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Unformatted text preview: Concepts in Biochemistry
3rd Edition Chapter One
Biochemistry: From Atoms to Molecules to Cells Dr J. Davis Chapter 1 Homework Study Exercises: #4 -7, 11-14. Chapter Seven What is Biochemistry: The study of life at the molecular level. The word "biochemistry" implies the overlap of two major areas of science: 1) Biology and 2) Chemistry. What Processes do all living organisms have in common? 1. Organisms are able to extract nutrient energy from molecules. 2. Organisms grow, differentiate and reproduce.
3. Organisms have ability to respond to changes in their environment.
3 Overall goal of biochemistry: to describe life's processes, applying the principles of chemistry to determine molecular structures, and then to use structures to explain biological function. All organisms are composed of cells, which are themselves composed of thousands of organic and inorganic molecules, plus many large macromolecules. All biological processes involve the interactions of thousands of these small to large molecules (vision, digestion, thinking, movement, and regrettably even illness and disease). Biochemistry is the study of the contributions of both biology and chemistry to understanding biological processes.
4 Biochemistry can be organized into three primary areas! 5 Three major areas of focus in the study of Biochemistry (See Fig 1.1) 1. Structural and Functional biochemistry: discovery of the chemical structures and 3D arrangement of biomolecules. Knowledge of molecular structures is required to the describe / understand the function and purpose of biological processes of the molecules. 2. Informatonal biochemistry: definition of the language for storing biological data and for transmitting the data to all cells and organisms (heredity and expression of genetic information). It also includes those processes that communicate molecular signals to regulate cellular activities (receptors/hormones). Higher organisms are complex, information-processing systems. 3. Bioenergetics--the flow of energy in living organisms, and how energy is transferred from one biochemical process to another. Example; foods contain potential molecular energy that is used to maintain body temperature, regulate the flow of ions in nerve transmission, provide energy for muscle contraction, etc.
6 Roots of Biochemistry
Early History of Biochemistry (Section 1.1) Students read on your own!. See also Figure 1.2. A Distinction between Biochemistry and Molecular biology Molecular biology: coined as a new area of research/scientific funding @ 1938. Focus: application of the tools of the physical sciences to biology, biochemistry, cell biology and genetics. Molecular biologists (currently) study genetic material in cells (DNA/RNA), and its role in information transfer. They use biological experimental techniques involving organisms, recombinant DNA and molecular genetics.
7 Roots of Biochemistry
A Distinction between Biochemistry and Molecular biology (2) Biochemists originally focused (primarily) on the structure and function of All biomolecules. Now, they also focus on use the same techniques as molecular biology. Last ~ 30 years, molecular biology and biochemistry have become indistinguishable, because they attempt to answer the same fundamental question: What is Life?? 8 Fig 1.2 Dates for Nobel prizes (Biology & Chemistry) during last ~200 yrs 9 Fig 1.3 The Biochemists' Periodic Table 10 Composition of Living Matter the Biochemists' Periodic Table
Chemical Elements in Biomolecules Only ~ 30 of the 116+ known elements occur naturally in plants and animals (See Fig 1.3). These elements exist in 3 basic categories: 1) Elements present in large quantities (red) and absolutely essential for life [C, H, O, N, P, & S make up 92 % of the total cell mass]. 2) Trace elements (yellow) present in small quantities and probably essential for life [Ca, Mn, Fe, the nonmetals Cl and I, etc.]. 3) Trace elements (blue) present only is certain select organisms: Al, As, Se, Cd, V, W, F & Br, Mo, etc.
11 Fig 1.4 Elemental Composition of the Universe (blue), the earth's crust (pink( and the human body (purple). It is very likely that elements found in biological organisms were specifically selected according to their abilities to perform certain specific biochemical or structural functions. 12 Combination of Elements into Compounds Students: review the elemental names/symbols (as needed).
The combination of chemical elements into biomolecules provides a wide variety in the possible chemical structures and reactivities observed in nature. Nature's molecules include such examples as: cations(+) / anions(-); both ionic and covalent compounds, metal ions [small biomolecules], all the way up to various types of large (bio)polymers / macromolecules. Examples: Amino acids are building blocks of proteins and enzymes; monosaccharides are building blocks of complex carbohydrates; and lipids (fats) make up three main categories of biochemical molecules that we will study. 13 Combination of Elements into Compounds Many diverse structures exist among organisms but some striking similarities also exist: Example: Organometallic compounds with unique structures (Porphyrin ring), but localized in animals (Heme) or plants (Chlorophyll) only [ See Fig. 1.5] Heme contains Fe(II) ion and is found in oxygen transport proteins (hemoglobin/myoglobin). Chlorophyll, a magnesium porphyrin complex found in green plants/algae, functions as a receptor of light energy.
14 JUST IN TIME REVIEW
Important Functional Groups in Biochemistry Properties and reactions of cellular molecules are best described using the functional group concept (Recall: Organic chemistry). Functional groups are formed by combination of elements into specific structural or biochemical units. These units are important as sites of chemical reactions in biomolecules-- a specific functional group, no matter what type of molecule its in, should undergo the same kinds of chemical reactions. A list of Important functional groups (Students: review these)
15 Important Functional Groups in Biochemistry -1 16 Important Functional Groups in Biochemistry 2 17 1.3 Biological Macromolecules Many molecules found in cells are Very Large (by normal chemistry standards). Three major classes of natural, polymeric macromolecules are found in biological cells: 1) Nucleic acids (nucleotide polymers); 2) Proteins ( amino acid polymers); and 3) Polysaccharides (monosaccharide polymers).
Note: Lipids are a fourth major class of biomolecules, but are not polymers!.
18 1.3 Biological Macromolecules
The major classes of natural (polymeric) macromolecules participate in all the critical biochemical/biological processes in living organisms, including: a) storing and transferring information [nucleic acids], b) catalyzing chemical reactions [the enzymes / proteins]; c) structural proteins & polysaccharides (holding cells together); d) transport proteins (albumin, etc); e) immune defense [protein antibodies]; and f) Many other functions. 19 1.3 Biological Macromolecules
Many of the important molecules studied in biochemistry are very large biomolecules [macromolecules], composed of hundreds / thousands / millions of smaller molecular units = aka monomers [See Figure 1.6]. Cellular Reactions: How are these Macromolecules created? Condensation Reactions a chemical process involving the removal of a molecule of water and the addition of a single monomeric unit to the chain. Cleavage/Hydrolysis Reactions--the reverse of condensation [is used to deconstruct polymers]-- water is used in the cleavage and degradation of a polymer, releasing a monomer each time and adding water See next slide. 20 Cellular reactions used in formation of polymers: Condensation reaction (forward) and Hydrolysis reaction (reverse) --Reactions forming/ degrading an amide linkage in a protein. 21 Examples of types of natural biopolymers 22 Classification of type of polymers 1. Homopolymers polymers containing identical monomeric units. This includes many polysaccharides, such as starch, glycogen, and cellulose (glucose monomers). 2. Heteropolymers occur in proteins, consisting of 20 different amino acids as monomeric building blocks. Different proteins are formed by changing the order / sequence of the AA monomers. DNA is also a heteropolymer, composed of millions of monomeric units called deoxynucleotides [dAMP, dCMP, dTMP, dGMP]. 23 1.4 Organelles, Cells and Organisms In our discussions so far, we have described biomolecules in a stepwise progression starting from the atoms & elements to monomers to functional polymeric biomolecules. The next level of organization that we will encounter has even higher levels or organization and complexity: the Supramolecular assemblies Supramolecular assemblies are organized clusters of macromolecules. Examples: the cell membranes (complexes of proteins/lipids); Chromatin (complexes of DNA/proteins) the Ribosomes (complexes of RNA/proteins); the Cytoskeleton [fibrous protein-containing outer skeleton].
24 1.4 Organelles, Cells and Organisms The unique significance of Supramolecular Assemblies: they are biomolecules with abilities to recognize and interact with each other in specific ways (aka = "Molecular recognition"). Molecular recognition = occurs when molecules that are complementary to each other can interact via formation of many weak and reversible chemical forces/bonds. We will encounter this principle many times in the semester and discuss the forces involved later in the textbook.
25 VIRUSES Viruses are large Primitive/Prototypical examples of Supramolecular Assemblages [See Figures]. Viruses consist a single RNA/DNA molecule wrapped in a protein package. Viruses cannot exist independently and are NOT considered a true independent life-form. They are considered parasites, unable to carry out self-sufficient metabolic processes/reproduction. Viruses, as is well known, are the cause of many plant and animal maladies and disease. 26 Living Cells After supramolecular assemblies, the next higher level of organization is the fundamental unit of life is the Cell. There are two basic classifications of cell types: 1) Prokaryotes, simple, unicellular organisms [bacteria and blue-green algae], lacking a distinct cell nucleus and lacking internal cellular compartmentalization, and 2) Eukaryotes organisms, including plants and animals, composed of cells w. a distinct membrane enclosed nucleus and w. internal compartmentalization of organelles. 3) A third category, called the Archaebacteria or Archea [ancient bacteria] which most closely resemble prokaryotes.
27 A Brief word about Archaebacteria The Archaebacteria (aka extremophiles) closely resemble the prokaryotes, but they differ in their RNA/DNA composition and in their natural environmental preferences. They often grow in high salt (3 M NaCl), high acidity (pH < 3.0 or pH > 9), high temperatures (>120 C (250 F)), low temperatures (< -10 C), high pressures (>100 atm) or low oxygen environments. Biochemists are eager to find out how they maintain and stabilize their macromolecules in these extremes environments [See Window on Biochemistry 1-1 (p 18)]. Note: there are other Extremophiles (not Archaea) which can also thrive in unusual environmental conditions [Bacillus thermophilus] (See next Slides).
28 Some Examples of Extremophiles
1. Thermus aquaticus, a bacteria from hot springs in Yellowstone park, supplies molecular biology with Taq DNA polymerase, an enzyme used in PCR technology. 2. Bacteria found in hot springs in Asia survive at low pH [2-3] (Sulfolobus sp) or high pH [pH > 9 ( Marinospirillium alkaliphilium]. 3. Methanogens, anaerobes that use H2 gas to reduce CO2 to methane, survive 6-7 miles (high pressures) below the surface (Pacific ocean). 4. Some recombinant bacteria can withstand exposure to high levels of radiation (efficient DNA repair enzymes).
29 Characteristics of Living Cells
PROKARYOTIC Cells (1) Prokaryotes are the least developed, but most abundant, (widespread) living cells [See Figure 1.8] 1) Size: ~1-10 M in diameter; Shape: spheroid (cocci); rodlike (bacilli) and helical coils (spirilla). 2) Type of Cell membrane: Membrane surrounds cellular components, which are encapsulated within both a cell membrane and rigid cell wall. Outside surface may often have flagella (for locomotion), and pili (structural features for transfer of DNA during sexual conjugation and for attachment).
30 Figure 1.8 Schematic of a typical prokaryotic cell 31 Prokaryotic Cells
PROKARYOTIC Cells (2) 3) Interior cytoplasm contains a gel-like heterogeneous suspension of biomolecules, including small organics / ions, soluble enzymes, ribosomes, coiled DNA. 4) Most bacteria cells have 1 chromosome = 1 single copy of DNA [the Genome]. See Table 1.1 Molecular Composition and Biological function of Prokaryotic Cell Components. 32 33 Eukaryotic Cells EUKARYOTES includes higher plants, animals, fungi, protozoa, yeast, and some algae [See Fig 1.11]. Cells are much larger than prokaryotes [~10 - 100 m]. Cells are surrounded by a plasma membrane; = a chemical barrier to keep molecules in / out. Plasma membrane also surrounds certain internal organelles inside cell, thus "compartmentalizing" biological function. Organelles = are compartments within membrane-enclosed packages, containing macromolecules that perform specific functions [See Table 1.2] 34 Structure of a Typical Plant Cell 35 Structure of Typical Eukaryotic Animal Cell 36 37 Eukaryotic Cells The Cytoskeleton of a cell gives the cell its shape and is
anchored by protein fibers of various types: 1) microtubules [tubulin], 2) microfilaments [actin] and 3) intermediate filaments [keratin]. 38 A Preview: Storage and transfer of biological information Recall: Biochemistry has three major areas of focus: 1) Structure/function of molecules, 2) Information processing, and 3) Energy transfer. The most important of these may be: biological Information processing, which are essential for the proper growth, reproduction, propagation of biological info to next generations. A VERY brief introduction to INFORMATIONAL BIOCHEMISTRY follows here. 39 A Preview: Storage and transfer of biological information Figure 1.14 shows basic steps in the storage and replication of biological information in DNA (main repository of Genomic information) and its transfer via RNA to synthesize proteins that direct the cellular function and structure. Processes involves: 1) high-fidelity duplication of DNA for transfer into daughter cells during cell division, and 2) expression of stored genomic information, initially in the form of RNA which facilitates the production of proteins (enzymes) that can direct/coordinate the thousands of chemical reactions occurring in the cell.
40 Fig 1.4. A Schematic: Replication of Biochemical information-- to direct the implementation of cell structure and function 41 Storage and Transfer of Biochemical Information
Genome, and resides [in Eukaryotes] in the form of a long, coiled, macromolecule, DNA. Process: DNA, as the major molecular repository of genetic info, stores the information for the synthesis of thousands of proteins, which are available to build all the cellular components for the proper function of the cells. Proteins provide the capability for the cell to produce energy; for synthesis/breakdown of macromolecules, for storage and transport of biomolecules, for muscle contraction/movement, and for cellular communication. The total genetic information located in each cell is the 42 Storage and Transfer of biochemical information Students: Read/skim rest of the chapter on own. Will return and cover this information again in detail when we study DNA/molecular biology in 2- 3 weeks. Also: SEE Biochemistry in the Clinic [p 32] OBESITY. Reminder: See End of Chapter Summaries, Terms important to know/understand. Study Exercises: #4 -7, 11, 1, 19 & 20.
43 Storage and Transfer of biochemcial information The Human Genome Project [HGP] was set up to map and sequence the ~3 billion nucleotide base pairs in the human genome by 2005. A rough draft of the human genome was finished in 2000 [five yrs ahead of schedule]. We now know the locations of thousands of genes that are possibly associated with many diseases including, Cystic Fibrosis, Muscular Dystrophy, several cancers, Parkinson's, Huntington diseases, etc. [See next slide]. 44 45 The Human Genome Project proceeded through a series of maps of finer and finer resolution. 46 Celera followed a different, random "shotgun" approach in which they fragmented DNA and then relied on instrumental and computer-driven techniques to establish the sequence. 47 Storage and Transfer of biochemical information
It is now thought that there are "only" ~25,000 30,000 genes in the human genome, much less than thought before. Genomics, the study of whole sets of genes and their functions, is inspiring research into all aspects of plant and animal life. Several brand new areas of biomedical research have been launched based on this new knowledge of the human genome: 1) Proteomics a new field investigating the hundreds of thousands of protein products made from the genome; 2) Bioinformatics usage of computers to collate and organize the billions of items of genomic data. Other Genomic-related fields of study are listed in the next slide. Many of these fields are some of the hottest areas of biochemical research currently. 48 49 Genomics: Using What We Know
Some Examples of Applicatons of Genomic technology: A bacterial gene (from Bacillus thuringiensis, Bt) has been transplanted into corn. The gene causes the corn to produce a toxin that kills the European corn borer. In 2000, one-quarter of all corn planted in the United States was Bt corn. Soybeans modified to withstand herbicides are widely grown. The soybean crop remains unharmed when the surrounding weeds are killed by the herbicide. 50 More Applications of Genomic technology: Gene therapy is based on the premise that replacement of a disease-causing gene with the healthy gene will cure or prevent a disease. The most clear-cut expectations for gene therapy lie in treating monogenic diseases, those that result from flawed DNA in a single gene. Although little progress has been made since the first gene therapy clinical trials began in 1990, vigorous research into this area continues as new approaches continue to be examined. 51 Genomics: Using What We Know Genomics, the study of whole sets of genes and their functions, is inspiring research into all aspects of plant and animal life. Genomics has greatly accelerated our ability to develop crop plants and farm animals with desirable characteristics and lacking undesirable ones.
Tests are underway with genetically modified coffee beans that are caffeine free, potatoes that absorb less fat when they are fried, and "Golden Rice," a yellow rice that provides the vitamin A desperately needed in poor populations where insufficient vitamin A causes death and blindness. 52 There are genetically engineered salmon that can grow to a marketable size in half the time, and there is the prospect of cloning leaner pigs. Key Questions not yet addressed: Will modified plants and animals intermingle with natural varieties? Should food labels state whether the food contains genetically modified ingredients? Others 53 54 Chapter 1 Homework Study Exercises: #4 -7, 11-14. 55 END OF CHAPTER 1 Chapter Seven ...
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