Further Reading:

General:

Anfinsen, C.B. (1973) Principles that govern the folding of protein chains. Science 181 223-230.

  The author reviews his classic work on ribonuclease.

Branden, C. & Tooze, J. (1991) Introduction to Protein Structure, Garand Publishing, Inc., New York.

Creighton, T.E. (1993) Proteins: Structures and Molecular Properties, 2^nd edn, W>H. Freeman and Company, New York.

  A comprehensive and authoritative source.

Evolution of Catalytic Function. (1987) Cold Spring Harb. Symp. Quant. Biol. 52.

  A source of excellent articles on many topics, including protein structure, folding, and function.

Kendrew, J.C.(1961) The three-dimensional structure or a protein molecule. Sci. Am. 205 (December), 96-111.

  Describes how the structure of myoglobin was determined and what was learned from it.

Richardson, J.S.(1981) The anatomy and taxonomy of protein structure. Adv. Prot. Chem. 34, 167-339.

  An outstanding summary of protein structural patterns and principles; the author originated the very useful “ribbon’ representations of protein structure.

Secondary, Tertiary, and Quaternary Structure:

Brenner, S.E., Chothia, C., & Hubbard, T.J.P.(1997) Population statistics of protein structures: lessons from structural classifications. Curr. Opin. Struct. Biol. 7, 369-376.

Chothia, C., Hubbard, T., Brenner, S., Barns, H., & Murzin, A. (1997) Protein folds in the all-βand all-α classes. Annu. Rev. Physiol. Biomol. Struct. 26, 597-627.

Fuchs, E. & Cleveland, D. W. (1998) A structural scaffolding of intermediate filaments in health and disease. Science 279, 514-519.

McPherson, A. (1989) Macromolecular crystals. Sci. Am. 260 (March), 62-69.

  Describes how macromolecules such as proteins are crystallized.

Prockop, D. J. & Kivirikko, K.I. (1995) Collagens, molecular biology, diseases, and potentials for therapy. Annu. Rev. Biochem. 64, 403-434.

Shoeman, R.L. & Traub, P. (1993) Assembly of intermediate filaments. Bioessays 15,605-611.

Protein Denaturation and Folding:

Aurora, R., Creamer, T.P., Srinivasan, R., & Rose, G.D.(1997) Local interactions in protein folding: lessons from the α-helix. J. Biol. Chem. 272, 1413-1416.

Baldwin, R. L. (1994) Matching speed and stability. Nature 369, 183-184.

Creighton T. E., Darby, N.J., & Kemmink, J. (1996) The roles of partly folded intermediates in protein folding. FASEB J. 10, 110-118.

Dill, K.A. & Chan, H.S. (1997) From Levinthal to pathways to funnels. Nat. Struct. Biol. 4, 10-19.

 Johnson, J.L.& Craig, E.A. (1997) Protein folding in vivo: unraveling complex pathways. Cell 90, 201-204.

Netzer, W. J. & Hartl, F.U. (1998) Protein folding in the cytosol: chaperonin-dependent and independent mechanises. Trends Biochem. Sci. 23, 68-73.

Prusiner, S.B., Scott, M.R., DeArmond, S.J., & Cohen, F.E. (1998) Prion protein biology. Cell 93, 337-348.

Richardson, A., Landry, S.J., & Georgopolous, C. (1998) The ins and outs of a molecular chaperone machine. Trrends Biochem. Sci 23, 138-143.

Ruddon, R.R> & Bedows, E. (1997) Assisted protein folding. J. Biol. Chem. 272, 3125-3128.

Thomas, P.J., Qu, B-H., & Pederson, P.L. (1995) Defective protein folding as a basis of human disease. Trends Biochem. Sci. 20, 456-459.

Chapter 4

Further Reading:

General:

Denny, M.W. (1993)Air and Water: The Biology and Physics of Life’s Media, Princeton University Press, Princeton, NJ.

  A wonderful investigation of the biological relevance of the properties of water.

Eisenberg, D. & Kauzmann, W. (1969) The Structure and Properties of Water, Oxford University Press, New York.

  An advance d treatment of the physical chemistry of water.

Franks, F.& Mathias, S. F. (eds) (1982) Biophysics of Water, John Wiley & Sons, Inc., Ynew York.

  A large collection of papers on the structure of pure water and of the cytoplasm.

Gerstein M. & Levitt, M. (1998) Simulating water and the molecules of life. Sci. Am. 279 (November), 100-105.

  A well-illustrated description of the use of computer simulation to study the biologically important association of water with proteins and nucleic acids.

Groneborn, A. & Clore, M. (1997) Water in and around proteins. The Biochemist 19 (3), 18-21

  A brief discussion of protein-bound water as detected by crystallography and NMR.

Kornblatt, J. & Kornblatt, J. (1997) The role of water in recognition and catalysis by enzymes. The Biochemist 19 (3), 14-17.

  A short, useful summary of the ways in which bound water influences the structure and activity of proteins.

Kuntz, I.D. & Zipp, A. (1977) Water in biological systems. N. Engl. J. Med. 297, 262-266.

  A brief review of the physical state of cytosolic water and its interactions with dissolved biomolecules.

Ladbury, J. (1996) Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug design. Chem. Biol. 3, 973-980.

Stillinger, F.H. (1980) Water revisited. Science 209, 451-457.

  A short review of the physical structure of water, including the importance of hydrogen bonding and the nature of hydrophobic interactions.

Westhof, E. (ed.) (1993) Water and Biological Macromolecules, CRC Press, Inc., Boca Ration, FL.

  Fourteen chapters, each by a different author, cover (at an advanced level) the structure of water and its interactions with preoteins, nucleic acids, polysaccharides, and lipids.

Wiggins, P.M. (1990) Role of water in some biological processes. Microbiol. Rev. 54, 432-449.

  A review of water in biology, including discussion of the physical structure of liquid water, its interaction with biomolecules, and the state of water in living cells.

Weak interactions in Aqueous Systems:

Fersht, A. R. (1987) The hydrogen bond in molecular recognition. Trends Biochem. Sci. 12, 301-304.

  A clear, brief, quantitative discussion of the contribution of hydrogen bonding to molecular recognition and enzyme catalysis.

Frieden, E. (1975) Non-covalent interactions: key to biological flexibility and specificity. J. Chem. Educ. 52, 754-761.

  Review of the four kinds of weak interactions that stabilize macromolecules and confer biological specificirty, with clear examples.

Jeffrey, G. A. (1997) An Introduction to Hydrogen Bonding, Oxford University Press, New York.

  A detailed and advanced discussion of the structure and properties of hydrogen bonds including those in water and biomolecules.

Schwabe, J.W.R. (1997) The role of water in protein-DNA interactions. Curr. Opin. Struct. Biol.7, 126-134.

  Examines the important role of water in both the specificity and affinity of protein-DNA interactions.

Tanford, C. (1978) The hydrophobic effect and the organization of living matter. Science 200m 1012-1018.

  A review of the chemical and energetic basis for hydrophobic interactions between biomolecules in aqueous solutions.

Weak Acid, Weak Bases, and Buffers:

Problems for Practice

Segel, I.H. (1976) Biochemical Calculations, 2^nd edn, John Wiley & Sons, Inc., New York.

Chapter 2:  

P21

The upper limit of cell size is probably set by the rate of diffusion of solute molecules in aqueous systems. A bacterial cell that depends upon oxygen-consuming reactions for energy production (an aerobic cell) must obtain molecular oxygen from the surrounding medium by diffusion through its plasma membrane. The cell is so small, and the ratio of its surface area to its volume is so large, that every part of its cytoplasm is easily reached by O2 diffusing into the cell. As cell size increases, however, surface-to-volume ratio decreases, until metabolism consumes O2 faster than diffusion can supply it. Aerobic metabolism thus becomes impossible as cell size increases beyond a certain point, placing a theoretical upper limit on the size of the aerobic cell.

        P31

Phagocytosis is a special case of endocytosis in which the material carried into the cell (within a phagosome) is particulate, such as a cell fragment or even another, smaller cell.

        P47

The outbreaks of Hantavirus in the southwestern United States in 1993 and of the Ebola virus in central Africa in 1995 illustrate the extreme pathogenicity of some viruses. Both viruses produce diseases with rapid courses and high mortality.

        P48  Summary

Cells, the structural and functional units of living organisms, are of microscopic dimensions. Their small size, combined with convolutions of their surfaces, results in high surface-to-volume ratios, facilitating the diffusion of fuels, nutrients, and waste products between the cell and its surroundings. All cells share certain features: DNA containing the genetic information, ribosomes, and a plasma membrane that surrounds the cytoplasm in eukaryotes the genetic material is surrounded by a nuclear envelope; prokaryotes have no such membrane.

The plasma membrane is a tough, flexible permeability barrier, which contains numerous transporters as well as receptors for a variety of extracellular signals. The cytoplasm of eukaryotic cells consists of the cytosol and organelles. The cytosol is a concentrated solution of proteins, RNA, metabolic intermediates and cofactors, and inorganic ions. Ribosomes are supramolecular complexes on which protein synthesis occurs; bacterial ribosomes are slightly smaller than those of eukaryotic cells, but are similar in structure and function.

Certain organisms, tissues, and cells offer advantages for biochemical studies. E. coli and yeast can be cultured in large quantities, have short generation times, and are especially amenable to genetic manipulation. The specialized functions of liver, muscle, and fat tissue, and of erythrocytes, make them attractive ofr the study of specific processes. The first living cells were prokaryotic and anaerobic; they arose about 3.5 billion years ago, when the atmosphere was devoid of oxygen. With the passage of time, biological evolution led to cells capable of photosynthesis, with O2 as a byproduct. As O2 accumulated, prokaryotic cells capable of the aerobic oxidation of fuels evolved. The two major groups of prokaryotes, eubacteria and archaebacteria, diverged early in evolution. The cell envelope of some types of bacteria includes layers outside the plasma membrane that provide rigidity of protection. Some bacteria have flagella for propulsion. The cytoplasm of bacteria has no membrane-bounded organelles but does contain ribosomes and granules of stored fuels, as well as a nucleoid that contains the cell’s DNA. Some photosynthetic bacteria have extensive intracellular membranes that contain light-capturing pigments.

About 1.5 billion years ago, eukaryotic cells emerged. They were larger than prokaryotes and their genetic material was more complex. These early cells established symbiotic relationships with prokaryotes that lived in their cytoplasm; modern mitochondria and chloroplasts are derived form these early endosymbionts. Mitochondria and chloroplasts are intracellular organelles surrounded by a double membrane. They are the principal sites of ATP synthesis in eukaryotic, aerobic cells. Chloroplasts are found only in photosynthetic organisms, but mitochondria are ubiquitous among eukaryotes.

Modern eukaryotic cells have a complex system of intracellular membranes. This endomembrane system consists of the nuclear envelope, rough and smooth endoplasmic reticulum, the Golgi complex, transport vesicles, lysosomes, and endosomes. Proteins synthesized on ribosomes bound to the rough endoplasmic reticulum pass into the endomembrane system, traveling through the Golgi complex on their way to organelles or to the cell surface, where they are secreted by exocytosis. Endocytosis brings extracellular materials into the cell, where they can be digested by degradative enzymes in the lysosomes. In plants, the central vacuole is the site of degradative processes; it also serves as a storage depot for pigments and other metabolic products and maintains cell turgor.

The genetic material in eukaryotic cells is organized into chromosomes, highly ordered complexes of DNA and histone proteins. Before cell division( cytokinesis), each chromosome is replicated and the duplicate chromosomes are separated by the process of mitosis.

The cytoskeleton is an intracellular meshwork of actin filaments, microtubules, and intermediate filaments of several types. The cytoskeleton confers shape on the cell, and reorganization of cytoskeletal filaments results in the shape changes accompanying amoeboid movement and cell division. Intracellular organelles move along filaments of the cytoskeleton, propelled by proteins such as kinesin, cytoplasmic dynein, and myosin, using the energy of ATP. Biochemists use differential centrifugation and isopycnic centrifugation to isolate subcellular components for study.

In multicellular organisms, there is a division of epithelial cells in animals can be joined to each other mechanically by tight junctions and desmosomes; communication channels are provided by gap junctions (in animals) and plasmodesmata (in plants). Viruses are parasites of living cells, capable of subverting the cellular machinery for their own replication. They infect animal,plant, and bacterial cells and are responsible for a variety of serious human diseases.

Further Reading:

General:

Alberts, B., bray, D., Lewis, J., Raff, M..,Roberts, K., & Watson, J.D.(1994)Molecular Biology of the Cell, 3^rd edn, Garland Publishing, Inc., New York.

  A superb textbook on cell structure and function, covering the topics considered in this chapter, and a useful reference for many of the following chapters.

Becker, W.M. ,Reece, J.M., & Peonie, M.F.(1995)

The World of the Cell, 3^rd edn, the Benjamin /Cummings Publishing Company, Redwood City, CA.

  An excellent introductory textbook of cell biology

Lodish, H., Baltimore, D., Berk, A., Zipursky, S.L., Matsudaira, P., & Darnell, J.(1995)

  Molecular Cell Biology, 3^rd edn, Scientific American Books, Inc., New York.

  Like the book by Alberts and coauthors, a superb text useful for this and later chapters.

Margulis, L. (1996) Archaeal-eubacterial mergers in the origin of Eukarya: phylogenetic classification of life. Proc. Natl. Acad. Sci. USA93, 1071-1076

  The arguments for dividing all living creatures into five kingdoms: Monera, Protoctista, Fungi, Animalia, Plantae.

Structure of Cells, Organelles, and Cytoskeleton:

Block, S.M. (1998) Leading the procession: new insights into kinesin motors. J. Cell Biol. 140, 1281-1284.

Fawcett, D.W. & Jensh, R.O. (eds) (1997) Bloom and Fawcett: Concise Histology, Chapman& Hall, London.

  A well-illustrated textbook of cell structure at the microscopic level.

Frontiers in Cell Biology: The Cytoskeleton. (1998)

Science 279, 509-533

  This special issue includes the following papers:

Hall, A., Rho GTPases and the actin cytoskeleton (pp. 509-514); Fuchs, E.& Cleveland, D.W.,A structural scaffolding of intermediate filaments in health and disease (pp. 514-519); Hirokawa, N., Kinesin and dynein superfamily proteins and the mechanism of organelle transport (pp. 519-526); Mermall, V., Post, P.L., & Mooseker, M.S., Unconventional myosins in cell movement, membrane traffic, and signal transduction (pp. 527-533).

Gelfand, V. & Bershadsky, A.D. (1991) Microtubule dynamics: mechanism, regulation, and function. Annu. Rev. Cell Biol. 7, 93-116.

Organization of the Cytoplasm. (1981) Cold Spring Harb. Symp. Quant. Biol. 46.

  More than 90 excellent papers on microtubules, microfilaments, and intermediate filaments and their biological roles.

Rothman, J.E. & Orci, L. (1996) Budding vesicles in living cells. Sci. Am. 274 (March), 70-75.

  A clear description of the dynamics of the endomembrane system.

Schroer, T. A. & Sheetz, M.P. (1991) Functions of microtubule-based motors. Annu. Rev. Physiol 53, 629-652.

Spudich, J.A. (1996) Structure-function analysis of the motor domain of myosin. Annu. Rev. Cell Dev. Biol. 12, 543-573.

Takai, Y., Sasaki, T., Tanaka, K., & Nakanishi, H. (1995) Tho as a regulator of the cytoskeleton. Trends Biochem. Sci. 20, 227-231.

  Short review of the evidence that the small GTP-binding protein Rho controls the assembly and structure of actin filaments.

Vale, R.D. & Fletterick, R.J. (1997) The design plan of kinesin motors. Annu. Rev. Cell Dev. Biol. 13, 745-777.

  Detailed review of the structure and mechanism of the molecular motors in the kinesin superfamily.

Chapter 1

Further Reading:

Asimov,I.(1962) Life and Energy: An Exploration of the Physical and Chemical Basis of Modern Biology, Doubleday & Co., Inc., New York.

  An engaging account of the role of energy transformations in biology, written for the intelligent layperson by a biochemist and superb writer.

Blum, H.F. (1968) Time’s Arrow and Evolution, 3^rd edn, Princeton University Press, Princeton, NJ.

  An excellent discussion of the way te second law of thermodynamics has influenced biological evolution.

Dulbecco, R. (1987) The Design of Life, Yale University Press, New Haven, CT.

  An unusual and excellent introduction to biology.

Frution, J.S. (1972) Molecules and Life: Historical Essays on the Interplay of Chemistry and Biology, Wiley-Interscience, New York.

  This series of essays describes the development of biochemistry from Pasteur’s studies of fermentation to the present studies of metabolism and information transfer. You may want to refer to these essays as you progress through this textbook.

Fruton, J.S. (1992) A Skeptical Biochemist, Harvard University Press, Cambridge, MA.

Jacob, F. (1973) The Logic of Life: A History of Heredity, Pantheon Books, Inc, New York.

  A fascinating historical and philosophical account of the route by which we came to the present molecular understanding of life.

Judson, H.F. (1979) The Eighth Day of Creation: The Makers of the Revolution in Biology, Jonathan Cape, London.

  A highly readable and authoritfative account of the rise of biochemistry and molecular biology in the twentieth century.

Kornberg, A. (1987) The two cultures: chemistry and biology. Biochemistry 26, 6888-6891.

  The importance of applying chemical tools to biological problems, described by and eminent practitioner.

Mayr, E. (1997) This Is Biology: The Science fo the Living World, Belknap Press, Cambridge, MA.

  A history of the development of science, with special emphasis on Darwinian evolution, by and eminent Darwin scholar.

Monod, J. (1971) Chance and Necessity, Alfred A. Knopf, Inc., New York.

An exploration of the philosophical implications of biological knowledge.