With its engaging and authoritative text featuring insightful clinical cases, graphic narratives, SBAs and a wealth of other learning tools, the book has everything you need to succeed in your studies and pass your exams.
The book starts with a First Principles chapter which clearly explains the key concepts and mechanisms relevant to the study of medicine e.g. types of biochemical reaction, enzymes and cofactors.
This is followed by a series of systems-based chapters which are introduced with an engaging clinical case which helps link the subject to the practice of medicine.
Finally there is a self-assessment chapter consisting of 80 single best answer questions to test your understanding.,
With its engaging and authoritative text featuring insightful clinical cases, graphic narratives, SBAs and a wealth of other learning tools, the book has everything you need to succeed in your studies and pass your exams.
The book starts with a First Principles chapter which clearly explains the key concepts and mechanisms relevant to the study of medicine e.g. types of biochemical reaction, enzymes and cofactors.
This is followed by a series of systems-based chapters which are introduced with an engaging clinical case which helps link the subject to the practice of medicine.
Finally there is a self-assessment chapter consisting of 80 single best answer questions to test your understanding.,
Eureka: Biochemistry and Metabolism
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Eureka: Biochemistry and Metabolism
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Overview
With its engaging and authoritative text featuring insightful clinical cases, graphic narratives, SBAs and a wealth of other learning tools, the book has everything you need to succeed in your studies and pass your exams.
The book starts with a First Principles chapter which clearly explains the key concepts and mechanisms relevant to the study of medicine e.g. types of biochemical reaction, enzymes and cofactors.
This is followed by a series of systems-based chapters which are introduced with an engaging clinical case which helps link the subject to the practice of medicine.
Finally there is a self-assessment chapter consisting of 80 single best answer questions to test your understanding.,
Product Details
| ISBN-13: | 9781907816833 |
|---|---|
| Publisher: | Scion Publishing Ltd. |
| Publication date: | 03/07/2020 |
| Edition description: | 1 |
| Pages: | 288 |
| Product dimensions: | 6.30(w) x 9.45(h) x 0.50(d) |
Read an Excerpt
CHAPTER 1
First principles
Introduction 1
Overview 1
Cell structure 3
Cell membranes and the transport of molecules and ions 8
Signalling pathways 14
Enzymes and cofactors 20
Biochemical bonds and reactions 26
Body fuels 32
Introduction
Biochemistry is the study of all chemical and molecular processes occurring in the body, including:
* anabolism (building molecules)
* catabolism (breaking molecules down)
* molecular transport
* generation of energy
These reactions primarily use the key biological molecules carbohydrates, lipids, proteins and nucleic acids. Knowledge of how the body synthesises, uses and stores these molecules is fundamental to understanding normal body function and the mechanisms by which it goes wrong in disease states. In particular, an understanding of biochemical processes underlies many clinical investigations, diagnoses and treatments.
The cell is the basic unit of life, and the place in which and between which these processes occur. The body comprises about 100 trillion cells, each only 1–100 µm in diameter. All the cells in an individual person contain identical hereditary material for their design: the deoxyribonucleic acid (DNA) that encodes genes. Despite this, there are hundreds of different types of cell. Biochemistry is the story of how these living building blocks operate and communicate at the chemical level, and is key to understanding how and why they dysfunction.
Overview
Starter questions
Answers to the following questions are on page 39.
1. How many types of cell are there?
2. What is a stem cell?
Fundamental to biochemical processes are the molecular interactions between molecules, cells, tissues and organs. The body is composed of organs, which consist of tissues, which in turn are made of cells. Each cell contains organelles that have specific functions, and each cell is capable of numerous chemical reactions to provide usable energy. The energy provided is utilised to coordinate cellular activities and ultimately tissue and organ functions. This chapter focuses on the basic principles that govern these processes and functions.
Body systems
The average human contains over 1014 cells organised into tissues or organs, which form systems:
* the respiratory system to take up oxygen and remove carbon dioxide
* the gastrointestinal system to digest food and absorb nutrients
* the urinary system to remove waste products
* the cardiovascular system to transport oxygen and nutrients and to regulate temperature, blood pressure, electrolytes and water balance
* the reproductive system to enable procreation
* the nervous and endocrine systems to coordinate and integrate the functions of the other systems
Each system operates at a system, organ, tissue, cellular, organelle and molecular level to maintain its functions, and each is integrated in the whole organism through interorgan and intercellular communication, for example through chemical messengers called hormones.
Cells
Metabolic processes take place throughout the body and occur predominantly in cells. This compartmentalisation enables metabolites to be concentrated; their distribution regulated and also protects the body from harmful metabolites.
A cell is the fundamental unit of an organism. It is a microscopic membrane-bound sac of fluid and solid components, and its development and function depend on the controlled expression of the DNA it contains.
There are two main types of cell in organisms: prokaryotes (bacteria) and eukaryotes (animals, plants and micro-organisms). Eukaryotes have a nucleus, organelles and a compartmentalisation of materials, whereas prokaryotes do not. Both cell types have similar biochemical composition and share many metabolic pathways but are different in terms of structural elements and genetic processes (Table 1.1).
An understanding of basic cell biology and the processes that occur in individual organelles is key to understanding cellular events at the molecular level. Organelles can be considered specialised subunits in a cell, much like organs are functional units in an organism.
Cell structure
Starter questions
Answers to the following questions are on page 39.
3. Why are cell membranes both hydrophobic (water repelling) and hydrophilic (interact with water)?
4. How do cells die and how many die per day?
All eukaryotic cells have certain structures in common, such as a plasma membrane. However, specialised cells have additional features related to their function, such as the moving, high-surface area folds called villi in intestinal cells, which aid the absorption of intestinal contents. Cells are highly organised internally, with numerous organelles, each of which has a specific function (Figure 1.1).
Cell polarity
Cell polarity is the term for the asymmetrical organisation of cells, with differences in the properties of the cell surface, cell organelles and cytoskeleton at different ends. These differences reflect the function and location of the cells. For example, the epithelial cells of the intestine have two surfaces: the apical surface and the basolateral surface. Each is exposed to a different environment, and they differ both structurally and chemically.
The apical surface faces inwards towards the lumen, whereas the outer (basolateral) surface is exposed to extracellular fluids, facing outwards. The basolateral membrane is in contact with the basal lamina externally.
The two surfaces are evident in epithelial and endothelial cells. The basolateral membrane of a polarised cell is the surface of the plasma membrane that forms its basal and lateral surfaces. It faces outwards, away from the lumen. Thus the cell has apical-basal polarity that enables specialised diffusion and transport for ions and other macromolecules.
Cell membrane
Every cell is surrounded by a plasma membrane that separates the inside of the cell from the extracellular environment. It consists of lipids and proteins, which provide flexibility, motility and permeability.
Generally, biochemical processes occur more efficiently in an aqueous medium (a watery environment) because this facilitates movement of and interaction between substances. Therefore intracellular fluid, blood and other body fluids are aqueous environments.
To enable control of extracellular and intracellular environments, cells require a barrier through which water flow is controlled: the cell membrane. The cell membrane makes control possible because it is semipermeable: it selectively allows the passage of a limited number of substances. Membrane permeability is regulated by the lipid composition of the membrane and the proteins (ion channels and transport proteins) embedded in the lipid bilayer.
As well as isolating and controlling the intracellular environment, the cell membrane has other key roles, including:
* energy storage
* cell signalling
* cell adhesion
* anchoring of extracellular structures and the intracellular cytoskeleton
* ion conductivity
* membrane transport
The cell membrane protects the cytoplasm, also called cytosol, the large fluid-filled space inside the cell. In this fluid are all the organelles and the cytoskeleton.
Cytoplasm
The cytoplasm contains dissolved nutrients, helps break down waste products and moves material around the cell. It also contains salts, which make it a good conductor of electricity. Chemically the cytoplasm is 90% water and 10% proteins, carbohydrates, lipids and inorganic salts, providing a suitable environment for cellular function. The cytoplasm is predominantly fluid, and its flow is directed to transport molecules and organelles through cytoplasmic streaming.
In the cytoplasm are the organelles, the most prominent of which is the nucleus.
The nucleus
The nucleus is the largest organelle, occupying up to half the cell volume. It is the operational centre of the cell because it contains DNA, the blueprint for the structure of the cell and the software for cell function.
The nucleus is separated from the cytoplasm by a protective double membrane called the nuclear envelope. This comprises two closely spaced membranes containing several hundred nuclear pore complexes. These pores allow macromolecules (larger molecules such as ribosomes, RNA and DNA polymerase enzyme) to move into and out of the nucleus. The nuclear envelope also protects the cell's DNA.
All cells have a nucleus except for red blood cells, which lose their nucleus on maturation. The lack of the nucleus enables the cell to develop the specific doughnut shape required to transport oxygen.
Chromosomes
The eukaryotic nucleus contains DNA organised into chromosomes. Each cell has the same DNA content (the genome) organised into the same number of chromosomes, unless there is a genetic abnormality.
Each chromosome consists of a single DNA molecule associated with numerous proteins. Humans have 46 chromosomes in 23 pairs, including one pair of sex chromosomes: XX in females and XY in males. The sex chromosomes carry information for sexual differentiation as well as other 'sexlinked' traits. The other 22 pairs, the autosomes, contain the rest of the genetic hereditary information.
Human cells are diploid, because each autosome is present in two copies. The cells of other organisms sometimes have more than two copies. This is especially common in plants, which can be hexaploid (e.g. in bread wheat) or tetraploid (e.g. durum wheat).
Ribosomes
Ribosomes are ribonucleoproteins; they consist of nucleic acid and protein. They are the machines that synthesise (or translate) proteins from messenger ribonucleic acid (mRNA), the messenger molecule that is transcribed from the DNA in the nucleus and then leaves through the nuclear pores (see Chapter 2).
Each ribosome comprises a large subunit and a small subunit. Each subunit is composed of proteins and one or more molecules of ribosomal RNA (rRNA). The small subunit reads the mRNA sequence, whereas the large subunit joins the amino acids encoded by the mRNA into a polypeptide chain.
The cell's ribosomes are either free in the cytoplasm or bound to another organelle called the endoplasmic reticulum. The bound ribosomes give the endoplasmic reticulum a rough appearance, hence the term rough endoplasmic reticulum.
Ribosomes have the same function whether free or bound. However, they synthesise different proteins, being controlled by signal sequences on the protein.
* Proteins synthesised by free ribosomes are released into the cytosol for use in the cell
* Proteins produced from bound ribosomes are usually used in the plasma membrane or are expelled from the cell through exocytosis (see page 13)
Endoplasmic reticulum
The endoplasmic reticulum is part of the cell's transport network for molecules, an interconnected network of membrane vesicles held together by the cytoskeleton. It has three forms:
* rough endoplasmic reticulum
* smooth endoplasmic reticulum
* sarcoplasmic reticulum
Rough endoplasmic reticulum has ribosomes on its surface and synthesises proteins for release, through the Golgi apparatus, to their destination.
Smooth endoplasmic reticulum does not have ribosomes. It has roles in lipid and carbohydrate metabolism, steroid metabolism, detoxification and calcium sequestration and release.
The functions of the endoplasmic reticulum vary depending on cell type, cell function and cell requirements. The cell can respond to changes in its metabolic needs, for example by adjusting the relative amounts of rough and smooth endoplasmic reticulum.
Sarcoplasmic reticulum is a type of smooth endoplasmic reticulum present in the myocytes (muscle cells) of smooth and striated muscle. It has a major role in excitation–contraction coupling, the molecular mechanism of muscular contraction. Its role is to collect and release calcium when the muscle cell is stimulated; the calcium ions are used to provoke muscular contraction. To carry out its functions, the sarcoplasmic reticulum has special membrane proteins not present in normal smooth endoplasmic reticulum.
The Golgi apparatus
The Golgi apparatus, also called the Golgi complex, is a folded membrane organelle that alters, sorts and packages newly made macromolecules such as proteins and lipids for secretion or for use in the cell. It also produces lysosomes, the small, membrane-bound vesicles (sacs) that contain digestive enzymes that break down unwanted molecules in the cytosol.
The Golgi apparatus consists of stacks of membrane cisternae: flat discs of folded membrane, with four to eight cisternae per stack and 40–100 stacks per cell. Each cisterna contains enzymes used to modify the proteins, which it then packs and transports.
Mitochondria
Mitochondria are self-replicating organelles that are present in various numbers, shapes and sizes in all eukaryotic cells. Their main role is to generate cellular energy by oxidative phosphorylation (see page 112). Oxidative phosphorylation is a chain reaction that occurs in the inner membrane of the mitochondria; oxygen is used to release energy from compounds, typically glucose, to generate adenosine triphosphate (ATP).
Other functions of mitochondria include regulation of programmed cell death (apoptosis), cell signalling, cellular differentiation and regulation of the membrane potential. The membrane potential is the difference in voltage inside and outside the cell; changes in membrane potential enable cells to send chemical and electrical messages around the body, and to and from the central nervous system. Different cells have different numbers of mitochondria. For example, erythrocytes are the only cells without them, and neurons and spermatozoa contain many.
Mitochondria are sausage-shaped (Figure 1.2), 0.5–10 µm long and have five distinct features:
* an outer membrane
* an intermembrane space
* an inner membrane
* cristae, the folds of the inner membrane that contain the enzymes that catalyse oxidative phosphorylation
* a matrix, the central space, which contains mitochondrial DNA
The outer membrane
The mitochondrial outer membrane contains many integral porins. Porins are proteins that form channels for small molecules (= 5 kDa), thus making the membrane freely permeable to them. Because small molecules are able to diffuse freely across the outer membrane, the concentration of these molecules in the intermembrane space is equal to that in the cytosol.
Larger proteins are moved across the membrane by the translocase protein complex, which includes 19 proteins. This occurs by active transport, so energy is required in the form of ATP.
The intermembrane space
Cytochrome c is a protein in the intermembrane space with an essential role in the electron transport system, also known as the electron transport chain. This is the series of reduction–oxidation (redox) reactions between inner membrane proteins that produces most of the body's ATP. Cytochrome c also helps initiate apoptosis, the programmed cell death that ends the cell's life cycle and prevents disordered cell growth and behaviour.
The inner membrane
As well as being the fundamental site of the electron transport system, the inner membrane contains cardiolipin, a phospholipid (see page 9) also present in bacterial membranes. Cardiolipin contains four fatty acids instead of the two normally present on phospholipids; this property contributes to the impermeable nature of the inner membrane.
The inner membrane has no porins, so all ions and molecules require special membrane transport mechanisms to enter or exit the matrix. This property is central to the ability of the electron transport system to generate the concentration gradients that are exploited to generate ATP.
Cristae
Cristae are folds of inner membrane that provide an increased surface area for ATP production through the electron transport system. The number of folds varies according to the energy demand of the tissue or cell. For example, liver and muscle cells have many cristae, reflecting their higher energy demands.
Matrix
The mitochondrial matrix is the central space and contains two thirds of the total protein content of the mitochondria. It is the site of the citric acid cycle (also known as the tricarboxylic acid cycle or Krebs cycle), the oxidation of fatty acids and pyruvate, and all processes of ATP production.
Lysosomes
Lysosomes are large, irregular vesicular structures in the cytoplasm. They break down old cell components and bacteria with degradative enzymes and acidic fluid bound by the lysosomal membrane. They engulf objects by endocytosis (cell takes up material; an energy dependent process) and phagocytosis (form of endocytosis whereby bacteria are internalised). They also help repair torn sections of plasma membrane by functioning as a 'patch'.
Peroxisomes
Peroxisomes are vesicular structures, 0.5 nm in diameter, required in synthetic (anabolic) and degradative (catabolic) processes. They contain more than 40 peroxisomal enzymes.
One major function of peroxisomes is the ß-oxidation (i.e. breakdown) of very-long chain fatty acids (with = 22 carbons) to medium-chain fatty acids (6–10 carbons long). The shorter fatty acids are then transported to the mitochondria for further degradation. Peroxisomes are also the site of the breakdown of branched chain fatty acids, D-amino acids and polyamines.
Peroxisomes are also the site of anabolic activity.
(Continues…)
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