Biochemistry (mathews 3rd ed) PDF

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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. Comp...

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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. ●

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Outlines sections parallel the organization of the individual chapters in the textbook, with hyperlinks to key concepts, figures, and pathways. Concepts sections contain hyperlinked summaries of the important concepts from each chapter. Terminology sections, which define the important terms from the text on a chapter-by-chapter basis, also include hyperlinks to appropriate figures. 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

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Adenosine Triphosphate (ATP) ATP serves as the general "free energy currency" for virtually all cellular processes. Hydrolysis of ATP is used to drive countless biochemical reactions, including many that are not phosphorylations. It is a direct source of energy for cell motility, muscle contraction, and the specific transport of substances across membranes. The processes of photosynthesis and metabolism of nutrients are used mainly to produce ATP. It is probably no exaggeration to call ATP the single most important substance in biochemistry. The average adult human generates enough metabolic energy to synthesize his or her own weight in ATP every day. ATP is produced in the cell from ADP as a result of three types of phosphorylations - substrate-level phosphorylations, oxidative phosphorylation, and, in plants, photosynthetic phosphorylation. ATP is a source of phosphate energy for synthesis of the other nucleoside triphosphates via the reaction that follows: ATP + NDP ADP + NTP (catalyzed by Nucleoside Diphosphokinase) ATP is also an allosteric effector of many enzymes.

See also: Nucleotides, ATP as Free Energy Currency (from Chapter 12), ADP, AMP, Figure 3.7

Adenosine Diphosphate (ADP) ADP is a nucleotide produced as a result of hydrolysis of ATP in the most common energyyielding reaction of cells. ADP participates in substrate-level phosphorylation, oxidative phosphorylation, and photosynthetic phosphorylation. It is not possible to list here all of the enzymes interacting with ADP. Metabolism of ADP is shown below: 1. ADP ATP + AMP (catalyzed by adenylate kinase). 2. GMP + ATP GDP + ADP (catalyzed by guanylate kinase). 3. NDP + ATP NTP + ADP (catalyzed by nucleoside diphosphokinase). 4. ADP + NADPH dADP + NADP+ (catalyzed by ribonucleotide reductase). ADP is transferred into the mitochondrial matrix by adenine nucleotide translocase and may be a limiting reagent in oxidative phosphorylation.

See also: Phosphorylations, AMP, ATP

Adenosine Monophosphate (AMP) AMP is a common intermediate in metabolism involving ATP. AMP is produced as a result of energyyielding metabolism of ATP in three ways: A. By hydrolysis of a pyrophosphate from ATP (one example is shown in reaction 1 below). B. By transfer of a phosphate from ADP (reaction 2 below). C. By transfer of a pyrophosophate from ATP to another metabolite (reaction 6 below) AMP is also an intermediate in de novo synthesis of ATP (reaction 3 below) and salvage synthesis of ATP (reactions 4, 5, and 8 below). AMP is an allosteric activator of glycogen phosphorylase b, and phosphofructokinase, as well as an allosteric inhibitor of fructose-1,6-bisphosphatase and adenylosuccinate synthetase. AMP is also an allosteric inhibitor of glutamine synthetase, an enzyme with a central role in nitrogen metabolism in the cell. Selected reactions involving AMP 1. Fatty acid + ATP + CoASH Fatty acyl-CoA + AMP + PPi (catalyzed by Fatty acyl-CoA Ligase). 2. 2 ADP ATP + AMP (catalyzed by Adenylate Kinase) 3. Adenylosuccinate Fumarate + AMP (catalyzed by Adenylosuccinate Lyase) 4. PRPP + Adenine AMP + PPi (catalyzed by Phosphoribosyltransferase) 5. ATP + Ribose-5-Phosphate PRPP + AMP (catalyzed by PRPP Synthetase) 6. AMP + H2O NH4+ + IMP (catalyzed by AMP Deaminase)

See also: ATP, ADP, cAMP, AMP-Dependent Protein Kinase

Glycogen Phosphorylase b Glycogen phosphorylase b is the less active form of glycogen phosphorylase. It differs from glycogen phosphorylase a in that it is not phosphorylated and that it requires AMP for activity. Glycogen phosporylase b is a substrate for the enzyme glycogen phosphorylase b kinase, which converts the b form to the a form by adding two phosphates. The reaction is stimulated in the presence of calcium via interaction of calmodulin with glycogen phosphorylase b kinase Two features distinguish glycogen phosphorylase b from the a form: 1. The a form is derived from the b form by phosphorylation of the b form by the enzyme phosphorylase b kinase (Figure 13.18). 2. The b form requires AMP for allosteric activation and is thus active only when cells are at a low energy state.

See also: Mechanism of Activating Glycogen Breakdown, Kinase Cascade, Glycogen Breakdown Regulation, Phosphorolysis, Glycogen, Glucose-1-Phosphate, cAMP

Glycogen Phosphorylase Glycogen phosphorylase catalyzes phosphorolysis of glycogen to glucose-1-phosphate (Figure 13.18). Two forms of the enzyme exist. The relatively "inactive" form 'b' has no phosphate, but can be converted to the more active form 'a' by action of the enzyme glycogen phosphorylase b kinase. Two features distinguish glycogen phosphorylase a from the b form: 1. The a form is derived from the b form by phosphorylation of the b form by the enzyme phosphorylase b kinase. 2. The b form requires AMP for allosteric activation and is thus active only when cells are at a low energy state.

See also: Glycogen Phosphorylase a, Glycogen Phosphorylase b, Glycogen, Kinase Cascade, Glycogen Phosphorylase b Kinase, Figure 16.11

Phosphorolysis Phosphorolysis involves the cleavage of a bond by addition across that bond of the elements of phosphoric acid. An enzyme catalyzing a phosphorolysis is called a phosphorylase, to be distinguished from a phosphatase (or, more precisely, a phosphohydrolase), which catalyzes the hydrolytic cleavage (hydrolysis) of a phosphate ester bond. Energetically speaking, the phosphorolytic mechanism has an advantage in mobilization of glycogen, which yields most of its monosaccharide units in the form of sugar phosphates (glucose-1-phosphate). These units can be converted to glycolytic intermediates directly, without the investment of additional ATP. By contrast, starch digestion yields glucose plus some maltose. ATP and the hexokinase reaction are necessary to initiate glycolytic breakdown of these sugars.

See also: Figure 13.15, Glycogen, Glucose-1-Phosphate, Starch, Glucose, Maltose, Hexokinase

Figure 13.15: Cleavage of a glycosidic bond by hydrolysis or phosphorolysis.

Glycogen Glycogen is a branched polymer of glucose, consisting of main branches of glucose units joined in (1>4) linkages. Every 7-20 residues, (1->6) branches of glucose units are also present. Glycogen is a primary energy storage material in muscle. Individual glucose units are cleaved from glycogen in a phosphorolytic mechanism catalyzed by glycogen phosphorylase. The storage polysaccharides, such as glycogen, are admirably designed to serve their function. Glucose and even maltose are small, rapidly diffusing molecules, which are difficult to store. Were such small molecules present in large quantities in a cell, they would give rise to a very large cell osmotic pressure, which would be deleterious in most cases. Therefore, most cells build the glucose into long polymers, so that large quantities can be stored in a semi-insoluble state. Whenever glucose is needed, it can be obtained by selective degradation of the polymers by specific enzymes.

See also: Phosphorolysis, Glycogen phosphorylase, Figure 13.18, Kinase Cascade, Figure 13.16, Figure 13.17, Polysaccharides, Glycogen Breakdown, Hydrolysis vs Phosphorolysis, Glycogen Breakdown Regulation

-D-Glucose Glucose is a six carbon sugar which can provide a rapid source of ATP energy via glycolysis. Glucose is stored in polymer form by plants (starch) and animals (glycogen). Plants also have cellulose, which is not used to store glucose, but rather provides structural integrity to the cells.

Glucose has an anomeric carbon, which can exist in the and configurations. Glucose can exist in both the D and L forms (though the D-form predominates biologically). It can exist as a straight chain or in ring structures composed of 5 (furanose) or 6 (pyranose) member rings. Metabolic pathways involving glucose Glycolysis Gluconeogenesis Glycogen Synthesis Glycogen Breakdown Cori Cycle Glycoside Formation Other Saccharide Synthesis

See also: Diastereomers (from Chapter 9), Saccharides (from Chapter 9)

Glycolysis Glycolysis is a central metabolic pathway involving metabolism of the sugar glucose. Figure 13.3 shows an overview of the process, being divided into a phase in which ATP energy is invested (see here) and a phase in which ATP energy is generated (see here). The starting point for glycolysis is the molecule glucose and the process ends with formation of two pyruvate molecules. Additional products of glycolysis include two ATPs and two NADHs.

See also: Glycolysis Reaction Summaries, Molecular Intermediates, Glycolysis/Gluconeogenesis Regulation, Gluconeogenesis, Aerobic vs Anaerobic Glycolysis, Pyruvate

INTERNET LINKS: 1. Glycolysis/Gluconeogenesis

Figure 13.3: An overview of glycolysis.

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NADH NADH is a carrier of electrons produced in biological oxidations. The molecule exists in two forms that vary in whether or not they are carrying electrons. NADH is the reduced form of the molecule (carries electrons) and NAD+ is the oxidized form of the molecule (lacks electrons). NADH is produced from NAD+ in reactions such as conversion of acetaldehyde to ethanol by alcohol dehydrogenase (Figure). NADH is converted back to NAD+ by donating electrons (such as in the conversion of pyruvate to lactate) or by depositing electrons into the electron transport system. NADH carries electrons to the electron transport system inside the mitochondrion via a shuttle system (Figure 15.11). Electrons that enter via the shuttle in Figure 15.11a bypass complex I of the electron transport system, whereas electrons that enter via the shuttle in Figure 15.11b enter at complex I. In contrast to the reduced related compound, NADPH, which donates electrons primarily for biosynthetic reactions, NADH primarily donates electrons to the electron transport system for energy generation.

See also: Lactic Acid Fermentation, Alcoholic Fermenation

INTERNET LINK: Nicotinate and Nicotinamide Metabolism

NAD+ NADH is a carrier of electrons produced in biological oxidations. The molecule exists in two forms that vary in whether or not they are carrying electrons. NADH is the reduced form of the molecule (carries electrons) and NAD+ is the oxidized form of the molecule (lacks electrons). NADH is produced from NAD+ in reactions such as conversion of acetaldehyde to ethanol by alcohol dehydrogenase (Figure). NADH is converted back to NAD+ by donating electrons (such as in the conversion of pyruvate to lactate) or by depositing electrons into the electron transport system. NADH carries electrons to the electron transport system inside the mitochondrion via a shuttle system (Figure 15.11). Electrons that enter via the shuttle in Figure 15.11a bypass complex I of the electron transport system, whereas electrons that enter via the shuttle in Figure 15.11b enter at complex I. In contrast to the reduced related compound, NADPH, which donates electrons primarily for biosynthetic reactions, NADH primarily donates electrons to the electron transport system for energy generation.