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Introduction 1 OVERVIEW OF THE BOOK Organelles and their function Within each cell are a number of highly organized physical Anatomy and physiology are two essential sciences of med- structures—organelles—each with a specific function (see icine. Anatomy is the understanding of the structure of or- Fig. 1.1). ganisms and their parts, from gross structures such as the Nucleus bones of a limb to the microstructures of an individual cell. The nucleus is present in almost all cells and is the ‘control Physiology is the understanding of the normal functions of centre’ (see Fig. 1.2). It stores and transmits information, in the human body, which all doctors must understand to treat the form of DNA, to the next generation. The genes within the diseases that occur when these functions go wrong. the cell’s nucleus determine the types of protein made by the As you progress through this book and into your career cell during its lifetime. in health care, you will repeatedly find that structure is in- trinsically related to function and vice versa. It therefore seemed only natural to combine the learning of anatomy and physiology into one concise text. This book will progress from introducing the building Microfilaments Golgi complex blocks of life and key concepts required to understand anat- omy and physiology, to describing the normal structure and function of the human body broken down into a sys- Mitochondria tems-based approach. The aim of this book is to allow the reader to gain a good understanding of the concepts of anat- Vesicles Lysosome omy and physiology that will be sufficient to pass medical Nucleus undergraduate exams. Rough Nucleolus endoplasmic Microtubules reticulum THE CELL Smooth endoplasmic Structure and function reticulum Fig. 1.1 Cell and organelles. Microstructure of the cell Protoplasm is the collective name given to the basic com- ponents and materials that make up the cell inside the cell membrane. The protoplasm therefore includes both the nu- Nuclear envelope Chromatin cleus and cytoplasm. The protoplasm is formed of: • Water—the major component of the cell, forming Nucleolus around 80% of the cell. • Proteins—form around 15% of the cell. The two types are: Rough • structural proteins, forming the body of the cell endoplasmic • globular proteins that are mainly enzymes. reticulum • Lipids—there are three main types of lipid in the cell: • phospholipids—form the outer and intracellular Inner membranous barriers membrane • cholesterol—integrated into the outer and Outer intracellular membranous barriers membrane • triglycerides—an energy source of the cell. • Carbohydrates—stored as glycogen and provide energy Nuclear envelope for the cell • Electrolytes—essential for cellular reactions (e.g., action potential): potassium ions (K+), magnesium ions (Mg2+), Phospholipid bilayer 3− − phosphate ions PO4 ) and bicarbonate ions (HCO3 ). Fig. 1.2 The cell nucleus and nuclear membrane structure. 1 Introduction Nuclear membrane and envelope Filaments These two membranes surround the nucleus, containing A cell’s shape is maintained by a cytoskeleton. This cytoskel- pores that regulate the entry and exit of molecules. eton is formed of protein filaments in the cytoplasm, which also act to aid cell movement. Nucleoli The nucleoli are highly coiled structures within the nucleus Energy production in the cell of the cell. They contain ribonucleic acid (RNA) and protein components. The nucleoli are not enveloped by a nuclear Cells use oxygen to break down macromolecules from food membrane. (carbohydrates to glucose, proteins to amino acids and fats to fatty acids) and form the compound ATP. ATP is the univer- Ribosomes sal source of energy for all intracellular metabolic reactions. Ribosomes are large organelles, composed of about 70 pro- teins and several RNA molecules, that serve as the site of Structure of adenosine triphosphate protein synthesis. They include two subunits of different ATP is a nucleotide containing the base adenine, the pentose sizes, 30 s and 50 s, the former being smaller. sugar ribose and three phosphate molecules (Fig. 1.3). The Proteins are synthesized from amino acid building end two phosphate molecules are connected by a high- blocks, using a genetic template derived from DNA that is energy bond. When broken, each liberates about 30.6 kJ/ carried from the nucleus to the ribosomes as RNA messen- mol of energy, roughly the same as the energy in a single ger molecules. The proteins are then released into the cyto- peanut. When the first covalent bond is hydrolysed, adenos- sol (fluid part of the cell’s cytoplasm) or transferred to other ine diphosphate (ADP) is produced; loss of another phos- organelles via the Golgi apparatus (see later). phate molecule forms adenosine monophosphate (AMP). Energy is released when each bond is hydrolysed. Endoplasmic reticulum The endoplasmic reticulum (ER) forms a network of mem- Formation of adenosine triphosphate brane within the cell. There are two types: The majority (95%) of ATP is formed in the mitochondrial 1. Rough (or granular) ER carries surface ribosomes. matrix. One molecule of glucose produces a net of 38 mol- Proteins are synthesized on the attached ribosomes, ecules of ATP during aerobic respiration. Other substrates enter the lumen of the ER and are subsequently can produce more ATP than carbohydrates. For example, distributed within the cell or secreted to other cells. 1 g of fat can produce twice as much ATP as 1 g of car- 2. Smooth (or agranular) ER does not have ribosomes bohydrate. Protein is used as a substrate only when all the on its surface. This type of ER synthesizes fatty acids carbohydrate and fat reserves have been utilized, i.e., in a and regulates cellular levels of calcium (Ca2+), which starvation state. There are four stages of ATP production: controls many of the cell’s activities. Glycolysis—Glycolysis is the formation of pyruvic acid (PA). Glucose, fatty acids and amino acids enter the cell cy- Golgi apparatus toplasm and are converted to PA, releasing energy for the These membranous sacs sort and modify proteins arriving formation of two molecules of ATP (Fig. 1.4). from the rough ER, packaging them into vesicles before Conversion of pyruvic acid to acetyl coenzyme A—PA sending them to other organelles with the cell, or secreting enters the mitochondrial matrix, where the enzyme pyru- them into the extracellular space. vate dehydrogenase changes transform it into acetyl coen- zyme A (acetyl-CoA) (Fig. 1.4). Mitochondria Krebs cycle—Krebs cycle is sometimes called the citric The mitochondria function to make energy available to acid or tricarboxylic acid cycle. Acetyl-CoA enters a series cells in the form of adenosine triphosphate (ATP). They are of chemical reactions in the mitochondrial matrix in which double-membraned, elongated structures with a smooth it is split into acetyl and CoA, as shown in Fig. 1.5. The outer membrane and an inner membrane that is folded into acetyl portion enters the cycle and the CoA is used in the tubes (cristae) designed to increase surface area. The cristae formation of more acetyl-CoA. During the Krebs cycle, for contain DNA for mitochondrial protein synthesis. every glucose molecule: Lysosomes Lysosomes are single-membraned organelles that contain highly acidic digestive enzymes that break down bacteria, Adenine cell debris and dead organelles. Peroxisomes PPP These single-membraned organelles destroy the highly Triphosphate Ribose toxic compound hydrogen peroxide (H2O2), a byproduct of certain cell reactions. Additionally, the peroxisomes in the OH– OH– liver and kidney produce H2O2 and use it to detoxify vari- ous ingested molecules. Fig. 1.3 Structure of adenosine triphosphate. 2 The cell 1 Fig. 1.4 Glycolysis and conversion of pyruvic glucose 2 ATP acid to acetyl coenzyme (acetyl-CoA). ADP, Adenosine diphosphate; ATP, adenosine 2 ADP triphosphate; NAD, nicotinamide adenine fructose dinucleotide; NADH, nicotinamide adenine G diphosphate dinucleotide hydrogen. Lactate l y c o PGAL PGAL l NAD NAD y In s presence NADH NADH i of no s oxygen 2 ADP 2 ADP 2 ATP 2 ATP pyruvic acid pyruvic acid NADH NAD Coenzyme A pyruvate Acetyl CoA Krebs cycle Pyruvate dehydrogenase CO2 Glucose (C6) • seven molecules of water are added • 16 hydrogen atoms and four molecules of carbon dioxide (CO2) are released • two molecules of ATP are formed. Pyruvic acid (C5) The CO2 diffuses out of the mitochondria and is expired as CO2 a waste gas from the lungs. Oxidative phosphorylation (electron transport Acetyl CoA chain)—The largest amount of ATP formation occurs during oxidative phosphylation (remember glycolysis and the Krebs cycle only contribute 4 of the 38 ATP molecules produced) (Fig. 1.6). There are seven main steps: 1. Hydrogen is split into a hydrogen ion (H+) and an Oxaloacetic acid Citric acid (C6) electron. NAD NADH2 2. The electron enters the electron transport chain on the inner mitochondrial membrane. NAD NADH2 3. The electron is transported from electron acceptor to Kreb's cycle electron acceptor (i.e., flavoproteins and cytochromes B, C and A) until it reaches cytochrome A3 (cytochrome oxidase). FADH2 CO 4. Cytochrome oxidase helps form ionic oxygen, which 2 + FAD combines with the H to form water. 5. The large amounts of energy that are released during NAD the electron transport chain happen because the + ATP electron transport pumps H from the inner matrix of NADH2 ADP + Pi CO2 the mitochondrion to the space between the inner and outer membrane (outer chamber). Fig. 1.5 Krebs cycle. ADP, Adenosine diphosphate; ATP, + adenosine triphosphate; CoA, coenzyme A; FAD, flavin 6. The high concentration of H in the outer chamber adenine dinucleotide; FADH, flavin adenine dinucleotide– flows over the enzyme ATPase, which is attached to reduced form; NAD, nicotinamide adenine dinucleotide; the inner mitochondrial membrane. This energy from + NADH, nicotinamide adenine dinucleotide–reduced form; the H flow is used by ATPase to convert ADP Pi, phosphate.
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