Table Of Content

Welcome to the Companion Web Site that accompanies the third edition of Biochemistry by Mathews, van Holde, and Ahern. At a time when major technological advances are occurring in both electronics and biochemistry, it is fitting that a web site accompanies this important biochemistry textbook. Companion Web Site Requirements To fully utilize this Companion Web Site it is important to understand the requirements. Get Started! Click on one of the chapters in the "choose a chapter" table to the left. Features of This Companion Web Site Each chapter in the textbook has a corresponding section on the Companion Web Site that contains Outlines, Concepts, Terminology, and Quizzing to help you succeed in your Biochemistry course. G Outlines sections parallel the organization of the individual chapters in the textbook, with hyperlinks to key concepts, figures, and pathways. G Concepts sections contain hyperlinked summaries of the important concepts from each chapter. G Terminology sections, which define the important terms from the text on a chapter-by-chapter basis, also include hyperlinks to appropriate figures. G Quizzing sections help you learn and retain the numerous terms, names, structures, enzymes, and pathways encountered in biochemistry. The Quizzing sections contain over 6000 queries to give you a thorough review and to make it possible to return many times without encountering the same question twice. CD-ROM Access When you're not on-line you can continue your study of biochemistry by using the CD-ROM found in the back of the book. The material available on this web site can also be found on the CD-ROM. Connectivity to Expanded Information on the Internet The internet provides an incredible amount of information in Biochemistry. We have included hyperlinks between the concepts, enzymes, and molecules covered on the Companion Web Site to related information found on hundreds of external web sites. In doing so, the Companion Web Site provides an intellectual bridge between the textbook and an evolving body of knowledge that will undoubtedly grow with time, making this site a tool for learning biochemistry and an ongoing reference. Outline Introduction (Figure 1.1) Revolution in biological sciences Designing Molecules 6-Mercaptopurine 3'-Azido-2',3'-dideoxythymidine (AZT) Isoproterenol What is Biochemistry? Goals of Biochemistry Describe structure, organization, function of cells in molecular terms. Structural Chemistry Metabolism Molecular Genetics Roots of Biochemistry (Figure 1.3) Wohler's synthesis of urea Buchners' fermentation of sugar from yeast extracts Sumner's crystallization of urease Flemming's discovery of chromosomes Mendel's characterization of genes Miescher's isolation of nucleic acids Watson and Crick's structure of DNA Biochemistry as a Discipline Biochemistry as a Chemical Science Amino acids Sugars Lipids Nucleotides Vitamins Hormones Chemical Elements of Living Matter(Figure 1.4, Table 1.1) Biological Molecules Monomers/Polymers (Figure 1.7) Sugar/Polysaccharide Nucleotide/Nucleic Acids Amino acid/Polypeptides (Figure 1.6) Biochemistry as a Biological Science Distinguishing Characteristics of Living Matter Constant renewal of a highly ordered structure accompanied by an increase in complexity of that structure Overcoming entropy requires energy Life is self-replicating Unit of Biological Organization: The Cell (Figure 1.8, Figure 1.9) Prokaryotes (Table 1.2) Eubacteria Archaebacteria Eukaryotes (Compartmentalization of organelles) (Figure 1.11, Figure 1.13) Windows on Cellular Functions: The Viruses New Tools in the Biological Revolution(Figure 1.15) The Uses of Biochemistry Agriculture Medicine Nutrition Clinical Chemistry Pharmacology Toxicology Outline Introduction (Figure 1.1) Revolution in biological sciences Designing Molecules 6-Mercaptopurine 3'-Azido-2',3'-dideoxythymidine (AZT) Isoproterenol What is Biochemistry? Goals of Biochemistry Describe structure, organization, function of cells in molecular terms. Structural Chemistry Metabolism Molecular Genetics Roots of Biochemistry (Figure 1.3) Wohler's synthesis of urea Buchners' fermentation of sugar from yeast extracts Sumner's crystallization of urease Flemming's discovery of chromosomes Mendel's characterization of genes Miescher's isolation of nucleic acids Watson and Crick's structure of DNA Biochemistry as a Discipline Biochemistry as a Chemical Science Amino acids Sugars Lipids Nucleotides Vitamins Hormones Chemical Elements of Living Matter(Figure 1.4, Table 1.1) Biological Molecules Monomers/Polymers (Figure 1.7) Sugar/Polysaccharide Nucleotide/Nucleic Acids Amino acid/Polypeptides (Figure 1.6) Biochemistry as a Biological Science Distinguishing Characteristics of Living Matter Constant renewal of a highly ordered structure accompanied by an increase in complexity of that structure Overcoming entropy requires energy Life is self-replicating Unit of Biological Organization: The Cell (Figure 1.8, Figure 1.9) Prokaryotes (Table 1.2) Eubacteria Archaebacteria Eukaryotes (Compartmentalization of organelles) (Figure 1.11, Figure 1.13) Windows on Cellular Functions: The Viruses New Tools in the Biological Revolution(Figure 1.15) The Uses of Biochemistry Agriculture Medicine Nutrition Clinical Chemistry Pharmacology Toxicology Figure 1.1: Medical applications of biochemistry. 6-Mercaptopurine 6-Mercaptopurine is an analog of hypoxanthine, an intermediate in purine nucleotide biosynthesis. When mercaptopurine is made into a nucleotide by a cell, it stops DNA replication from occurring because it is incorporated into DNA by DNA polymerase instead of the proper nucleotide. 6-Mercaptopurine is an anticancer medication. It inhibits the uncontrolled DNA replication associated with proliferation of white blood cells in leukemia. See also: DNA, Purines, De Novo Biosynthesis of Purine Nucleotides, DNA Replication Overview Hypoxanthine Hypoxanthine is a base found in an intermediate of purine nucleotide biosynthesis. Figure 22.4 summarizes the pathway leading from phosphoribosyl-1-pyrophosphate (PRPP) to the first fully formed purine nucleotide, inosine 5'-monophosphate (IMP), also called inosinic acid. IMP contains as its base, hypoxanthine. Hypoxanthine is also a product of catabolism of purine nucleotides (Figure 22.7). Hypoxanthine can be converted to xanthine by the enzyme xanthine oxidase in the reaction that follows: Hypoxanthine + O2 <=> Xanthine + H2O2 In addition, hypoxanthine can be converted back to IMP in purine nucleotide salvage biosynthesis (by the enzyme HGPRT), as shown in Figure 22.9. Complete deficiency of HGPRT results in gout-related arthritis, dramatic malfunction of the nervous system, behavioral disorders, learning disability, and hostile or aggressive behavior, often self directed. In the most extreme cases, patients nibble at their fingertips or, if restrained, their lips, causing severe self-mutilation. Allopurinol, which is similar to hypoxanthine (see here), is used to treat gout because it inhibits xanthine oxidase, leading to accumulation of hypoxanthine and xanthine, both of which are more soluble and more readily excreted than uric acid, the chemical that causes gout. See also: De Novo Biosynthesis of Purine Nucleotides, Purine Degradation, Excessive Uric Acid in Purine Degradation, Salvage Routes to Deoxyribonucleotide Synthesis, Nucleotide Analogs in Selection INTERNET LINKS: 1. Purine Metabolism 2. Purine and Pyrimidine Metabolism Figure 22.4: De novo biosynthesis of the purine ring, from PRPP to inosinic acid. Phosphoribosyl Pyrophosphate (PRPP) PRPP is an intermediate in nucleotide metabolism. It is found in several de novo and salvage pathways. PRPP is formed by action of the enzyme, PRPP Synthetase, as follows: ATP + Ribose-5-Phosphate <=> PRPP + AMP Enzymes that act on PRPP include Phosphoribosyltransferases (salvage synthesis and de novo synthesis of pyrimidines), PRPP amidotransferase (de novo purine synthesis) See also: De Novo Biosynthesis of Purine Nucleotides, De Novo Pyrimidine Nucleotide Metabolism, Nucleotide Salvage Synthesis Phosphribosyl Pyrophosphate Synthetase (PRPP Synthetase) PRPP synthetase is an enzyme that catalyzes there reaction below (see here also): ATP + Ribose-5-Phosphate <=> PRPP + AMP PRPP is an important intermediate in the de novo synthesis of purines pathway (Figure 22.4). Defects in PRPP synthetase may render it insensitive to feedback inhibition by purine nucleotides. Thus, purine nucleotides are overproduced, leading to excessive uric acid synthesis and gout (Figure 22.9). See also: The Importance of PRPP, De Novo Biosynthesis of Purine Nucleotides, Excessive Uric Acid in Purine Degradation