein content of saliva is due to salivary proteins synthesized and secreted by salivary acinar cells. However, saliva in the mouth also contains epithelial cells shed from the mucosal surfaces, blood cells (neutrophils) from gingivae and oral microorganisms, mainly species of bacteria. Small amounts of blood and tissue fluid proteins enter saliva mainly from the gingivae. GCF, gingival crevicular fluid.

Figure 12.2 Ductal systems and positions of major salivary glands. Injection of radio‐opaque contrast medium into the main ducts of salivary glands enables imaging of the ductal systems. (a) Positive image of the contrast medium in the parotid gland. (b) Negative image of the contrast medium in the submandibular gland. The opening of the main parotid duct at the level of the upper molars is clearly seen (arrows).

Figure 12.3 Histological appearance of salivary gland cells revealed by microscopy. The acinar cells of salivary glands have an appearance that depends upon the proteins and glycoproteins stored in granules in the cytoplasm. (a) Acinar cells of parotid glands stain darkly with H&E. (b) Minor mucus gland acinar cells contain abundant mucin‐containing storage granules that do not stain with H&E. (c) When mucin‐containing cells are stained with periodic acid–Schiff (PAS) reagent and Alcian blue, mucins stain dark blue. In this panel the staining reveals that submandibular glands have some mucin‐containing and many non‐mucin‐containing acini. (d) Sublingual gland acinar cells, mostly mucin‐containing; all are stained dark blue with Alcian blue. (Note: the images in a–d are taken at different magnifications.) (e) Myoepithelial cells are supporting cells that ‘wrap around’ the outside of acini and small ducts as revealed by fluorescent staining in this three‐dimensional image. (f) The apical membrane of acinar cells is different from the basolateral membrane and contains the membrane‐bound water‐transporting protein aquaporin 5 as shown by the fluorescent staining in this three‐dimensional image.

Figure 12.4 Control of salivary secretion by nerves. The salivary reflex begins with the detection of food and tastants such as acid and salt by taste buds and mechanoreceptors on the tongue; in addition the chewing of food is detected by mechanoreceptors in the periodontal ligament around teeth. Signals in afferent sensory nerves (green) are relayed to the salivary centres from where efferent parasympathetic nerves conduct signals to the salivary glands (blue). Sympathetic efferent nerves (red) arise from the thoracic spinal cord. Nerves within the CNS (black) innervate the salivary centres and influence nerve‐mediated signals to the salivary glands.

Figure 12.5 Intracellular coupling of salivary secretion in acinar cells. Fluid secretion is dependent mainly upon activation of muscarinic M3 receptors by acetylcholine released from parasympathetic nerves. The intracellular coupling mechanism is characterized by an elevation of calcium released from the endoplasmic reticulum (ER) and activation of chloride release. Protein secretion is mainly activated by release of noradrenaline by sympathetic nerves and activation β

1

‐adrenoceptors; vasointestinal peptide released from parasympathetic nerves binds to vasointestinal polypeptide (VIP) receptors. Intracellular signalling is characterized by an increase in cyclic AMP (cAMP), which activates protein kinase A leading to exocytosis of protein storage granules and release of protein into saliva. Gq and Gs, G proteins; PLC, phospholipase C; PIP

2

, phosphatidylinositol biphosphate; IP

3

– inositol triphosphate; IP

3

R, IP

3

receptor; AdC, adenylate cyclase; PKA, protein kinase A.

Figure 12.6 Secretion of components of saliva and modification of composition by ducts. Saliva secretion is dependent upon the low intracellular sodium concentration created by the active sodium pump (ATP). Saliva secretion begins with the movement of sodium and chloride into the acinar lumen; water follows due to the osmotic gradient of salt and enters the acinar lumen by moving between cells or through the water channel (W), aquaporin 5, present in the apical membrane. Different ion transport membranes in the acinar cell membranes allow the salt and water movement: a chloride channel in the apical membrane is opened on glandular stimulation; sodium follows, travelling between acinar cells through leaky tight junctions (TJL). Chloride enters acinar cells through a chloride co‐transporting protein in the basolateral membrane which utilizes the concentration gradient of low intracellular sodium to drive chloride into the cell. Saliva secreted by acinar cells is isotonic. Ductal cells remove sodium and chloride due to the presence of membrane transporter proteins and the low intracellular sodium concentration created by the sodium pump. The tight junctions (TJ) between ductal cells are not leaky and do not allow the movement of water; also there is no water channel in ductal cells. Ductal cells can secrete bicarbonate (HCO

3

−

). Following modification by ducts, saliva becomes hypotonic.

Figure 12.7 Saliva on surfaces of the mouth. Saliva forms a fluid layer or film over all of the surfaces of the mouth and the film thickness depends upon the surface. The enamel surfaces of teeth have a thin fluid film of less than 5 µm while the anterior tongue has a film thickness of approximately 70 µm. Underneath the fluid layer are protein pellicles, adsorbed (bound) layers of salivary proteins and mucin which have a thickness of approximately 50 nm. All of these layers are important in providing salivary function in the mouth. The adsorption of the lubricating/hydrating mucin layer is dependent upon adsorption of other salivary proteins to the surfaces of epithelial cells and teeth. The layer is protective and renewable.

Chapter 13

Figure 13.1 The volume/temperature diagram for a glass‐forming liquid. Letters are referred to in the text.

Figure 13.2 Schematic two‐dimensional representation of the structure of silica SiO

2

in its (a) crystalline and (b) vitreous forms.

Figure 13.3 Schematic two‐dimensional representation of the structure of mixed‐oxide glass.

Figure 13.4 Examples of different monomers that are used to create polymeric materials used in dentistry (a) glycerol methacrylate and (b) methyl methcrylate.

Figure 13.5 Stress/strain curve of a ductile material showing the elastic (Young’s) modulus (

E

) given by the gradient of the linear region. Also shown are yield stress (σ

y

), ultimate strength (σ

u

) and fracture stress (σ

f

). The area under the curve in the linear, elastic region is the resilience and that under the whole curve is the material’s toughness.

Figure 13.6 Shade guide for assessment of tooth colour and selection of appropriate dental material.

Guide

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Basic Sciences for Dental Students

Edited by Simon A. Whawell and Daniel W. Lambert

School of Clinical Dentistry,University of Sheffield,Sheffield, UK

This edition first published 2018© 2018 John Wiley & Sons Ltd

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Library of Congress Cataloging‐in‐Publication Data

Names: Whawell, Simon A., 1965– editor. | Lambert, Daniel W., 1976– editor.Title: Basic sciences for dental students / edited by Simon A. Whawell, Daniel W. Lambert.Description: First edition. | Hoboken, NJ : Wiley, 2018. | Includes bibliographical references and index. |Identifiers: LCCN 2017033954 (print) | LCCN 2017035293 (ebook) | ISBN 9781118906095 (pdf) | ISBN 9781118906088 (epub) | ISBN 9781118905579 (pbk.)Subjects: | MESH: Dentistry–methods | Biological Science Disciplines | Dental CareClassification: LCC RK76 (ebook) | LCC RK76 (print) | NLM WU 100 | DDC 617.60071/1–dc23LC record available at https://lccn.loc.gov/2017033954

Cover Design: WileyCover Image: Courtesy of Heather Wallis

List of Contributors

Fiona M. BoissonadeSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Aileen CrawfordSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Paula M. FarthingSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Paul V. HattonSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Stuart HuntSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Peter P. JonesOtago School of Medical Sciences, University of Otago, Dunedin, New Zealand

Daniel W. LambertSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Cheryl A. MillerSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

Angela H. NobbsBristol Dental School, University of Bristol, Bristol, UK

Gordon B. ProctorKing’s College London Dental Institute, London, UK

Alistair J. SloanSchool of Dentistry, University of Cardiff, Cardiff, UK

John J. TaylorSchool of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK

Abigail S. TuckerDepartment of Craniofacial Development and Stem Cell Biology, King’s College London, London, UK

Simon A. WhawellSchool of Clinical Dentistry, University of Sheffield, Sheffield, UK

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1Biomolecules

Daniel W. Lambert and Simon A. Whawell

School of Clinical Dentistry, University of Sheffield, Sheffield, UK

Learning Objectives

To understand the basis of molecular structure and bonding.

To outline the basic structure and function of proteins, carbohydrates, lipids and nucleic acids.

To be able to describe the biological role of enzymes and explain how their activity is regulated.

To understand basic energy‐yielding pathways and how they are controlled.

Clinical Relevance

An understanding of basic biomolecule structure and function provides a foundation for all normal cell and tissue structure and physiology. The structure of biomolecules present in the human body closely relates to their function, as is the case for cells and tissues. In disease, drugs can be used that target specific biochemical pathways, so an appreciation of biochemistry underlies patient care as well as the diagnosis, prognosis and treatment of disease.

Introduction

As complex as the human body is, it is heavily dependent on just four atoms for its composition: carbon, hydrogen, nitrogen and oxygen. These atoms form structurally diverse groups of biologically important molecules, their structure always relating to their function in the same way that the cells and tissues of the body are adapted. Biomolecules commonly take part in relatively simple reactions which are subject to complex control to finely tune the essential processes that they mediate. Biomolecules are often large polymers made up from smaller molecular monomers and even though there are thousands of molecules in a cell there are relatively few major biomolecule classes. Fatty acids, monosaccharides, amino acids and nucleotides form di‐ and triglycerides, polysaccharides, proteins and nucleic acids respectively. Small molecules are also important to biology, as we will see; adenosine triphosphate (ATP), for example, stores energy for catabolic and anabolic process and nicotinamide adenine dinucleotide (NADH) is the principle electron donor in the respiratory electron transport chain.

Biological Bonding

Molecular bonds are dependent on the arrangement of electrons in the outermost shell of each atom, being most stable when this is full. This can be achieved by transferring electrons, which takes place in ionic bonding (e.g. NaCl) or by sharing electrons in a covalent bond. Biological systems are also crucially dependent on non‐covalent bonds, namely hydrogen bonds (or H bonds), electrostatic interactions and van der Waals’ forces. While these ‘bonds’ are associated with at least an order of magnitude lower energy than covalent bonds they are collectively strong and can have significant influence on biological reactions. Non‐covalent bonds differ in their geometry, strength and specificity. Hydrogen bonds are the strongest and form when hydrogen that is covalently linked to an electronegative atom such as oxygen or nitrogen has an attractive interaction with another electronegative atom. They are highly directional and are strongest when the atoms involved are co‐linear. Hydrogen bonds are important in the stabilization of biomolecules such as DNA and in the secondary structure of proteins. Charged groups within biomolecules can be electrostatically attracted to each other. Amino acids, as we will discuss later, can be charged and such electrostatic interactions are important in enzyme–substrate interactions. The presence of competing charged ions such as those in salt would weaken such interactions. Finally, the weakest of the non‐covalent interactions is the non‐specific attraction called the van der Waals’ force. This results from transient asymmetry of charge distribution around a molecule which, by encouraging such asymmetry in surrounding molecules, results in an attractive interaction. Such forces only come into play when molecules are in close proximity and although weak can be of significance when a number of them form simultaneously.

Water, Water Everywhere

The human body is of course comprised mostly of water but it is worth mentioning the profound effects that water has on biological interactions. Two properties of water are particularly important in this regard, namely its polar nature and cohesion. A water molecule has a triangular shape and the polarity comes from the partial positive charge exhibited by the hydrogen atom and the partial negative charge of the oxygen. The cohesive properties of water are due to the presence of hydrogen bonding (Figure 1.1). Water is an excellent solvent for polar molecules and does this by weakening/competing for hydrogen bonds and electrostatic interactions. In biology, water‐free microenvironments must be created for polar interactions to have maximum strength.

Figure 1.1 The chemical structure of water.

Amino Acids and Proteins

Proteins are polymers of amino acids and are the most abundant and structurally and functionally diverse group of biomolecules. They form structural elements within the cell and extracellular matrix, act as transport and signalling molecules, interact to enable muscles to contract and form the biological catalysts (enzymes) without which most cell functions would cease. Amino acids consist of a tetrahedral alpha C atom (Cα) attached to a hydrogen atom, amine and carboxyl groups and a substituted side group (R) (Figure 1.2a), which can be anything from a hydrogen atom to a more complicated structure. Amino acids are chiral and in biology all are the left‐handed (L) isomers. Many possible amino acid structures exist but only 20 occur naturally and are used for protein synthesis. Some of these are synthesized in the body from other precursors and some amino acids have to come from our diet (called essential amino acids). Amino acids can be broken down to form glucose as an energy source and can also act as precursors for other molecules such as neurotransmitters.

Figure 1.2 (a) Peptide bond and (b) amino acid ionization.

Urea Cycle

Amino acids cannot be stored or secreted directly so must be broken down prior to their removal from the body. Their carbon skeletons may be converted to glucose (glucogenic amino acids) or acetyl‐CoA or acetoacetate (ketogenic), which can be fed into the tricarboxylic acid (TCA) cycle, generating energy. The nitrogen is then removed in three steps starting with transfer of the amino group (transamination) to glutamate which is then converted to ammonia by glutamate dehydrogenase in the liver. Finally ammonia enters the urea cycle, a series of five main biochemical reactions that results in the formation of urea, which is excreted in urine. The urea cycle is a good example of a disposal system where ‘feed‐forward’ regulation through allosteric activation of the enzymes involved results in a higher rate of urea production if there is a higher rate of ammonia production (see Allosterism later in this chapter). This is important given that ammonia is toxic and also explains why a high‐protein diet and fasting, which results in protein breakdown, induce urea cycle enzymes.

Amino Acid Ionization

The amide and carboxyl groups and some side chains of amino acids are ionizable and their state is dependent on the pH (Figure 1.2b). If you were to titrate an amino acid, at low pH all groups are protonated, the amino group carries a positive charge and the carboxyl group is uncharged. As the pH increases the proton dissociates from the carboxyl group, half being in this form at the first pK value of around pH 2 (pK1 on Figure 1.2b). As the pH increases further the amino acid is zwitterionic with both positive and negatively charged groups. As the net charge is zero this is the isolelectric point of an amino acid (pI on Figure 1.2b). At the second pK of pH 9 (pK2 on Figure 1.2b) half of the amine groups carry charge and the overall charge is negative. Titration curves for amino acids are not linear around the pK values as there is resistance to changes in pH as the amino acids act as weak buffers. If there is an ionizable side chain present there would be a third pK value; acidic amino acids lose a proton at pH 4 and thus have a negative charge at neutral pH. For basic amino acids this occurs around pH 10 and thus such amino acids are positively charged at neutral pH.

Classification of Amino Acids

As the only difference between amino acids is the nature of the substituted side chain this determines the characteristics of the amino acid, such as the shape, size, charge, chemical reactivity and hydrogen bonding capability. This ultimately determines the structure and function of the protein polymer that the amino acids form. Amino acids can be classified according to their structure or chemical nature; the latter is summarized in Figure 1.3. Polar amino acids have uneven charge distribution even though they have no overall charge. The hydroxyl and amide groups are capable of hydrogen bonding with water or each other and thus these amino acids are hydrophilic and often found on the surface of water‐soluble globular proteins. Cysteine is often included in this group and is very important in protein structure as it can from covalent disulphide bonds with other amino acids in the protein polymer. Tyrosine is an aromatic amino acid containing a six‐carbon phenyl ring but as this contains a hydroxyl group capable of hydrogen bonding it is polar. Non‐polar amino acids have side chains with evenly distributed electrons and therefore do not form hydrogen bonds. They tend to form hydrophobic cores within proteins. Phenylalanine and tryptophan are aromatic and methionine contains sulphur. Aspartate and glutamate have carboxylic groups that carry a negative charge at neutral pH, which is why they are referred to as ‘‐ate’ and not acid. Their presence in a protein would impart a negative charge that would allow electrostatic interactions to take place. Three amino acids carry a positive charge at neutral pH and these are highly hydrophilic. Lysine and arginine are always charged at biological pH, but histidine has a pK close to neutral pH and thus its charge is dependent on the local environment. It is this feature that gives this amino acid an important role in the active site of enzymes.

Figure 1.3 Classification of amino acids. Note that amino acids can be referred to using one‐ or three‐letter codes. This figure uses the former; so C represents cysteine, which in the three‐letter code would be Cys. SH is the thiol group of cysteine that can react to form a disulphide bridge (represented elsewhere by S–S) with another cysteine residue.

Peptide Bonding

Amino acids form protein polymers through a condensation reaction resulting in the formation of a peptide bond between the carboxyl group of one amino acid and the amine group of another (Figure 1.2a). The sequence of amino acids in the resultant protein is determined by the genetic code of the messenger RNA (mRNA) with the average protein having approximately 300 amino acids. The peptide bond is rigid and the atoms are in the same geometric plane; there is, however, considerable flexibility around the bond which has a significant effect on protein structure. Peptide bonds are very stable and are only physiologically broken by proteolytic enzymes.

Protein Structure

Whether they are globular, fibrous or span the cell membrane, proteins take part in highly specific interactions the nature of which is intimately associated with the conformation and shape of the protein. The structure provides binding sites for these specific interactions and determines the flexibility, solubility and stability of the protein (Feature box 1.1). Protein structure is influenced by the amino acid sequence and character of the side chains in particular. Cysteine, as we have mentioned previously, carries out a special role in the formation of disulphide linkages and hydrogen bonding is very important in protein structure. Water influences shape as proteins will naturally fold with hydrophilic residues exposed to the aqueous environment and hydrophobic residues hidden away inside the protein. Chaperones are barrel‐shaped proteins that also assist in the folding of some proteins and by overcoming kinetic barriers to folding and providing a water‐free micro‐environment and template. The structure of proteins is often divided into the following levels: the primary structure refers to the linear sequence of amino acids, the secondary structure relates to how this sequence is formed into regular structures such as helices or sheets and the tertiary structure is how the secondary structure is folded in three dimensions (Figure 1.4). Finally some proteins have a quaternary structure which is the spatial arrangement of individual polypeptide subunits.

Figure 1.4 Three‐dimensional structure of salivary amylase.

Feature box 1.1 Protein folding and disease

A diverse number of degenerative diseases have a common feature that protein misfolding leads to accumulation of deposits within the brain. These so‐called amyloid diseases include Alzheimer’s, Huntingdon’s and Parkinson’s diseases and are characterized by the formation of tightly packed β‐pleated sheets that are highly resistant to degradation. In a similar way prion disease such as Creutzfeldt–Jakob disease (CJD) and bovine spongiform encephalopathy (BSE) induce protein misfolding by templating. Such agents are of particular importance for clinical students as prions cannot be destroyed by traditional sterilization procedures.

Posttranslational Modifications

Additions are commonly made to amino acids after they have been formed into proteins which can significantly change their properties. Glycosylation is the addition of carbohydrate and acts as a ‘tag’. Phosphorylation is the addition of phosphate to serine, tyrosine and threonine which by adding a significant negative charge changes the local structure of the protein allowing it to be recognized by other molecules. Intracellular signalling pathways are often cascades of phosphorylation reactions controlled by kinase enzymes that add phosphate and phosphatase enzymes that remove it. (See Other Regulatory Mechanisms later in this chapter.)

Enzymes

Enzymes are proteins that catalyse biological reactions; that is, they speed them up without themselves being permanently altered. They also regulate many of the biochemical pathways in which they play a role (see Control of Metabolism in this chapter). Enzymes bind substrates in their active sites and convert them into products. The substrates are bound to specific regions in the active site: these are the functional groups(in basic terms this means bits of the molecules which can have electrostatic interactions with the substrate) of the amino acids making up the substrate‐binding site, or those of coenzymes and metal ions. This specificity of binding makes enzymes extremely selective for their substrates. In the course of any reaction, a transition‐state complex is formed. This is an intermediate with the highest energy of any component of the reaction: the energy needed to overcome this to form the products is called the activation energy. Enzymes reduce the activation energy by stabilizing the complex, and thereby increase the rate of the reaction (Figure 1.5). This specificity can be exploited by drugs and toxins which potently and selectively inhibit enzymes. These can be covalent inhibitors, which form covalent bonds with functional groups in the active site, or transition‐state analogues, which mimic the transition‐state complex (Feature box 1.2).

Figure 1.5 Enzyme–substrate complexes and the transition state.

Feature box 1.2 Penicillin, a transition‐state analogue

Penicillin is a widely used antibiotic, derived from the fungus Penicillum. The discovery of penicillin’s antimicrobial properties is widely credited to the observation in 1925 by Alexander Fleming that contamination by Penicillum of culture plates on which a bacterium, Staphylococcus, was being grown, inhited the growth of the bacteria. Penicillin was subsequently isolated from the fungus and has been used to treat a wide range of infections for decades, although bacterial resistance to the drug is now widespread. Penicillin is effective as it inhibits a transpeptidase enzyme required to form bacterial cell walls, causing the bacteria to ‘burst’. Penicillin inhibits the enzyme as it tightly binds to the transition‐state complex formed during the transpeptidase‐catalysed reaction, preventing the formation of products.

Regulation of Enzyme Activity

pH and Temperature

The binding of substrate to the active site is determined by electrostatic interactions. Changes in pH alter the properties of functional groups within the active site and therefore change the interactions. Enzymes are hence very sensitive to pH, with different enzymes having different optimum pH values according to their function. As they are proteins with complex tertiary structures, enzymes are also sensitive to temperature. Basic thermodynamic principles dictate that the speed of the reactions will increase with temperature owing to increased substrate energy and probability of collisions, but in an enzyme‐catalysed reaction this only occurs up to the point at which the temperature begins to break bonds within the enzyme; even small changes in the shape of the enzyme can interfere with substrate binding. Most enzymes function best below 40 °C; however, some organisms living in deep‐sea vents have enzymes that function at 95°C! (See Feature box 1.3.)

Feature box 1.3 A molecular revolution from hot springs

In the 1960s scientists were investigating whether bacteria could survive at high temperatures, in environments such as hot springs. They identified a species, Thermus aquaticus, which was found thriving at temperatures of 70°C in the geysers of Yellowstone National Park. The researchers quickly realized that to survive at this temperature the bacterium must have evolved enzymes that could function at temperatures that would denature most proteins. Later, the DNA polymerase enzyme catalysing replication of the bacterial DNA was isolated and developed for use in the polymerase chain reaction (PCR), a method now used in thousands of laboratories worldwide to amplify short sections of DNA.

Substrate

The rate of all enzyme reactions is dependent on substrate concentration; they show saturation kinetics, with rate of reaction increasing with increasing substrate concentration (or [S]) until saturation, when maximum velocity (Vmax) is reached. The relationship between substrate concentration and reaction velocity is described by the Michaelis–Menton equation:

This equation is useful because the Michaelis constant (Km) is a measure of the affinity an enzyme has for its substrate, and together with Vmax can be used to determine the nature of a particular inhibitor, which may act in a competitive, non‐competitive or uncompetitive manner (Figure 1.6).

Figure 1.6 Mechanisms of enzyme inhibition. (a) Competitive inhibition. (b) Non‐competitive inhibition.

Allosterism

Many enzymes are allosteric; that is, they are inhibited or activated by molecules binding to them at a site other than the active site (Figure 1.7). This binding alters the shape of the active site by changing the overall shape of the enzyme. Allosteric inhibitors can be either homotrophic (the substrate itself binds to the enzyme somewhere other than its active site) or heterotrophic (a molecule other than the substrate binds to the enzyme away from its active site). Allosteric regulation is particularly important in the regulation of metabolic pathways, which are often regulated by the rate of one key enzyme. In many pathways, this enzyme is regulated (often allosterically) by the end product of the pathway (see Control of Metabolism).

Figure 1.7 Allosteric regulation of protein kinase A.

Other Regulatory Mechanisms

Enzymes can also be regulated in a variety of other ways. One of these is covalent modification, probably best illustrated by the addition of a phosphate group to an amino acid residue in the enzyme, which alters the shape of the active site. This phosphorylation is carried out by another enzyme called a kinase, and can be reversed by another type of enzyme, termed a phosphatase. It may sound a trifle unexciting but this is a big deal: virtually all cellular signalling processes are carried out by cascades of enzymes phosphorylating and dephosphorylating each other and defects in this are responsible for many diseases, particularly cancer. A closely related regulatory mechanism is through protein–protein interactions, which as you might surmise is alteration of enzymic activity caused by the binding of another protein. A calcium‐binding protein, calmodulin, is one of the proteins that do this and its importance is illustrated by the fact that it is present in large quantities in every type of cell and that it is evolutionarily ancient, being identical in nearly every species. Some enzymes are also regulated by being synthesized as an inactive ‘zymogen’, only becoming active when cut by another enzyme. This is often the case with proteases which would otherwise damage the cell in which they are synthesized.

Nucleic Acids

Deoxyribonucleic acid (DNA) contains all the information required to produce and maintain all the components of a cell. It comprises four bases – adenine (A), guanine (G), cytosine (C) and thymine (T) – each of which is bonded to a deoxyribose: each of these is termed a nucleoside. A nucleoside bound to a phosphate is termed a nucleotide, and nucleotides form a linear string along a phosphate backbone (Figure 1.8). It is the sequence of these four nucleotides that determines the sequence of every protein in the cell, which determines the function of the cell, which determines, ultimately, you. Two strands of nucleotides line up opposite each other, with each string going in the opposite direction; that is, one going 5′–3′ and one going 3′–5′ (termed antiparallel chains; Figure 1.9). The structure of the bases preferentially places adenine opposite thymine, and guanine opposite cytosine on the antiparallel chains; this allows the greatest number of bonds to form (other combinations are possible, but this is generally undesirable). The two strands are coiled into a helix (called a double helix as there are two strands). The majority of the DNA in a human cell is contained within the nucleus; this is covered in more detail in Chapter 2.

Figure 1.8 The structure of the four nucleotides of DNA.

Figure 1.9 Nucleotides form antiparallel chains.

The other major form in which nucleic acids are found in the cell is ribonucleic acid (RNA). RNA is also made up of chains of nucleosides, but in this case the base thymine is replaced by uracil. RNA does not form double‐stranded helices but is instead a single‐stranded molecule that can fold up on itself to form a wide array of structures. The sequence of RNA is copied from DNA by transcription (covered in more detail in Chapter 2), a process traditionally considered to produce three major types of RNA molecule – ribosomal RNA (rRNA), messenger RNA (mRNA) and transfer RNA (tRNA) – all of which play important roles in protein synthesis. In recent years, it has become apparent that many other forms of RNA exist, many of which have functions unrelated to protein synthesis (Feature box 1.4).

Feature box 1.4 Non‐coding RNA, the dark matter of the cell

Scientists have long been puzzled that a large proportion of the human genome, perhaps as much as 95%, does not encode known proteins. In recent years it has become apparent that much of this DNA is transcribed into various types of non‐coding RNA; collectively this is sometimes termed the ‘dark matter’ of the cell, as its function was until very recently largely unknown. Advances in RNA sequencing technology have now revealed that much of this RNA does appear to have an important functional role, and can be divided into many different classes of RNA, including lncRNA, miRNA and snoRNA. One of these lncRNAs, Xist, is critical in determining the sex of a developing embryo, and mutations in others have been found to occur in a number of diseases, but much is still not known of this uncharted RNA world.

Carbohydrates

The Structure of Carbohydrates

Carbohydrates are essential components of all living organisms and are the most abundant class of biological molecule. The basic carbohydrate unit is a monosaccharide. Monosaccharides are classified according to the chemical nature of their carbonyl group (the carbon in the aldehyde (aldoses) or ketone (ketoses) group) and the number of carbon atoms (e.g. hexose, 6C; heptose, 7C). The carbons in sugars with a ring structure are numbered in a clockwise manner, with the carbonyl carbon designated 1 (Figure 1.10). Monosaccharides form disaccharides by forming glycosidic linkages with other monosaccharides. Further linkages can be formed to form oligosaccharides and polysaccharides.

Figure 1.10 The structure of glucose.

Oligosaccharides and Polysaccharides