BIOCHEMISTRY AND THE CELL

Virchow, who was largely responsible for the acceptance of the cell theory, developed microscopy of cells from normal and diseased tissues as a major tool (histopathology) in the clinical armory. He believed the vital functions of the cell, growth, maintenance, and multiplication were discharged by its nucleus the specialised, distinguishing functions were made possible by the extranuclear constituents. In a Sunday evening lecture in Edinburgh in 1868, On the Physical Basis of Life , Thomas Huxley described cells as protoplasmic masses usually 

By the early years of this century the cell was generally recognized as the smallest unit capable of independent life. Gowland Hopkins in 1913 first clearly formulated ideas which would be the death of protoplasm. Life is the expression of a particular dynamic equilibrium which obtains in polyphasic systems. .. life is a property of the cell as a whole.  

To obtain tissue preparations whose constituents were maintained as closely as possible to their state in vivo, the material had to be fixed, i.e. the enzymes inactivated so that cell structures were instantaneously preserved, an almost unattainable ideal. Formalin was the favored fixative, but others (e.g. picric acid), were also employed. Different methods of fixation caused sections to have different appearances. Further artifacts were introduced because of the need to dehydrate the preparations so that they could be stained by dyes, many of which were lipid-soluble organic molecules. Paraffin wax was used to impregnate the fixed, dehydrated material. The block of tissue was then sectioned, originally by hand with a cut-throat razor, and later by a mechanical microtome. The sections were stained and mounted in balsam for examination. Hematoxylin (basophilic) and eosin (acidophilic) (H and E staining) were the commonest stains, giving blue nuclei and pink cytoplasm. Eosinophils in the blood were recognized in this way. 

A suitable method for this was introduced by Caspersson (mid-1920s-ca. 1940) who designed and successfully exploited UV microscopy so that the extent of the absorbtion could be determined quantitatively. Selective hydrolysis by RNAase or DNAase was used so that the DNA content of the cell could be estimated. The procedure still required reproducible preparation of sections to allow light to be transmitted and the enzymes to get access to the nucleic acids. 

UV microscopes were sophisticated to use and very expensive. A number of workers, notably Pollister and Swift, devised cytophoto-metric procedures with visible light, using Feulgen staining calibrated against UV microphotometry. The DNA content of the nucleus could then be measured relative to that in other cells. Lymphocytes were used as a standard. 

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CONTENTS Acknowledgments, Margery G. Ord and Lloyd A. Stocken. Introduction. Biochemistry Before 1900. Early Metabolic Studies Energy Needs and the Composition of the Diet. Carbohydrate Utilization Glycolysis and Related Activities. Aspects of Carbohydrate Oxidation, Electron Transfer, and Oxidative Phosphorylation. Amino Acid Catabolism in Animals. The Utilization of Fatty Acids. The Impact of Isotopes 1925-1965. Biochemistry and the Cell. Concepts of protein Structure and Function. Chronological Summary of Main Events Up to ca. 1960. Principal Metabolic Pathways. Index. 

The intracellular environment of eukaryote cells can be subdivided into many regions, including the organelles, nucleus, cytoplasm and the cell periphery. Thus solutes must be delivered to the right intracellular compartment at the correct time to efficiently serve cellular biochemistry. Uncharged solutes such as glucose presumably diffuse across the cell, and the traditional view held until recently was that the major electrolytes, such as Na+,K+,CF and Mg2+, also move around the cell by simple diffusion to eventually arrive at the relevant subcellular compartment by chance. 

The role of many hormones, and particularly those discussed in this chapter, is to change the flux through a biochemical pathway or process. In order to identify the mechanism by which the hormone affects the biochemistry in the cell, it is necessary to know or to predict which... 

Post RM, Chuang D-M Mechanism of action of lithium comparison and contrast with carbamazepine, in Lithium and the Cell Pharmacology and Biochemistry. Edited by Birch NJ. London, Academic Press, 1991, pp 199-241 Post RM, Weiss SRB The neurobiology of treatment-resistant mood disorders, in Psychopharmacology The Fourth Generation of Progress. Edited by Bloom FE, Kupfer DJ. New York, Raven, 1995... 

In this introductory chapter, then, we describe (briefly ) the cellular, chemical, physical (thermodynamic), and genetic backgrounds to biochemistry and the overarching principle of evolution—the development over generations of the properties of living cells. As you read through the book, you may find it helpful to refer back to this chapter at intervals to refresh your memory of this background material. 

Mather, I. H. and Keenan, T. W. 1983. Function of endomembranes and the cell surface in the secretion of organic milk constituents. In Biochemistry of Lactation. T. B. Mepham (Editor). Elsevier/North-Holland, Amsterdam, pp. 231-283. 

Whilst such a formula may be meaningless in terms of the biochemistry of the cell, and its accuracy should be viewed with reference to Table 5.9, it does serve a useful purpose when considering the stoichiometry of the microbial activity. 

Membrane proteins carry out a wide range of critical functions in cells, and they include passive and active transporters, ion chamiels, many classes of receptors, cellular toxins, proteins involved in membrane trafficking, and the enzymes that facilitate electron transport and oxidative phosphorylation. For example, the voltage-gated ion channels that facilitate the passive diffusion of sodium and potassium across the axonal membrane are responsible for the formation of an action potential. Active transport proteins establish ion gradients and are necessary for the uptake of nutrients into cells. Soluble hormones bind to membrane receptors, which then regulate the internal biochemistry of the cell. 

The Affective Disorders Manic Depressive Psychoses Lithium in the Affective Disorders A. Side Effects Chemistry Isotopes of Lithium Inorganic Biochemistry Mechanisms of Action Lithium and the Phosphoinositide Signaling System Lithium and the Cell Membrane A. Sodium-Lithium Exchange Anion Exchange Leak... 

In the past, compounds from nature often opened up completely new therapeutic approaches. Moreover, natural compounds substantially contributed to identify and understand novel biochemical pathways in vitro and in vivo, and consequently proved to make available not only valuable drugs but also essential tools in biochemistry, and molecular cell biology. It is worth while studying exhaustively the molecular basis of biological phenomena of new and/or unusual chemical structures from nature. Numerous examples from medicine impressively demonstrate the innovative potential of natural products and their impact on progress in drug discovery and development as discussed below. 

But the differences, as we shall see, are not nearly as great as the similarities, and for much of this book we shall be describing the biochemistry of an ideal or typical animal cell, which might be that of most organs of most species. Only very much later will we come to consider in any detail how the biochemistry of the cells of different organs and species actually differ from one another. 

A complete statement of the biochemistry of the cell must not only be able to list what enzymes are present in the system, but where they are located within the cell, whether they are maximally active or lying dormant for lack of substrate or cofactors, and how their activity relates to that of all the other cellular components. The reasons for this will become more apparent when we turn to consider in due course the control of metabolism (Chapter 11). For the moment we should emphasize that each of the methods... 

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