Biology. second edition. for the medical sciences. Philip Bradley & Jane Calvert

Transcription

1 Biology for the medical sciences Philip Bradley & Jane alvert second edition

2 ontents Preface Acknowledgements xi xii The molecules of life 1 Water and life The properties of water Water in the human body Test yourself 3 2 Proteins Introduction Primary structure Secondary structures Tertiary structure Quaternary structure Domains Functions of proteins onformational change Test yourself 12 3 arbohydrates Introduction Monosaccharides Glycosidic bond Polysaccharides Glycoconjugates Functions of carbohydrates Test yourself 18 4 Lipids Introduction Fatty acids Triglycerides and phospholipids holesterol Functions of lipids Test yourself 22 5 Nucleic acids and genes Introduction DNA and RNA DNA synthesis RNA synthesis The genetic code Protein synthesis 27

3 vi atch Up Biology 5.7 Introns and exons Regulation of gene expression Test yourself 31 ells and tissues 6 The cell Introduction Eukaryotic cells ell specialisation Test yourself 37 7 Microorganisms Introduction Bacteria Viruses Fungi ther infectious agents Treatment of infectious disease Test yourself 47 8 Energy metabolism Introduction The citric acid cycle Release of energy from fats and proteins xidative phosphorylation Anaerobic respiration Test yourself 53 9 Membrane transport Introduction smosis Facilitated diffusion Active transport Exocytosis and endocytosis Test yourself ell division and mitosis Introduction ell cycle ontrol of cell division ell division and differentiation Test yourself Reproduction Introduction Sexual reproduction Fertilisation Reproductive and therapeutic cloning Test yourself Inheritance Introduction 73

4 ontents vii 12.2 Definition of terms Mutations Mendelian inheritance Monohybrid inheritance Dihybrid inheritance Linkage Autosomal and sex-linked genes Genetic fingerprinting Evolution by natural selection Test yourself Genetic disease Introduction ystic fibrosis: an autosomal recessive disease untington disease: an autosomal dominant disease aemophilia A: an X-linked recessive disease Asthma: a disease caused by multiple genes Genetic testing Gene therapy and genetic diseases Test yourself Epithelial tissues Introduction lassification Adhesion Test yourself onnective tissues Introduction Glycosaminoglycans Fibres ells Test yourself Excitable tissues Introduction Membrane potential Muscle Nerve Test yourself 105 Systems 17 omeostasis Introduction Regulation of plasma glucose Thermoregulation Test yourself The endocrine system Introduction Types of hormone 114

5 viii atch Up Biology 18.3 ell signal receptors Second messenger systems Endocrine glands ypothalamo-pituitary axis Posterior pituitary ther endocrine glands Test yourself The nervous system Introduction Structure of nervous system The brain The spinal cord Peripheral nervous system Test yourself The cardiovascular system Introduction Blood Plasma Red blood cells Platelets The heart The circulatory system Test yourself The respiratory system Introduction Structure of the respiratory system Respiration Gaseous exchange ontrol of respiration Test yourself The digestive system Introduction ral cavity Structure of the GI tube The stomach Small intestine and accessory glands Large intestine Test yourself The reproductive system Introduction Male reproductive system Spermatogenesis Female reproductive system ogenesis and the menstrual cycle opulation and fertilisation Implantation and pregnancy Birth 158

6 ontents ix 23.9 Test yourself The urinary system The kidney The bladder Test yourself The immune system Immune responses to infection Inflammation Lymphocytes and the specific immune response Diseases of the immune system Test yourself The musculoskeletal system Introduction Bone Regulation of calcium levels artilage The skeleton Synovial joints Muscles and locomotion Test yourself 174 Answers to test yourself questions 175 Glossary 179 Index 203

7 03 arbohydrates Basic concepts: arbohydrates range in structure from simple sugar molecules, such as glucose, to polymers of sugar molecules, such as those that constitute the rigid wall around all plant cells. arbohydrates are a major source of energy for the body and so knowledge of their basic structure is very important in understanding energy metabolism. arbohydrates can be attached to other molecules, including proteins and lipids, and are present on the surface of cells where they can act as recognition molecules. 3.1 Introduction arbohydrates, as the name suggests, are molecules made up from carbon and water (hydrogen and oxygen). arbohydrates serve a number of important functions. They are a major source of energy for life. They are also important structural molecules in many organisms. Additionally, carbohydrates can be attached to other biological molecules, such as proteins, and in doing so modify the properties of the molecule. Probably the most abundant organic molecule on earth is the carbohydrate cellulose, a major constituent of plant cell walls. Sugars are small carbohydrates and these can be joined together to form oligosaccharides and polysaccharides. Different sugars can be joined together in many different ways to give rise to a very diverse array of structures. 3.2 Monosaccharides The simplest sugars are monosaccharides, which have the general formula ( 2 ) n. According to the value of n, sugars are described as trioses, pentoses, hexoses etc. An important sugar in energy metabolism is glucose. This is a hexose with the formula Monosaccharides such as glucose can occur as mirror image D and L isomers (enantiomers), similar to amino acids (see Fig. 3.1). D or L refers specifically to the arrangement of groups at the asymmetric carbon furthest from the aldehyde group (carbon 5 in glucose).

8 14 atch Up Biology D-glucose 6 2 L-glucose Figure 3.1. D and L glucose ther sugars, including mannose and galactose, share the same chemical formula as glucose but are not mirror image forms (Fig. 3.2). Glucose frequently assumes a ring form, as shown in Fig. 3.2, by the reaction of the aldehyde group on carbon 1 with the hydroxyl group on carbon 5. The glucose ring can also be found in either alpha or beta form, according to the arrangement of the group attached to the first carbon atom. In alpha (a) 2 2 Glucose Mannose (b) 2 2 β form α form Figure 3.2. (a) Glucose and mannose in open chain form; (b) Glucose in ring form

9 hapter 3 arbohydrates 15 glucose the group is below the plane of the ring, whereas in beta glucose it is above the plane of the ring. This minor structural difference has important consequences for the properties of the molecules and their polymers. Starch is a polymer of alpha glucose molecules and cellulose is a polymer of beta glucose. Note that humans have digestive enzymes that can degrade starch but are unable to digest cellulose. Sugars may also contain additional groups. Glucosamine is a derivative of glucose in which an amino (N 2 ) group replaces one of the groups. The amino group frequently has an additional acetyl group ( 3 ) attached to it, forming N-acetyl glucosamine. Another important glucose derivative is glucuronic acid, which contains a carboxylic acid group. Sugar derivatives such as N-acetyl-glucosamine and glucuronic acid are present in glycosaminoglycans, which are an important component of the extracellular matrix (see hapter 15). 3.3 Glycosidic bond When sugars join together to form oligosaccharides or polysaccharides this creates a glycosidic bond. A glycosidic bond is formed by the interaction of an group on one sugar with an group on another sugar. This involves the elimination of water and is therefore a condensation reaction. Enzymes that can break down glycosidic bonds are termed glycosidases. In comparison to the peptide bond, which is always formed between the N 2 and groups on the alpha carbon of an amino acid, there is much greater diversity in the way in which glycosidic bonds can form. Different carbon atoms can be involved, and an individual sugar can participate in multiple glycosidic bonds to give rise to branched structures. The bond is described according to the particular carbon atoms involved and whether the hydroxyl groups are in the alpha or beta position. In starch the glucose units are joined by a-1,4 linkages (Fig. 3.3), which means that the reaction involves the group on carbon 1 of one sugar reacting with the group on carbon 4 of the next. Glycosidases are highly specific for a particular type of glycosidic linkage.

10 16 atch Up Biology dehydration Figure 3.3. Formation of an a-1,4 glycosidic bond 3.4 Polysaccharides Polysaccharides consist of many monosaccharide subunits covalently linked together. They may involve one or more different sugar units and can be either linear or branched in structure. Starch is a storage polysaccharide of plants that plays an important role in the human diet. Starch has two components amylose, which is a linear polymer of glucose joined by a-1,4 linkages, and amylopectin, which is similar but also contains branches due to additional a-1,6 linkages occurring at points along the chain (Fig. 3.4). The enzyme that digests starch is called amylase and is present in saliva and in the small intestine. 2 1' 1,6 linkage 6' 2 2 1' 4' 1,4 linkage Figure 3.4. a-1,4 and a-1,6 linkages in glycogen

11 hapter 3 arbohydrates 17 Mammals store carbohydrates in the form of glycogen and this can be found in the liver and in muscle. Glycogen is similar in structure to amylopectin but is more branched. ellulose is an unbranched polymer of glucose linked by b-1,4 glycosidic bonds and is an important structural component of the cell walls of plants. umans do not have an enzyme that can hydrolyse this type of linkage and cannot use cellulose as an energy source. owever, cellulose does play an important role in digestive function as a source of roughage, or insoluble matter, helping to maintain the consistency of the faeces and to stimulate mucus secretion as waste matter passes through the large intestine. Ruminants, such as cattle and sheep, are able to make use of cellulose because they harbour bacteria that secrete the enzyme cellulase in a part of their digestive tract known as the rumen. 3.5 Glycoconjugates ther molecules may also have sugars attached to them a process known as glycosylation. Many proteins are glycosylated, particularly those that are found in cell membranes or that are secreted from the cell. Glycoproteins contain one or more oligosaccharides attached to the protein backbone, either at the hydroxyl group of serine or threonine residues (when they are described as -linked) or via the amide group of asparagine (N-linked). The relative amount of carbohydrate in glycoproteins varies enormously, from merely 1 or 2% to over 70%. Mucin is a very large and heavily glycosylated molecule that forms a major constituent of mucus and contributes to its gellike properties. Mucin contains a very high proportion of carbohydrate in the form of -linked oligosaccharides. Lipids may also be glycosylated. linical example: AB blood groups The human AB blood group antigens are oligosaccharides present on glycoproteins and glycolipids on red blood cells. Blood group specificity is defined by the oligosaccharide component. Enzymes called glycosyl transferases are required for the synthesis of oligosaccharides. These are highly specific and whether an individual produces the blood group oligosaccharide, A or B will depend on which glycosyl transferases they have inherited from their parents. If an individual with type blood were to receive a transfusion of type A blood then their immune system would react against the A oligosaccharide, destroying the transfused cells and leading to serious consequences.

12 18 atch Up Biology 3.6 Functions of carbohydrates arbohydrates serve a range of biological functions, several of which have been referred to above. They are an important part of the diet, providing a ready source of energy. In the form of polysaccharides such as starch and glycogen they play a role in storage. They are also important structural components of cells (e.g. cellulose) and influence the mechanical properties of tissues or secretions (e.g. glycosaminoglycans, mucins). Sugars are also important recognition molecules. Within the cell, the carbohydrates on glycoproteins play a role in ensuring that these molecules are transferred to the appropriate cellular compartments. arbohydrates present on cell surface glycoproteins and glycolipids also interact with proteins called lectins. This type of interaction plays an important role in the trafficking of white blood cells to sites of infection (see hapter 25). ligosaccharides also play an important role in the recognition of an egg by a sperm (see hapter 11). 3.7 Test yourself The answers are given on p Question 3.1 What is the chemical formula for glucose? Question 3.2 What is the name of the bond that joins sugars together in a polysaccharide? Question 3.3 What is the enzyme that degrades starch called? Question 3.4 What are the enzymes that synthesise oligosaccharides? Question 3.5 What polymer is used to store carbohydrates in animals?

13 BILGY BILGY BILGY atch Up Biology covers the basic principles and concepts in biology that you will need if you are studying medicine or a related subject, or one of the biomedical sciences. The book focuses on human biology and covers: the basic molecules of life, such as proteins, carbohydrates, nucleic acids cells, tissues and processes, including energy metabolism, cell division, epithelial and connective tissues the key mammalian systems, for example, homeostasis, the endocrine, respiratory and digestive systems F R TE MEDIAL SIENES P IL IP BR A DL E Y & J A NE A LV ER T Throughout the book the authors highlight clinical examples so that you can see the relevance of basic biology to your course. The book also contains questions (and answers) so that you can test your understanding of the subject as you work through the book. This new edition features two new chapters on microorganisms and on genetic disease. atch Up Biology is the ideal book to refresh your understanding of the basic concepts of biology. R E V IE W S F T E F IR S T E DI T IN: extremely useful at university, a very in depth book, just what s required EMISTRY w w w. s c i o n p u b l i s h i n g. c o m MI T F R Y A ND EL IZ A BE T PA GE MATS & STATS F R TE LIFE AND MEDIAL SIENES F R TE LIFE AND MEDIAL SIENES ISBN M. A R R I S, G. TAY L R & J. TAY L R BR A DL E Y & A LV ER T I have enjoyed reading this book and have found it highly informative. I have studied Biology in a formal context, but this was some years ago. I bought this book in order to better inform my grasp of biology before applying for a Medical Degree S E ND EDI T IN

14 ontents Preface Acknowledgements xi xii The molecules of life 1 Water and life The properties of water Water in the human body Test yourself 3 2 Proteins Introduction Primary structure Secondary structures Tertiary structure Quaternary structure Domains Functions of proteins onformational change Test yourself 12 3 arbohydrates Introduction Monosaccharides Glycosidic bond Polysaccharides Glycoconjugates Functions of carbohydrates Test yourself 18 4 Lipids Introduction Fatty acids Triglycerides and phospholipids holesterol Functions of lipids Test yourself 22 5 Nucleic acids and genes Introduction DNA and RNA DNA synthesis RNA synthesis The genetic code Protein synthesis 27

15 vi atch Up Biology 5.7 Introns and exons Regulation of gene expression Test yourself 31 ells and tissues 6 The cell Introduction Eukaryotic cells ell specialisation Test yourself 37 7 Microorganisms Introduction Bacteria Viruses Fungi ther infectious agents Treatment of infectious disease Test yourself 47 8 Energy metabolism Introduction The citric acid cycle Release of energy from fats and proteins xidative phosphorylation Anaerobic respiration Test yourself 53 9 Membrane transport Introduction smosis Facilitated diffusion Active transport Exocytosis and endocytosis Test yourself ell division and mitosis Introduction ell cycle ontrol of cell division ell division and differentiation Test yourself Reproduction Introduction Sexual reproduction Fertilisation Reproductive and therapeutic cloning Test yourself Inheritance Introduction 73

16 ontents vii 12.2 Definition of terms Mutations Mendelian inheritance Monohybrid inheritance Dihybrid inheritance Linkage Autosomal and sex-linked genes Genetic fingerprinting Evolution by natural selection Test yourself Genetic disease Introduction ystic fibrosis: an autosomal recessive disease untington disease: an autosomal dominant disease aemophilia A: an X-linked recessive disease Asthma: a disease caused by multiple genes Genetic testing Gene therapy and genetic diseases Test yourself Epithelial tissues Introduction lassification Adhesion Test yourself onnective tissues Introduction Glycosaminoglycans Fibres ells Test yourself Excitable tissues Introduction Membrane potential Muscle Nerve Test yourself 105 Systems 17 omeostasis Introduction Regulation of plasma glucose Thermoregulation Test yourself The endocrine system Introduction Types of hormone 114

17 viii atch Up Biology 18.3 ell signal receptors Second messenger systems Endocrine glands ypothalamo-pituitary axis Posterior pituitary ther endocrine glands Test yourself The nervous system Introduction Structure of nervous system The brain The spinal cord Peripheral nervous system Test yourself The cardiovascular system Introduction Blood Plasma Red blood cells Platelets The heart The circulatory system Test yourself The respiratory system Introduction Structure of the respiratory system Respiration Gaseous exchange ontrol of respiration Test yourself The digestive system Introduction ral cavity Structure of the GI tube The stomach Small intestine and accessory glands Large intestine Test yourself The reproductive system Introduction Male reproductive system Spermatogenesis Female reproductive system ogenesis and the menstrual cycle opulation and fertilisation Implantation and pregnancy Birth 158

18 ontents ix 23.9 Test yourself The urinary system The kidney The bladder Test yourself The immune system Immune responses to infection Inflammation Lymphocytes and the specific immune response Diseases of the immune system Test yourself The musculoskeletal system Introduction Bone Regulation of calcium levels artilage The skeleton Synovial joints Muscles and locomotion Test yourself 174 Answers to test yourself questions 175 Glossary 179 Index 203

19 03 arbohydrates BASI NEPTS: arbohydrates range in structure from simple sugar molecules, such as glucose, to polymers of sugar molecules, such as those that constitute the rigid wall around all plant cells. arbohydrates are a major source of energy for the body and so knowledge of their basic structure is very important in understanding energy metabolism. arbohydrates can be attached to other molecules, including proteins and lipids, and are present on the surface of cells where they can act as recognition molecules. 3.1 Introduction arbohydrates, as the name suggests, are molecules made up from carbon and water (hydrogen and oxygen). arbohydrates serve a number of important functions. They are a major source of energy for life. They are also important structural molecules in many organisms. Additionally, carbohydrates can be attached to other biological molecules, such as proteins, and in doing so modify the properties of the molecule. Probably the most abundant organic molecule on earth is the carbohydrate cellulose, a major constituent of plant cell walls. Sugars are small carbohydrates and these can be joined together to form oligosaccharides and polysaccharides. Different sugars can be joined together in many different ways to give rise to a very diverse array of structures. 3.2 Monosaccharides The simplest sugars are monosaccharides, which have the general formula ( 2 ) n. According to the value of n, sugars are described as trioses, pentoses, hexoses etc. An important sugar in energy metabolism is glucose. This is a hexose with the formula Monosaccharides such as glucose can occur as mirror image D and L isomers (enantiomers), similar to amino acids (see Fig. 3.1). D or L refers specifically to the arrangement of groups at the asymmetric carbon furthest from the aldehyde group (carbon 5 in glucose).

20 14 atch Up Biology D-glucose 6 2 L-glucose Figure 3.1. D and L glucose ther sugars, including mannose and galactose, share the same chemical formula as glucose but are not mirror image forms (Fig. 3.2). Glucose frequently assumes a ring form, as shown in Fig. 3.2, by the reaction of the aldehyde group on carbon 1 with the hydroxyl group on carbon 5. The glucose ring can also be found in either alpha or beta form, according to the arrangement of the group attached to the first carbon atom. In alpha (a) 2 2 Glucose Mannose (b) 2 2 β form α form Figure 3.2. (a) Glucose and mannose in open chain form; (b) Glucose in ring form

21 hapter 3 arbohydrates 15 glucose the group is below the plane of the ring, whereas in beta glucose it is above the plane of the ring. This minor structural difference has important consequences for the properties of the molecules and their polymers. Starch is a polymer of alpha glucose molecules and cellulose is a polymer of beta glucose. Note that humans have digestive enzymes that can degrade starch but are unable to digest cellulose. Sugars may also contain additional groups. Glucosamine is a derivative of glucose in which an amino (N 2 ) group replaces one of the groups. The amino group frequently has an additional acetyl group ( 3 ) attached to it, forming N-acetyl glucosamine. Another important glucose derivative is glucuronic acid, which contains a carboxylic acid group. Sugar derivatives such as N-acetyl-glucosamine and glucuronic acid are present in glycosaminoglycans, which are an important component of the extracellular matrix (see hapter 15). 3.3 Glycosidic bond When sugars join together to form oligosaccharides or polysaccharides this creates a glycosidic bond. A glycosidic bond is formed by the interaction of an group on one sugar with an group on another sugar. This involves the elimination of water and is therefore a condensation reaction. Enzymes that can break down glycosidic bonds are termed glycosidases. In comparison to the peptide bond, which is always formed between the N 2 and groups on the alpha carbon of an amino acid, there is much greater diversity in the way in which glycosidic bonds can form. Different carbon atoms can be involved, and an individual sugar can participate in multiple glycosidic bonds to give rise to branched structures. The bond is described according to the particular carbon atoms involved and whether the hydroxyl groups are in the alpha or beta position. In starch the glucose units are joined by a-1,4 linkages (Fig. 3.3), which means that the reaction involves the group on carbon 1 of one sugar reacting with the group on carbon 4 of the next. Glycosidases are highly specific for a particular type of glycosidic linkage.

22 16 atch Up Biology dehydration Figure 3.3. Formation of an a-1,4 glycosidic bond 3.4 Polysaccharides Polysaccharides consist of many monosaccharide subunits covalently linked together. They may involve one or more different sugar units and can be either linear or branched in structure. Starch is a storage polysaccharide of plants that plays an important role in the human diet. Starch has two components amylose, which is a linear polymer of glucose joined by a-1,4 linkages, and amylopectin, which is similar but also contains branches due to additional a-1,6 linkages occurring at points along the chain (Fig. 3.4). The enzyme that digests starch is called amylase and is present in saliva and in the small intestine. 2 1' 1,6 linkage 6' 2 2 1' 4' 1,4 linkage Figure 3.4. a-1,4 and a-1,6 linkages in glycogen

23 hapter 3 arbohydrates 17 Mammals store carbohydrates in the form of glycogen and this can be found in the liver and in muscle. Glycogen is similar in structure to amylopectin but is more branched. ellulose is an unbranched polymer of glucose linked by b-1,4 glycosidic bonds and is an important structural component of the cell walls of plants. umans do not have an enzyme that can hydrolyse this type of linkage and cannot use cellulose as an energy source. owever, cellulose does play an important role in digestive function as a source of roughage, or insoluble matter, helping to maintain the consistency of the faeces and to stimulate mucus secretion as waste matter passes through the large intestine. Ruminants, such as cattle and sheep, are able to make use of cellulose because they harbour bacteria that secrete the enzyme cellulase in a part of their digestive tract known as the rumen. 3.5 Glycoconjugates ther molecules may also have sugars attached to them a process known as glycosylation. Many proteins are glycosylated, particularly those that are found in cell membranes or that are secreted from the cell. Glycoproteins contain one or more oligosaccharides attached to the protein backbone, either at the hydroxyl group of serine or threonine residues (when they are described as -linked) or via the amide group of asparagine (N-linked). The relative amount of carbohydrate in glycoproteins varies enormously, from merely 1 or 2% to over 70%. Mucin is a very large and heavily glycosylated molecule that forms a major constituent of mucus and contributes to its gellike properties. Mucin contains a very high proportion of carbohydrate in the form of -linked oligosaccharides. Lipids may also be glycosylated. LINIAL EXAMPLE: AB BLD GRUPS The human AB blood group antigens are oligosaccharides present on glycoproteins and glycolipids on red blood cells. Blood group specificity is defined by the oligosaccharide component. Enzymes called glycosyl transferases are required for the synthesis of oligosaccharides. These are highly specific and whether an individual produces the blood group oligosaccharide, A or B will depend on which glycosyl transferases they have inherited from their parents. If an individual with type blood were to receive a transfusion of type A blood then their immune system would react against the A oligosaccharide, destroying the transfused cells and leading to serious consequences.

24 18 atch Up Biology 3.6 Functions of carbohydrates arbohydrates serve a range of biological functions, several of which have been referred to above. They are an important part of the diet, providing a ready source of energy. In the form of polysaccharides such as starch and glycogen they play a role in storage. They are also important structural components of cells (e.g. cellulose) and influence the mechanical properties of tissues or secretions (e.g. glycosaminoglycans, mucins). Sugars are also important recognition molecules. Within the cell, the carbohydrates on glycoproteins play a role in ensuring that these molecules are transferred to the appropriate cellular compartments. arbohydrates present on cell surface glycoproteins and glycolipids also interact with proteins called lectins. This type of interaction plays an important role in the trafficking of white blood cells to sites of infection (see hapter 25). ligosaccharides also play an important role in the recognition of an egg by a sperm (see hapter 11). 3.7 Test yourself The answers are given on p Question 3.1 What is the chemical formula for glucose? Question 3.2 What is the name of the bond that joins sugars together in a polysaccharide? Question 3.3 What is the enzyme that degrades starch called? Question 3.4 What are the enzymes that synthesise oligosaccharides? Question 3.5 What polymer is used to store carbohydrates in animals?