This chapter examines the pentose phosphate pathway, which is a pathway of glucose oxidation which does not generate adenosine triphosphate (ATP) nor oxidize a molecule of glucose completely. The chapter considers the pentose phosphate pathway as a versatile pathway that produces ribose-5-phosphate for nucleotide synthesis, supplies nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) for fat synthesis and other reductive systems, and provides a route for the metabolism of surplus pentose sugars coming from the diet. The pathway has an oxidative section converting glucose-6-phosphate into ribose-5-phosphate and it produces NADPH. The chapter explores how the nonoxidative section manipulates ribose-5-phosphate according to the needs of the cell. If a cell requires equal amounts of ribose-5-phosphate and NADPH, only the oxidative section is required.
Chapter
An alternative pathway of glucose oxidation: the pentose phosphate pathway
Chapter
Angiogenesis
This chapter focuses on the process of forming new blood vessels from pre-existing ones by the growth and migration of endothelial cells — angiogenesis. It argues that this process is common during embryogenesis, although it rarely occurs in the adult. The chapter then shows why angiogenesis is essential for most tumors with respect to cancer. It explains the angiogenic switch and the mechanisms of angiogenic sprouting. Sprouting of pre-existing vessels requires major reorganization involving destabilization of the mature vessel, proliferation and migration of endothelial cells, and maturation. It is regulated by the interaction of soluble mediators and their cognate receptors. The chapter then presents the other means of tumor neovascularization and elaborates on anti-angiogenic therapy. It then looks at vascular targeting by vascular disrupting agents.
Chapter
Apoptosis
This chapter begins with a description of apoptosis. It defines apoptosis as a type of “cell suicide” that is intrinsic to the cell. It is an active process requiring the expression of genetically encoded proteins that every cell is capable of executing. The chapter then chronicles the molecular mechanisms of apoptosis and examines specific mutations that affect the apoptotic pathway and play a role in carcinogenesis. It also investigates how mutations in the apoptotic pathway can lead to resistance to chemotherapeutic drugs. Next, the chapter presents strategies for the design of new cancer therapeutics that target apoptosis. It also studies how caspases play a central role in apoptosis.
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The basic molecular themes of life
This chapter talks about living cells. These obey the laws of physics and chemistry. Energy is derived in cells from the breaking down of food molecules and released in a form that can drive chemical and physical work. The chapter considers adenosine triphosphate (ATP) as the universal energy currency in life. Energy from food breakdown is used to synthesize ATP from adenosine diphosphate (ADP) and phosphate. ATP breakdown can then be coupled to carry out biochemical work. The chapter analyses biological molecules which are based on the carbon atom bonded mainly to hydrogen, oxygen, nitrogen, and other carbon atoms. Noncovalent bonds are weak in comparison with covalent bonds but important in allowing interactions between molecules.
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Biochemical techniques
This chapter reviews the different biochemical techniques. The experimental procedures by which biochemical information is obtained include molecular biological, immunological, biochemical, and biophysical techniques. Molecular biology techniques involve the analysis and manipulation of DNA, RNA, and protein. They include cloning genes/complementary DNAs; genomics/genome sequencing; gene therapy; and genetically modified (GM) crops. The chapter then looks at protein purification and analysis. It also considers immunological techniques, which exploit the high specificity and affinity of antibodies for their cognate antigen. They can be used simply to analyse the presence of a protein, examine post-translational modifications, probe protein–protein interactions, and interactions of protein with other macromolecules. Finally, the chapter studies biophysical techniques, which allow analysis of the structure and physical properties of biochemical macromolecules.
Book
Despo Papachristodoulou, Alison Snape, William H. Elliott, and Daphne C. Elliott
Biochemistry and Molecular Biology is made up of six parts. Part 1 covers the basic concepts of life. Part 2 is about the structure and function of proteins and membranes. The third part looks at metabolism and nutrition. The fourth part of the book covers information storage and utilization. The fifth part looks at cells and tissues. Finally, the sixth part is about protective mechanisms against disease such as blood clotting, xenobiotic metabolism, reactive oxygen, and the immune system.
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The biogenesis and nucleocytoplasmic traffic of non-coding RNAs
This chapter explores non-coding RNAs (ncRNAs) that are processed during their biogenesis. It covers the processing and maturation of ribosomal RNA (rRNA), small nuclear RNA (snRNA), transfer RNA (tRNA), mitochondrial transcripts, and telomerase. It also gives an overview of the important aspects of RNA processing, including the RNA processing machinery that involves the action of other RNA molecules. The chapter reviews the main features of the biogenesis of ribosomal RNA, which is a process that is facilitated by a family of small RNA molecules known as the small nucleolar RNAs (snoRNAs). It describes the organization of rRNA processing in an important multifunctional nuclear organelle, the nucleolus.
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Biological membranes
This chapter highlights biological membranes, which form the boundary of the cell and separate it from its external environment. It explains that membranes are composed mainly of lipids and proteins and clarifies that the accepted structure of biological membranes is described by the fluid mosaic model. It also notes how archaeal membranes differ from those of eucarya and bacteria as they lack fatty acid residues. It notes that proteins of archaeal membranes are arranged in a similar manner to those of bacteria and eukaryotes. The chapter considers membranes as asymmetric structures, such as the carbohydrate of plasma membranes which is found attached in glycoproteins and glycolipids of the outer leaflet. It discusses the major general function of the lipid bilayer, which forms a permeability barrier around cells.
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Biological molecules
This chapter reviews how molecules are built up by linking atoms together with covalent bonds and explores the way in which molecules interact with one another non-covalently in the aqueous environment of the cell. There are four major classes of biological molecules that play essential roles in all organisms: nucleotides, amino acids, carbohydrates, and lipids. Each of them can be found in cells both as individual small molecules or covalently linked to form larger molecules known as polymers or macromolecules. Nucleic acids are polymers of nucleotides that are responsible for carrying genetic information. Proteins, on the other hand, are polymers of amino acids that function as workhorses, carrying out most of the chemical reactions in the cell and giving cells their structure and shape. Many biological molecules can be covalently modified in ways that alter their chemical properties and allow their function to be regulated.
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Blood cell genesis: red cell, white cell and platelet families
Gavin Knight
This chapter evaluates the types of blood cell found within peripheral blood. It begins by explaining blood cell production and the structure of the bone marrow. The red colouration of our blood is derived from the red blood cells, also called erythrocytes, and in particular the intracellular respiratory pigment haemoglobin. Meanwhile, our capacity to fight infection comes from heterogeneous populations of white blood cells, also called leucocytes, with each population having a different function. Under the umbrella term of white blood cells are three types of cell characterized by the types of granule within their cytoplasm. These cells are broadly called granulocytes, and more specifically are neutrophils, eosinophils, and basophils. The chapter then looks at stem cells, haemopoiesis, erythropoiesis, thrombopoiesis, haemostasis, granulopoiesis, and monopoiesis.
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Blood clotting, xenobiotic metabolism, and reactive oxygen species
This chapter describes a number of processes in the body which are essential protective devices against different hazards. It mentions blood clotting. This involves two separate pathways of proteolytic enzymes, which converge at active factor X. This process activates prothrombin to thrombin, a proteolytic enzyme that converts fibrinogen to fibrin. Fibrin is a fibrous complex that entraps blood cells into a soft clot, which is then stabilized by cross-link formation between the strands. The chapter looks at the pathway that is triggered by a wound exposing an abnormal surface, such as collagen. The shorter extrinsic pathway results from the release of a factor from damaged cells.
Book
Aysha Divan and Janice Royds
The Cancer Challenge provides an overview of key milestones in the history of cancer research, our current understanding of the disease, and future directions in its diagnosis and treatment. The book introduces key concepts in the study of cancer, explaining how cancers develop, covering a variety of approaches to their diagnosis and treatment. It also includes discussions of new approaches to preventing cancers, screening programmes, and innovations in diagnosis that draw on AI. These provide insights into current developments in cancer research and show how they benefit patients.
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Cancer diagnosis and screening
This chapter focuses on cancer diagnosis and screening. It explains that cancer is usually treatable if found early enough, so warning signs and symptoms should not be ignored. Population screening for common cancers is an important and alternative way of detecting cancer. Diagnosis depends heavily on molecular characteristics of a tumour as these allow medical professionals to determine the optimum type of therapy needed. They also give information on predicting the development of the disease (prognosis). The chapter highlights that accurate diagnosis is necessary for optimal patient management. In cancer, it is not easy to get the perfect screening test since under-diagnosis can cost lives, while over-diagnosis causes unnecessary anxiety and intrusive treatment.
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The cancer genome: mutations versus repair
This chapter looks at the structures of genes and describes the mutations that occur during carcinogenesis. It argues that changes in the nucleotide sequence of DNA — called mutations — are crucial for acquiring the hallmarks of cancer and have been labeled an enabling characteristic. The chapter then investigates how, on the one hand, mutations in DNA occur as a consequence of exposure to carcinogens and, on the other hand, examine the DNA repair systems that are in place to maintain the integrity of the genome and suppress tumorigenesis. The chapter then shifts to define the genetic information, coded within DNA, and the role of the accumulation of mutations. Ultimately, the chapter concludes with a discussion of conventional chemotherapies and a new class of drugs that target DNA repair pathways. It also studies the recent findings from advances in sequencing technology and imaging.
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Cancer stem cells and the regulation of self-renewal and differentiation pathways: focus on colon cancer and leukemias
This chapter begins with an overview of the process of differentiation during development and in the adult. It outlines the characteristics of cells at different degrees of differentiation and discusses their relationship to cancer. The chapter also covers the review of the “cancer stem cell model” that states that subpopulations of cells with stem cell properties initiate and maintain the cancer phenotype. These cells often reside in distinct microenvironments in tumors, called stem cell niches. Signals from the stem cell niche dictate stem cell fate and behaviour. The chapter then reviews the molecular mechanisms that underlie the regulation of self-renewal and examines specific mutations in these pathways that can lead to cancer. Finally, the chapter elaborates on the new cancer therapeutics designed to target aspects of self-renewal and differentiation pathways.
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Cancer—a multitude of diseases
This chapter examines the notion of cancer as a multitude of diseases. It shows that benign tumours are not classified as cancer because they do not metastasize and spread around the body to other organs. Prognosis depends on the type, grade, and stage of a tumour and its response to treatment. The chapter explains that cancer is a multistep process that requires multiple genetic and epigenetic changes to occur in cells that also need time to develop. It then provides an overview of the hallmarks of cancer, citing that different cancers share several common traits despite being a diverse set of diseases.
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Catalytic RNAs
This chapter looks at how RNA molecules catalyse chemical reactions, a domain which was previously thought to be reserved only for proteins. It clarifies that RNA has a more limited set of functional groups for building catalysts, which are confined to just four different nucleotides: A, C, G, and U. It also highlights the ability of RNA molecules to form structures which also enables the assembly of RNA active sites. The chapter outlines the important function of metal ions in ribozymes, which includes helping RNA structures form and balance the strong negative charge in ribozyme active sites that result from high densities of RNA strands. It also mentions that the purine and pyrimidine bases of RNA have NH groups that can potentially act as hydrogen donors or acceptors in acid-base catalysis.
Chapter
The cell cycle
Jorrit M. Enserink, Helene Knævelsrud, and Joseph M. Robertson
This chapter highlights the basic mechanism and regulation of the cell cycle. It defines the cell cycle as the ordered series of events that lead to duplication of the chromosomes and other cellular components, followed by cell division. The chapter emphasizes that the cell cycle is made up of four stages: G1, S phase, G2, and M phase. G1, S phase, and G2 constitute the cycle phase called interphase. The genetic material of a cell is replicated in S phase (DNA synthesis), and M phase involves partitioning of the cell and genome. The chapter then introduces the cyclins and cyclin-dependent kinases (CDKs), the main players in the cell cycle. It also investigates the molecular mechanisms involved in the regulation of the cell cycle. Next, it describes specific mutations that affect the cell cycle and play a role in carcinogenesis. It also discusses therapeutic strategies that target molecules of the cell cycle.
Chapter
The cell cycle
This chapter focuses on the cell cycle, which encompasses a series of highly coordinated processes that ensure cell duplication in a precise and timely manner. In eukaryotes, cyclin–Cdks (cyclin-dependent kinases) promote not only the processes that take place during a particular cell cycle phase, but also how cyclin–Cdks activate the next phase and extinguish the previous one. Regulatory pathways called checkpoints are superimposed on the cyclin–Cdk machinery and inhibit cell cycle progression in the presence of damage or certain types of errors in the cell. The multiple levels of regulation illustrate the importance of carrying out cell cycle processes with utmost accuracy. Indeed, failure to do so can result in cancer. Bacteria are more diverse in terms of their cell cycle schemes. The major regulatory steps in many bacteria are initiation of DNA replication, which is often coupled to chromosome segregation, and cell division.
Chapter
The cell cycle, cell division, cell death, and cancer
This chapter looks at the eukaryotic cell cycle. This is divided into several phases: the first gap phase (G1), the DNA synthesis phase (S), the second gap phase (G2), and the mitotic or cell division phase (M). The chapter reviews progression through the phases. This depends on the synthesis of cyclin proteins specific for different phases. At the end of each phase the cyclins are destroyed by proteolysis. The cyclins are required to activate different cyclin-dependent protein kinases (Cdks) and determine which substrates a given kinase works on in each phase of the cycle. The chapter refers to the cyclin synthesis in G1, stating that it requires the receipt by the cell of a mitogenic signal from a growth factor or cytokine. After entering M phase, a further check is made to establish that all of the chromosomes are correctly placed on the mitotic spindle.
