This chapter reviews the general functions of hormones, their chemical nature, mechanism of action, and regulation, before focusing on disorders of hormones released by the pituitary gland. Hormones are chemical messengers produced by endocrine glands that circulate in the blood and act on target cells via receptors. The pituitary gland is influenced by release of peptides from the hypothalamus and also releases peptide hormones itself, which influence release of hormones from other endocrine glands located in the thyroid, adrenals, and gonads. The chapter then differentiates between hyperfunction and hypofunction of the anterior pituitary. Posterior pituitary dysfunction can result in low antidiuretic hormone (ADH) secretion, which presents clinically as cranial diabetes insipidus. Release of hormones from the pituitary gland can be investigated by measuring the concentration of single hormones in serum or by dynamic function testing.
Abnormal pituitary function
Abnormalities of lipid metabolism
This chapter explores the role of lipids in the development of cardiovascular disease. Different types of lipids occur in the body and include fatty acids, triacylglycerol, phospholipids, and cholesterol. Lipids are insoluble in water and associate with apoproteins in the blood to give lipoproteins, and this is the form in which they are transported in the circulation. Lipid disorders can either be genetic in origin or secondary to other diseases, drug treatment, or defective nutrition. The chapter then looks at hypercholesterolaemia, hypocholesterolaemia, and hypertriglyceridaemia. Deposition of lipids in arterial walls and the subsequent formation of an atheroma are key features of atherogenesis and coronary heart disease. Management of hyperlipidaemia involves using a combination of lifestyle changes aimed at reducing risk factors and the use of lipid-lowering drugs such as statins.
This chapter assesses homeostasis of H+ions, the causes and consequences of acid-base disorders, and their laboratory investigation. The physiological control of H+ concentration is maintained by three interrelated mechanisms: buffering systems, the respiratory system, and the renal system. Intracellular and extracellular buffering systems, such as bicarbonate and haemoglobin, provide an immediate, but limited, response to pH changes. The respiratory system, which can be activated almost immediately, controls PCO2 by changing alveolar ventilation. The renal system regulates [HCO3 -] and is the slowest to respond. The physiological response to an acid-base disturbance, which limits the change in H+ concentration, is referred to as compensation. The chapter then looks at acidosis, alkalosis, and mixed acid-base disorders. Acid-base data can be interpreted in a systematic manner, from laboratory results, by examining pH status, PCO2 results, and the compensatory response by HCO3 -.
Acids, bases, and buffer solutions: life in an aqueous environment
This chapter discusses the key properties of aqueous environments that are pivotal to biochemical reactions happening correctly. It examines the behaviour of acids and bases—why they are important to the chemistry of life, what distinguishes them from other compounds, and how their behaviour is kept in check. The chapter outlines the Brønsted–Lowry definitions of acid and base: namely, that an acid is a hydrogen ion donor, while a base is a hydrogen ion acceptor. The chapter then looks at conjugate acid–base pairs, before considering the strength of acids and bases. The acid dissociation constant provides a measure of the extent to which an acid dissociates in aqueous solution. The chapter also studies the ion product of water, the pH scale, and neutralization reactions. It also discusses the behaviour of acids and bases in biological systems before turning to buffer solutions, and their importance to biology.
This chapter evaluates the morphology, development, functions, and regulation of the adrenal glands, before looking at adrenal disorders. The adrenal glands have an outer cortical region and an inner medulla with different functions. The adrenal cortex produces aldosterone, cortisol, and dehydroepiandrosterone sulfate (DHEAS); the medulla produces adrenaline and noradrenaline. In the newborn infant, metabolites of DHEAS are also produced by the fetal adrenal gland and can interfere with some methods. The execution and interpretation of laboratory hormone tests need special consideration, particularly with regard to assay specificity, reference ranges for age, development, and in some cases body size. The chapter then considers immunoassays, steroid hormone assays, and the analysis of the profile of urinary steroids by gas chromatography with mass spectrometry. A number of disorders of the adrenal glands are due to genetic defects in enzymes or neoplasms. Once recognized, these disorders are treatable by surgery and/or hormone replacement therapy.
Aerobic Metabolism I: The Citric Acid Cycle
This chapter discusses modern aerobic organisms that transduce the chemical bond energy of food molecules into the bond energy of adenosine triphosphate (ATP). It examines how aerobic organisms perform this feat where oxygen is used as the terminal acceptor of the electrons extracted from food molecules. The capacity to use oxygen to oxidise nutrients, such as glucose and fatty acids, yields a substantially greater amount of energy than does fermentation. The chapter recounts the accumulation of atmospheric O2 on Earth about 2 billion years ago, when existing organisms were confronted with a serious problem: molecular oxygen forms toxic oxygen ions and peroxides called reactive oxygen species (ROS). ROS react with and damage or destroy biomolecules. Consequently, exposure to O2 acted as a severe selection pressure.
Aerobic Metabolism II: Electron Transport and Oxidative Phosphorylation
This chapter analyses how the aerobic lifestyle depends on the large quantities of energy made possible by oxygen, which is also required directly or indirectly for 1000 biochemical reactions that cannot occur under anaerobic conditions. It cites research efforts which have revealed that aerobic organisms have evolved an array of mechanisms that provide protection from the toxic by-products of oxygen metabolism. Many enzymes and antioxidant molecules prevent most oxidative cell damage. The chapter describes oxygen metabolites that are now known to contribute to an array of human disorders that include cancer and heart and neurological diseases. Oxygen has several properties that, when combined, have made possible a highly favourable mechanism for extracting energy from organic molecules.
An alternative pathway of glucose oxidation: the pentose phosphate pathway
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.
Amino Acids, Peptides, and Proteins
This chapter discusses proteins as molecular tools. These perform an astonishing variety of functions. In addition to serving as structural materials in all living organisms, proteins are involved in diverse functions as catalysis, metabolic regulation, transport, and defence. Proteins are composed of one or more polypeptides, unbranched polymers of 20 different amino acids. The chapter looks at the genomes of organisms which specify the amino acid sequences of thousands or tens of thousands of proteins. It describes proteins as a diverse group of macromolecules that are directly related to the combinatorial possibilities of the 20 amino acid monomers. Amino acids can be theoretically linked to form protein molecules in any imaginable size or sequence.
Atoms: the foundations of life
This chapter discusses atoms and their components, looking at protons, electrons, and neutrons. It begins by defining chemical elements, and studies the periodic table, which displays all the known chemical elements in order of ascending atomic number. Periodicity is the gradual change in chemical property from element to element as one moves across a period, and the similarity of chemical and physical properties exhibited by elements within the same group. The chapter then explores atomic composition and structure, distinguishing between the Bohr model and the quantum mechanical model of atomic structure. The chapter discusses ions, which are atoms that have either gained or lost one or more electrons, and the ionization energy, which describes the amount of energy required to remove an electron from an atom. It also explains how isotopes are atoms of the same element that contain different numbers of neutrons. Finally, the chapter considers the electronic configuration of atoms, valence shells and valence electrons, and electron excitation.
This chapter examines automation in clinical biochemistry. Two main types of instrument, the general chemistry analyser and the immunochemistry analyser, predominate in clinical biochemistry laboratories, but a wide range of hybrid and combination analysers are available. Key steps in an automated analytical process are often common to many instruments, although there is often significant variation in application, design, and operation. Consolidation of most of the biochemical test repertoire is now possible on a single system that comprises a set of integrated analysers. Ultimately, total laboratory automation automates three phases of laboratory testing, namely preanalytical, analytical, and postanalytical, in a continuous process. A complex automation system requires extensive monitoring and careful management to achieve consistent and optimal efficiency.
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.
Biochemical investigations and quality control
This chapter discusses the roles of the clinical biochemistry laboratory in the diagnosis, treatment, monitoring, and prognosis of disease states. The equipment used to analyse clinical samples is often complex and large laboratories will produce many thousands of results daily. However, advances made in automation, robotics, and computing have made it possible to cope with ever-increasing workloads, even when the numbers of staff are reduced. Specialist tests are often performed on clinical samples at regional centres where the required expertise is available and to reduce duplication of expensive equipment. In contrast, point-of-care testing (POCT) is increasing and although presenting numerous benefits, it presents a new challenge to the clinical laboratory. Quality control is essential for all assays and when utilized properly gives confidence to the laboratory staff and to users of the service with regard to precision and accuracy of all the tests performed.
Patrick Twomey and William Simpson
This chapter focuses on biochemical nutrition, looking at different types of nutrients (macronutrients, organic micronutrients, and inorganic micronutrients) and the consequences of their deficiencies and excesses. Clinically, effective nutritional care requires assessment and monitoring of nutritional status and an understanding of the effects of illness, in order to ensure appropriate provision of nutrients to patients. Prolonged nutritional imbalance leads to malnutrition. The laboratory has an important role in assessment and monitoring of specific nutrients, but results of these analyses must be interpreted appropriately, with special regard to the acute phase response (APR). Measurements are most often performed in serum or urine because of the relative analytical ease, but these measurements can only offer limited information; analyses in the laboratory rarely provide information on whole body nutrient status. The chapter then considers disordered eating patterns and nutritional intervention.
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.
Trudy McKee and James R. McKee
Biochemistry begins with an introduction to the topic. Discussions covered include living cells, the importance of water to life, energy, and amino acids, peptides, and proteins. The book also contains chapters on carbohydrates, carbohydrate metabolism, aerobic metabolism, and lipids and membranes. The text goes on to examine photosynthesis, nitrogen metabolism, nucleic acids, and genes. Finally, it looks at protein synthesis.
Richard Bowater, Laura Bowater, and Tom Husband
Biochemistry introduces this topic with an examination of carbohydrates, asking why we need them in our lives. It then looks at the building blocks of a cell, namely, lipids and proteins. Nucleotides and nucleic acids are the next topic to be covered. The text moves on to consider metabolism. It asks what it means and how energy is transformed. Other questions asked include: how is a metabolic balance maintained? How can we solve the problems of the future with natural products? Finally, the text looks at bioenergy and the environment.
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.
Biochemistry: An Introduction
This chapter provides a background to the science of biochemistry, which, since the nineteenth century, has developed sophisticated intellectual and laboratory tools for the investigation of living processes. The chapter explores the capacity to understand and appreciate the significance of this phenomenon. This understanding begins with a thorough knowledge of biochemical principles. The chapter focuses on the structure and functions of the most important biomolecules and the major biochemical processes that sustain life. It describes the concepts of modern experimental biochemistry and investigates strategy used to improve the understanding of living organisms as integrated systems rather than collections of isolated components and chemical reactions.
Biological macromolecules: the infrastructure of life
This chapter studies some of the key biological macromolecules that make life happen: amino acids and proteins, nucleic acids, carbohydrates, and lipids. Amino acids join together to form polymers named polypeptides. The structure of proteins is built up over four levels of hierarchy: primary, secondary, tertiary, and quaternary. Protein structure is stabilized by both non-covalent interactions (including hydrogen bonds and hydrophobic interactions) and covalent bonding, including disulfide bonds. The chapter also describes the two key natural nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are polymers of nucleotides. The chapter then considers the three main classes of carbohydrate (sugar)—monosaccharides, disaccharides, and polysaccharides. It also looks at the three most important types of lipid: steroids, triacylglycerols, and the glycerophospholipids.