devlin complete concepts

7/23/2019 Devlin Complete Concepts

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Textbook of Biochemistry

With Clinical Correlations,

Fourth Edition, 1997

Thomas M. Devlin, EditorJohn Wiley

York

Outline with Key Concepts & Comments

Added by Franklin R. Leach

Chapter 1 Eukaryotic Cell Structure

1.1 Overview: Cells and Cellular Compartments

1.1.1 Cells are organized chemical systems.

1.2 Cellular Environment: Water and Solutes1,2,1 Hydrogen bonds form between water molecules

1.2.2 Water has unique solvent properties life is based on water as solvent

1.2.3. Some molecules ionize to form cations and anions4.5.3 Weak electrolytes partially dissociate

1.25Water is a weak electrolyte with pH of 7.01.2.6 Many biological molecules are acids or bases1.2.7 The Henderson-Hasselbalch equation defines the relationship between pH

and concentrations of conjugate acid and base1.2.7.1 pH = pK + log [base}/[acid]

1.2.8 Buffering is important in the control of pH.

1.2.9 The buffer capacity depends on the [acid] and [base].1.3 Organization and Composition of Eukaryotic Cells

1.3.1Cell membranes being semipermeable protect the cell.

1.4 Functional Role of Subcellular Organelles and Membranes1.4.1 The plasma membrane is the cell boundary.1.4.2DNA and RNA synthesis occur in the nucleus.1.4.3.The endoplasmic reticulum is the site of many kinds of synthesis.

1.4.4The Golgi apparatus sequesters and processes proteins.


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1.4.5Mitochondria are the energy factories of the cell.1.4.6Lysosomes function in intracellular digestion.1.4.7Peroxisomes contain oxidative enzymes and metabolize hydrogen

peroxide.1.4.8The cytoskeleton organizes the cells contents.1.4.9 The cytosol contains soluble components, is gel-like, and also has loserorganization.

1.5 The cell is a complex organization where both structure and function areimportant.

Clinical Correlations

cc 1.1 Blood Bicarbonate Concentration in Metabolic Acidosis

cc 1.2 Mitochondrial Diseases

cc 1.3 Lysosomal Enzymes and Gout

cc 1.4 Lysosomal Acid Lipase Deficiency

cc 1.5 Zellweger Syndrome and the Absence of Functional Peroxisomes

Chapter 2 Proteins I: Composition and Structure

2.1 Functional Roles of Proteins in Humans2.1.1 Proteins are important biochemical polymers to both structure and function.

2.2 Amino Acid Composition of Proteins

2.2.1 Proteins are linear polymers of _-amino acids.2.2.2 Common amino acids have a common structure

HRC-COOH

NH22.2.3 The side chain (R) defines the structure as thus the chemical nature of the

particular amino acid.2.2.4 Most amino acids have an asymmetric center and are optically

active.

2.2.5 Amino acids are polymerized into peptides and proteins.2.2.6 Many amino acid derivatives are found in protein. They are

posttranslationaly modified.2.3 Charge and Chemical Properties of Amino Acids and Proteins

2.3.1 The ionization of amino acids and proteins are important in their biologicalfunction.2.3.2 The ionic form of an amino acid is determined by pH.

2.3.3 At the isoelectrical point the molecule has a charge of 0.2.3.4 Titration experiments can characterize ionization behavior of amino acids.

2.3.5 The charge influence movement in an electrical field.


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2.3.6 At the pIthe molecule doesnt move.

2.3.7 Amino acid R-groups can be polar or nonpolar.2.3.8 Amino acids are chemically reactive.

2.4 Primary Structure of Proteins2.4.1 Insulin is an illustration.

2.5 Higher Levels of Protein Organization2.5.1 Proteins have secondary structure.2.5.1.1 Coiled _-helical structure.

2.5.1.2 Flat _-sheets.

2.5.1.3 Additional organization features.

2.5.2 Proteins fold into a 3-D tertiary structure.2.5.3 There can be families of proteins with common structural parameters.

2.5.4 When multiple protein chains interact there is quaternary structure.

2.6 Other Types of Proteins

2.6.1 Examples of fibrous proteins are collagen, elastin, _-keratin, and

tropomysin.

2.6.1.1 Collagen is found in all human tissues and organs.

2.6.1.2 Table 2.10 shows the amino acid composition of collagen.2.6.1.3 Collagen has long stretches where glycine occurs every

third residue.

2.2.1.4 A diagram of collagen is in Figure 2.38.2.6.1.5 There are covalent cross-links in collagen.

2.6.1.6 Elastin has allysine-generated cross-links.

2.6.2 Lipoproteins are comlexes of lipids and proteins.

2.6.3 Glycoproteins contain carbohydrates and protein.2.7 Folding of Proteins from Randomized to Unique Structures: Protein Stability

2.7.1 A possible pathway for protein folding pathway is presented. This is

currently a very active research area.2.7.2 Chaperone proteins assist in the folding process.

2.7.3 Noncovalent forces aid in folding and stability.2.7.4 Denaturation of proteins leads to a loss of structure.

2.8 Dynamic Aspects of Protein Structure2.8.1 Proteins are constantly in motion and are not in the static structure

revealed by x-ray crystallography.

2.9 Methods for Characterization, Purification, and Study of Protein Structure and

Organization2.9.1 Proteins can be separated on the basis of charge.2.9.2 Proteins can be separated on the basis of mass or size.

2.9.3 Proteins can be separated on the basis of chemical properties.

2.9.4 The amino acid sequence of a protein can be determined.2.9.5 The 3-D structures of proteins can be determined by x-ray

crystallograpphic methods.

2.9.6 Proteins can be characterized spectroscopically.


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cc 2.1 Plasma Proteins in Diagnosis of Disease

cc 2.2 Differences in Primary Structure of Insulins Used in Treatment of Diabetes Mellitus

cc 2.3 A Nonconservative Mutation Occurs in Sickle Cell Anemia

cc 2.4 Symptoms of Diseases of Abnormal Collagen Synthesiscc 2.5 Hyperlipidemias

cc 2.6 Hypolipoproteinemias

cc 2.7 Glycosylated Hemoglobin, HbA1c

cc 2.8 Use of Amino Acid Analysis in Diagnosis of Disease

Chapter 3 Proteins II: Structure Function Relationships in

Protein Families

3.1 Overview

3.2 Antibody Molecules: The Immunoglobulin Superfamily3.2.1 Immunogloblin molecules have four peptide chains.3.2.2 The are both constant and variable regions.

3.2.3 Immunoglobulins in a single class contain common homologous regions.

3.2.4 Repeating amino acid sequences and homologous 3-D domains occur within anantibody.

3.2.5 There are two antigen-binding sites per antibody molecule.3.2.6 The immunoglobulin fold is a tertiary structure found in a large family of

proteins with different functions.3.3 Proteins with a Common Catalytic Mechanism: Serine Proteases

3.3.1 Proteolytic enzymes are classified by catalytic mechanisms.

3.3.2 Serine proteases have remarkable specificity.3.3.3 Serine proteases are synthesized as zymogens.

3.3.4 Serpins are natural inhibitors of serine proteases.3.3.5 The serine proteases have similar structure/function relations.

3.3.6 There is amino acid sequence homology.

3.3.7 Tertiary structures are similar.

3.4 DNA-Binding Proteins3.4.1 There are three major structural motifs for DNA-binding proteins.

3.4.2 DNA-binding proteins bind several ways to DNA.

3.5 Hemoglobin and Myoglobin3.5.1 Human hemoglobin occurs in several forms.

3.5.2 A heme prosthetic group is at the oxygen binding site.3.5.3 X-ray crystallography has defined the structures of hemoglobin and myoglobin.

3.5.4 Table 3.9 compares amino acid sequence of hemoglobin and myglobin.3.5.5 A simple equilibrium defines oxygen binding to myoglobin.3.5.6 The re is cooperativity in oxygen binding to hemoglobin.

3.5.7 The affinity of the T conformational state for oxygen is greater than that of theR conformatIon.

3.5.8 The Bohr effect involves dissociation of proton on binding an oxygen.


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cc 3.1 The Complement Proteins

cc 3.2 Functions of Different Antibody Classes

cc 3.3 Immunizationcc 3.4 Fibrin Formation in a Myocardial Infarct and the Action of Recombinant

Tissue Plasminogen Activator (rtPA)

cc 3.5 Involvement of Serine Proteases in Tumor Cell Metastasis

Chapter 4 Enzymes: Classification, Kinetics, and Control

4.1 General Concepts

4.1.1 Enzymes are special proteins that catalyze reactions.4.1.2 Can have no protein cofactors.

4.2 Classification of Enzymes

4.2.1 Class 1 Oxidoreductases4.2.2. Class 2 Transferases4.2.3 Class 3 Hydrolases

4.2.4 Class 4 Lyases

4.2.5 Class 5 Isomerases4.2.6 Class 6 Ligases

4.3 Kinetics4.3.1 Kinetics studies the rate of change of reactants to products.

4.3.2 The rate equation is eq. 4.2.4.3.2.1 Reactions can be characterized bases on order

4.3.2.2 Most reactions are reversible.

4.3.3 Enzymes can be saturated with substrate.4.3.3.1 Specific activity is enzyme units per mg protein.

4.3.3.2 The enzyme binds the substrate.4.3.3.3 The Michaelis-Menten equation is eq 4.12.

4.3.3.4 KM is the substrate concentration that gives half maximum

velocity.

4.3.3.5 The equation can be linearlized4.3.3.5 The equation can be transformed in several ways.

4.3.4 An enzyme catalyzes both forward and reverse directions of a reversible

reaction.4.3.5 Multisubstrate reactions follow either a ping-pong or sequential

mechanism.4.4 Coenzymes: Structure and Function

4.4.1 Coenzymes provide additional organic structures for catalytic function.4.4.2 Adenosine triphosphate can serve as a phosphate donor or a modulator

of activity.

4.4.3 NAD+ and NADP+ are hydrogen-carrying coenzymes derived fromniacin.


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4.4.4 FMN and FAD are hydrogen-carrying coenzymes derived from

riboflavin. 4.4.5 Metal ions can serve various functions as cofactors.4.4.5.1 Metals can have a structural role.

4.4.5.2 Metals can function in redox reactions.4.5 Inhibition of Enzymes

4.5.1 Competitive inhibitors can be reversed by increased [substrate].4.5.2 Noncompetitve inhibitors do not prevent substrate binding.4.5.3 Reversible inhibition leads to covalent modification of an enzyme.

4.5.3.1 Many drugs inhibit enzyme action.

4.5.3.1.1 Sulfa drugs compete with PABA.4.5.3.1.2 Methotrexate competes with folates.4.5.3.1.3 Nonclassical inhibitors that upon an enzymes action

become a highly reactive species.

4.5.3.1.4 Fluorouracil and 6-mercaptopurine are other significantpurine/pyrimidine inhibitors

4.6Allosteric Control of Enzyme Activity4.6.1 Allosteric inhibitors bind at sites different from substrate binding sites.4.6.2 Allosteric enzymes exhibit sigmodial kinetics.4.6.3 Cooperativity explains interaction between ligand sites in an oligomer

protein.

4.6.4 Regulatory subunits modulate the activity of catalytic subunits.4.7 Enzyme Specificity: The Active Site

4.7.1 Complementarity of substrate and enzyme explains substrate secificity.,4.7.2 Not all enzymes can distinguish between two isomers.

4.8 Mechanism of Catalysis4.8.1 Enzymes decrease activation energy.

4.8.1.1 Acid-base mechanisms can be used catalytically.

4.8.1.2 Strain in the substrate can be introduced.4.8.1.3 Covalent bonds are sometimes formed during catalysis.

4.8.1.4 Transition states can be stabilized.4.8.1.5 A decrease in entropy can function in catalysis.

4.8.2 Abzymes are artificially synthesized antibodies with catalytic activity.

4.8.3 Enviornmental factor can influence catalysis.

4.8.3.1 Temperature4.8.3.2 pH

4.9 Clinical Applications of Enzymes4.9.1 Coupled assays often involve changes that be monitored

spectrophotometrically.

4.9.2 Clinical analyzers use immobilized enzymes as reagents.4.9.3 Enyme-linked immunoassays employ enzymes as indicators.

4.9.4 Isozymes are diagnostically important.4.9.5 Some enzymes can be used as therapeutic agents..4.9.6 Enzymes linked to insoluble matrices are used as chemical reactors.

4.10 Regulation of Enzyme Activity



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cc 4.1 A Case of Gout Demonstrates Two Phases in the Mechanism of Enzyme Action

cc 4.2 The Physiological Effect of Changes in Enzyme Km Value

cc 4.3 Mutation of a Coenzyme Binding Site Results in Clinical Disease

cc 4.4 A Case of Gout Demonstrates the Difference Between an Allosteric and the Substrate-

Binding Site

cc 4.5 Thermal Lability of Glucose 6 Phosphate Dehydrogenase Results in Hemolytic Anemia

cc 4.6 Alcohol Dehydrogenase Isoenzymes with Different pH Optima

cc 4.7 Identification and Treatment of an Enzyme Deficiency

cc 4.8 Ambiguity in the Assay of Mutated Enzymes

Chapter 5 Biological Membranes: Structure and Membrane

Transport

5.1 Overview5.1.1 Membranes are important boundaries.

5.2 Chemical Composition of Membranes5.2.1 Lipids are a major component of membranes.

5.2.2 Glycerophospholipids are the most abundant lipids of membranes.5.2.3 Sphingolipids are also present in membranes.

5.2.4 Most membranes contain cholesterol.

5.2.5 The lipid compositions of various membranes differ.5.2.6 Membrane proteins are classified by their easy of removal.

5.2.7 Carbohydrates of membranes are present as glycoprotein or glycolipids.

5.3 Micelles and Liposomes

5.3.1 Lipids form vesicular structures.5.3.2 Liposomes have a membrane structure similar to that of a

biological membrane.

5.4 Structure of Biological Membranes

5.4.1 The fludi mosaic model shown in Fig 5.21 explains membrane structure.5.4.2 Integral membrane proteins are immersed in the lipid bilayer.5.4.3 Perippheral membrane proteins have various modes of attachment.

5.4.4 Human erythrocytes are ideal for studying membrane structure.5.4.5 Lipids are distributed in an asymmetric manner in membranes.5.4.6 Proteins and lipids can diffuse in membranes.

5.5 Movement of Molecules Through Membranes

5.5.1 Some molecules can freely diffuse through membranes.

5.5.2 Movement of molecules across membranes can be facilitated.5.5.2.1 There can be membrane channels.

5.5.2.2 Transporters can function in transport.

5.5.2.3 Transport can be by group translocation.5.5.3 Membrane transport systems have common properties.

5.5.4 There are four common steps in transport.

5.5.4.1 Recognition

5.5.4.2 Translocation5.5.4.3 Release

5.5.4.4 Recovery

5.5.5 Energetics of membrane transport systems.


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6.3.2 Pyruvate dehydrogenase is a multienzyme complex.

6.3.3 Pyruvate dehydrogenase is strictly regulated.6.3.3.1 In bacteria the pryvuate dehydrogenase complex is regulated by

products and substrates.6.3.3.2 In animals there is a covalent modification/demodification.

6.3.4 Acetyl CoA is used by several different pathways.6.4 The Tricarboxylic Acid Cycle6.4.1 The reactions of the tricarboxylic acid cycle are shown in Fig. 6.19.

6.4.2 Conversion of the acetyl group of acetyl CoA to CO2 and H2O conserves

energy.

6.4.3 The activity of the tricarboxylic acid cycle is crefully regulated.6.5 Structure and Compartmentation of the Mitochondrial Membranes

6.5.1 Inner and outer mitochondrial membranes have different compositions

and functions.6.5.2 Mitochondrial inner membranes contain substrate transport systems.

6.5.3 Substrate shuttles transport reducing equivalents across the inner

mitochondrial membrane.6.5.4 Acetyl units are transported by citrate.6.5.5 Transport of adenine nucleotides and phosphate

6.5.5.1 There is an adenine nucleotide translocator.

6.5.5.2 Phosphate is transport by an exchanger.6.5.6 Mitochondria have a specific calcium transport mechanism.

6.6 Electron Transfer6.6.1 Redox reactions

6.6.2 Free-energy changes in redox reactions.6.6.3 Mitochondrial electron transport is a multicomponent system.

6.6.3.1 NAD-linked dehydrogenase

6.6.3.2 Flavin-linked dehydrogenase6.6.3.3 Iron-sulfur centers

6.6.3.4 Cytochromes6.6.3.5 Coenzyme Q

6.6.4 The mitochondrial ele4ctron transport chain is located in the inner

membrane in a specific sequence.

6.6.5 Electron transport can be inhibited at specific sites.6.6.6 Electron transport is reversible.

6.6.7 Oxidative phosphorylation is coupled to electron transport.

6.7 Oxidative Phosphorylation6.7.1 The chemiosmotic-coupling mechanism involves the generation of a

proton gradient and reversal of an ATP-dependent proton pump.


cc 6.1 Pyruvate Dehydrogenase Deficiency

cc 6.2 Fumarase Deficiency

cc 6.3 Mitochondrial Myopathies

cc 6.4 Subacute Necrotizing Encephalopathy

cc 6.5 Cyanide Poisoning


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cc 6.6 Hypoxic Injury

Chapter 7 Carbohydrate Metabolism I: Major Metabolic

Pathways and Their Control

7.1 Overview

7.1.1 Gucose is either the start or end of the major carbohydrate metabolic

pathways.

7.1.2 Glycolysis glucose utilization.7.1.3 Gluconeogeneis glucose synthesis.

7.1.4 your brain needs 100 g of glucose per day it is the major energy

source.7.2 Glycolysis

7.2.1 Glycolysis occurs in all human cells.7.2.1.1 The overall reaction

gl;ucose > 2 pyruvate >2 actyel CoA7.2.1.2 glucose + 6O2 + 38 ADP

3- + 38 Pi2- > 6CO2 + 6 H2O + 38 ATP4-

7.2.1.3 Glucose is metabolized differently in various cells.7.3 The Glycolytic Pathway

7.3.1 See Fig. 7.67.3.2 Glycolysis occurs in three stages (other authors divide into two stages).

7.3.2.1 Stage 1 primes the glucose molecule.

7.3.2.2 Stage 2 splits a phosphorylated intermediate.

7.3.2.3 Stage 3 involves redox reactions and the synthesis of ATP.

7.3.3 A balance of reduction of NAD+ and reoxidation of NADH is required role of lactic dehydrogenase.

7.3.4 NADH generated during glycolysis can be reoxidized via substrateshuttle systems.

7.3.5 Shuttles are important in other redox pathways.

7.3.6 Two shuttle pathways yield different amounts of ATP

7.3.6.1 NADH 3

7.3.6.2 Flavin 27.3.7 Glycolysis can be inhibited at different stages.

7.4 Regulation of the Glycolytic Pathway

7.4.1 The regulatory enzymes are hexokinase, 6-phosphofructo-1-kinase and pyruvate kinase. See Fig 7.13.

7.4.2 Hexokinase and glucokinase have different properties. See Fig. 7.14

7.4.3 6-Phosphofructo-1-kinase is the major regulatory site.7.4.3.1 Crossover theorem explains regulating of 6-phosphofructo-1-

kinase by ATP and AMP.

7.4.3.2 Intracellular pH can regulate 6-phosphofructo-1-kinase.7.4.3.3 Intracellular citrate levels regulate 6-phosphfructo-1-kinase by

cAMP and fructose 2,6-bisphophate.

7.4.3.4 cAMP activates protein kinase A.


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7.4.3.5 6-Phosphofructo-2-kinase and fructose 2,6-bisphosphase are

domains of a bifunctional polypeptide regulated byphosphorylation/dephosphorylation.. See Fig 7.23.

7.4.3.6 The heart contains a different isozyme of the bifunctional enzyme.7.4.4 Pyruvate kinase is a regulated enzyme of glycolysis.

7.5 Gluconeogenesis7.5.1 Glucose is required for survival.7.5.2 The Cori and alanine cycles are paths for lactate and alanine return

to the liver for gluconeogenesis.

7.5.3 Pathway of glucose synthesis from lactate includes lactic dehydrogenase

and pyruvate kinase and requires 6 ATPs.7.5.4 Pyruvate carboxylase and phosphoenolpyruvate carboxykinase also

function in gluconeogeneis.

7.5.5 Gluconeogenesis uses many glycolytic enzymes but in the reversedirection.

7.5.6 Glucose can from synthesized from the carbon chains of glucogenic

amino acids (all except leucine and lysine).7.5.7 Glucose can be synthesized from odd-chain fatty acids via propionylCoA.

7.5.8 Glucose can be synthesized from other sugars.

7.5.8.1 Fructose7.5.8.2 Galactose

7.5.8.3 Mannose7.5.9 Gluconeogenesis requires expenditure of 6 ATPs per glucose formed.

7.5.10 Gluconeogenesis is regulated at the glucose 6-phosphatase,phosphofructokinase, and pyvuate carboxylase steps. These are

catalyzed by enzymes that arent a part of glycolysis.

7.5.11 Glucagon and insulin are hormones that regulate the balance ofgluconeogenesis and glycolysis.

7.5.12 Ethanol ingestion inhibits gluconeogenesis.7.6 Glycogenolysis and Glycogenesis

7.6.1 Glycogen, a storage form of glucose, serves as a ready source of energy.

7.6.2 Glycogen phosphorylase catalyzed the removal of one glucose

unit as glucose 1-phosphate from glycogen.7.6.2 The debranching enzyme is required for complete hydrolysis of

glycogen.

7.6.3 Synthesis of glycogen requires unique enzymes.4.5.3.1Glycogen synthase

7.6.4 There are special features of glycogen degradation and synthesis.7.6.4.1 We store glycogen because it is a good fuel reserve.

4.5.3.2Glycogenin, a protein, is required as a primer for glycogensynthesis.

4.5.3.3 Glycogen limits its own synthesis.4.5.4 Glycogen synthesis and degradation are highly regulated processes.

4.5.4.1Regulation of glycogen phosphorylase. See Fig. 7.57.


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4.5.4.2The cascade that regulates glycogen phosphorylase amplifies asmall signal into a very large effect.

4.5.4.3Regulation of glycogen synthase is shown in Fig. 7.58.4.5.4.4Regulation of phosphoprotein phosphatases which functions for

the removal of phosphates from proteins is part of the scheme.

4.5.5

Effector control of glycogen metabolism4.5.5.1There is negative feedback control by glycogen.4.5.5.2Phosphorylase functions as a glucose receptor in liver.4.5.5.3Glucagon stimulates glycogen degradation in the liver.4.5.5.4Epinephrine stimulates glycogen degradation in the liver.4.5.5.5Epinephrine stimulates glycogen degradtion in heart and skeletal

muscle.

4.5.5.6There is neural control of glycogen degradation in skeletalmuscle.

4.5.5.7Insulin stimulates glycogen synthesis in muscle and liver.Clinical Correlations

cc 7.1 Alcohol and Barbiturates

cc 7.2 Arsenic Poisoning

cc 7.3 Fructose Intolerance

cc 7.4 Diabetes Mellitus

cc 7.5 Lactic Acidosis

cc 7.6 Pickled Pigs and Malignant Hyperthermia

cc 7.7 Angina Pectoris and Myocardial Infarction

cc 7.8 Pyruvate Kinase Deficiency and Hemolytic Anemia

cc 7.9 Hypoglycemia and Premature Infants

cc 7.10 Hypoglycemia and Alcohol Intoxication

cc 7.11 Glycogen Storage Diseases

Chapter 8 Carbohydrate Metabolism II: Special Pathways

8.1 Overview

8.1.1 Pentose phosphate pathway is also known as the hexose

monophopsphate shunt or the 6-phosphogluconate pathway.

8.1.2 The various carbons of sugars can be shuffled via reactions incarbohydrate interconversions.

8.2 Pentose Phosphate Pathway

8.2.1 There are two phases in the pentose phosphate pathway.8.2.2. First, glucose 6-phosphate is oxidized and decarboxylated to a

pentose phosphate.

8.2.3 Then the interconversions of the pentose phosphates lead to

glycolytic intermediates.8.2.4 Glucose 6-phosphate can be completely oxidized to carbon dioxide.

8.2.5 The pentose phosphate pathway produces NADPH.

8.3 Sugar Interconversions and Nucleotide Sugar Formation


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8.3.1 Isomerization and phoshporylation are common reactions for

interconverting carbohydrates.8.3.2 Nucleotide-linked sugars are intermediates in many sugar

transformations.8.3.3 Epimerization interconverts glucose and galactose.

8.3.4 Glucuronic acid is formed by oxidation of UDP-glucose.8.3.5 Decarboxylation, oxidoreduiction, and transamination of sugars producenecessary produts.

8.3.6Sialic acids are derived from N-acetylglucosamine.

8.4 Biosynthesis of Complex Carbohydrates

8.4.1 Glucosyltransferases specifically transfer to other carbohydratecontaining molecules.

8.5 Glycoproteins

8.5.1 Glycoproteins contain variable amount of carbohydrate.8.5.2 Carbohydrates are covalently linked to glycoproteins byN- or O-

glycosyl bonds.

8.5.3 Synthesis ofN

-linked glycoproteins involves dolichol phosphate.8.6 Proteoglycans8.6.1 Hyaluronate is a copolymer ofN-acetylglucosamine and glucuronic acid.

8.6.2 Chondroitin sulfates are the most abundant glycosaminoglycans.

8.6.3 Dermatan sulfate contains L-iduronic acid.8.6.4 Heparin and heparan sulfate differ from other glycosaminoglycans

8.6.5 Kertan sulfate exists in two forms.8.6.6 The biosynthesis of chondroitin sulfate is typical of glycosaminoglycan

formatin.


cc 8.1 Glucose 6 Phosphate Dehydrogenase: Genetic Deficiency or Presence of Genetic VariantsinErythrocytes

cc 8.2 Essential Fructosuria and Fructose Intolerance: Deficiency of Fructokinase and Fructose 1

PhosphateAldolase

cc 8.3 Galactosemia: Inability to Transform Galactose into Glucose

cc 8.4 Pentosuria: Deficiency of Xylitol Dehydrogenase

cc 8.5 Glucuronic Acid: Physiological Significance of Glucuronide Formation

cc 8.6 Blood Group Substances

cc 8.7 Aspartylglycosylaminuria: Absence of 4 L Aspartylglycosamine Amidohydrolase

cc 8.8 Heparin Is an Anticoagulant

cc 8.9 Mucopolysaccharidoses

Chapter 9 Lipid Metabolism I: Utilization and Storage ofEnergy in Lipid Form

9.1 Overview9.1.1 Triacylglycerols are more efficient and qunatitative more important

storage form of energy than glycogen.9.2 Chemical Nature of Fatty Acids and Acylglycerols

9.2.1 Fatty acids are alkyl chains terminating in a carboxyl group.


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9.2.2 Nomenclature of fatty acids. See Table 9.1.

9.2.3 Most fatty acids in humans occur as traiacylglycerols.9.2.4 The hydrophobic nature of lipids is important to their biological

function.9.3 Sources of Fatty Acids

9.3.1 Most fatty acids are supplied in the diet.9.3.2 Palmitate can be synthesized from acetylCoA.9.3.3 Formation of malonyl CoA is the commitment step of fatty acid

synthesis.

9.3.4 The reaction sequence of fatty acid synthesis is shown in Fig. 9.7.

9.3.5 Mammalian fatty acid synthase is a multifunctional polypeptide.9.3.6 Stoichiometry 8 acetyl CoAs, 7 ATPs, 14 NADPHs, and 14

protons are used to make palmitate.

9.3.7 Acetyl CoA must be transported from mitochondria to the cytosol forpalmitate synthesis.

9.3.8 Palmitate is the precursor of other fatty acids.

9.3.8.1 Elongation reactions add carbons.9.3.8.2 Desaturation reactions removed hydrogens.9.3.8.3 A series of reactions is involved in the synthesis and

modification of polyunsaturated fatty acids.

9.3.8.4 Hydroxy fatty acids are formed in nerve tissue.9.3.9 Fatty acid synthesis can produce fatty acids other than palmitate.

9.3.10 Fatty acyl CoAs may be reduced to fatty alcohols.9.4 Storage of Fatty Acids as Triacylglycerols

9.4.1 Triacylglycerols are synthesized from fatty acyl ColAs andglycerol 3-phsphate in most tissues.

9.4.2 Mobilization of triacylglycerols requires hydrolysis.

9.5 Methods of Interorgan Transport of Fatty Acids and Their Primary Products9.5.1 Lipid-based energy is transported in the blood in different forms.

9.5.1.1 Plasma lipoproteins can tracylglycerols and other lipids.9.5.1.2 Fatty acids can be bound to serum albumin.

9.5.1.3 Ketone bodies are a lipid-based energy source used in starvation.

9.5.2 Lipases must hydrolyze blood triacylglycerols for their fatty

acids to become available to tissues.9.6 Utilization of Fatty Acids for Energy Production

9.6.1 -Oxidation of straight-chain fatty acids is the major energy-producingprocess.

9.6.1.1 Fatty acids are activated by conversion to fatty acyl CoA.

9.6.1.2 Carnitine carries acyl groups across the mitochondrial membrane.9.6.1.3 -Oxidation is a sequence of four reactions.9.6.2 Comparison of the b-oxidation scheme with palmitate biosynthesis. See

table 9.4.

9.6.3 Some fatty acids require modification of-oxidation for metabolism.9.6.3.1 Proprionyl CoA is produced by oxidation of odd-chain fatty acids.

9.6.3.2 Oxidation of unsaturated fatty acids requires additional enzymes.9.6.3.3 Some fatty acids undergo -oxidation.


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9.6.3.4 -Oxidation gives rise to a dicarboxylic acid.9.6.4 Ketone bodies are formed from acetyl CoA.

9.6.4.1 HMG CoA is an intermediate in the synthesis of acetoacetate from

acetyl CoA.9.6.4.2 Acetoacetate forms both D--hydroxybutyrate and acetone.

9.6.4.3 Utilization of ketone bodies by nonhepatic tissues requiresformation of acetoacetyl CoA.

9.6.4.4 Starvation and certain pathological conditions lead to ketosis.

9.6.5 Peroxisomal oxidation of fatty acids serves many functions.


cc 9.1 Obesity

cc 9.2 Leptin and Obesity

cc 9.3 Genetic Abnormalities in Lipid Energy Transport

cc 9.4 Genetic Deficiencies in Carnitine or Carnitine Palmitoyl Transferase

cc 9.5 Genetic Deficiencies in the Acyl CoA Dehydrogenasescc 9.6 Refsum's Disease

cc 9.7 Diabetic Ketoacidosis

Chapter 10 Lipid Metabolism II: Pathways of Metabolism of

Special Lipids

10.1 Overview

10.2 Phospholipids

10.2.1 Phospholipids contain 1,2-diacylglycerol and a base connected by a

phosphodiester bridge.10.2.2 Phospholipids in membranes have various functions.

10.2.2.1 Dipalmitoyllecithin is necessary for normal lung function.10.2.2.2 Inositides play a role in signal transduction.

10.2.2.3 Phosphatidylinositol serves to anchor glycoproteins to the plasma

membrane.

10.2.3 Biosynthesis of phospholipids.10.2.3.1 Phosphatidic acid is synthesized from -glycerophosphate and

fatty acyl CoA.10.2.3.2 Specific phospholipids are synthesized by addition of a base to

diacylglycerol.

10.2.3.3 The asymmetric distribution of fatty acids in phospholipids is dueto remodeling reactions.

10.2.3.4 Plasmalogens are synthesized from fatty alcohol.

10.3 Cholesterol

10.3.1 Cholesterol, an alicyclic compound, is widely distributed in freeand esterified forms.

10.3.2 Cholesterol is a membrane component and precursor of bile salts and

steroid hormones.


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10.3.3 Cholesterol is synthesized from acetyl CoA.

10.3.3.1 Mevalonic acid is a key intermediate.10.3.3.2 Mevalonic acid is a precursor of farnesyl pyrophosphate.

10.3.3.3 Cholesterol is formed from farnesyl pyrophosphate via squalene.10.3.4 Cholesterol biosynthesis is carefully regulated.

10.3.5 Plasma cholesterol is in a dynamic state.10.3.6 Cholesterol is excreted primarily as bile acids.10.3.7 Vitamin D is synthesized from an intermediate of cholesterol

biosynthesis dehydrocholesterol.

10.4 Sphingolipids

10.4.1 Biosynthesis of sphingosine10.4.2 Ceramides are fatty acid amide derivatives of sphingosine.

10.4.3 Sphingomyelin is the only sphingolipid containing phosphorus.

10.4.3.1 Sphingomyelin is synthesized from a ceramide andphosphatidylcholine.

10.4.4 Glycosphingolipids usually have a galactose or glucose unit.

10.4.4.1 Cerebrosides are glycosylceramides.10.4.4.2 Sulfatide is a sulfuric acid ester of galactocerebroside.10.4.4.3 Globosides are ceramide oligosacchrides.

10.4.4.4 Gangliosides contain sialic acid.

10.4.5 Sphingolipidoses are lysomal storage disease with defect in thecatabolic pathway for sphingolipids.

10.4.5.1 Diagnostic enzyme assays for sphingolipidoses.10.5 Prostaglandins and Thromboxanes

10.5.1 Prostaglandins and thromboxanes are derivatives of twenty-carbon,monocarboxylic acids.

10.5.2 Synthesis of prostaglandins involvess a cyclooxygenase.

` 10.5.2.1 Prostaglandin production is inhibited by steroidal andnonsteroidal anti-inflammatory agents.

10.5.3 Prostaglandins exhibit many physiological effects.10.6 Lipoxygenase and Oxyeicosatetraenoic Acids

10.6.1 Monohydroperoxyeicostetraenoic acids are produts of

lipoxygenase action.

10.6.2 Leukotrienes and hydroxyeicostertraenoic acids are hormonesderived from HPETEs.

10.6.3 Leukotrienes and HETEs affect several physiological processes.


cc 10.1 Respiratory Distress Syndromecc 10.2 Treatment of Hypercholesterolemia

cc 10.3 Atherosclerosis

cc 10.4 Diagnosis of Gaucher's Disease in an Adult

Chapter 11 Amino Acid Metabolism

11.1 Overview


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11.1 Human have forgotten how to synthesize 10 different amino acids.

These must be supplied in the diet. They are listed in Table11.2 Incorporation of Nitrogen into Amino Acids

11.2.1 Most amino acids are obtained from the diet. It is cheaper to importthan manufacture.

11.2.2 Amino groups are transferred between different amino acids using ketoacid intermediates and vitamin B6 coenzymes.11.2.3 Pyridoxal phosphate is the cofactor for aminotransferases.

11.2.4 Glutamte dehydrogenase incorporates and produces ammonia.

11.2.5 Free ammonia is incorporated into and produced from glutamine.

11.2.6 The amide group of asparagine is derived from glutamine.11.2.7 Amino acid oxidases remove amino groups.

11.3 Transport of Nitrogen to Liver and Kidney

11.3.1 Protein is degraded on a regular basis.11.3.2 Amino acids are transported from muscle after proteolysis.

11.3.3 Ammonia is released in the liver and kidney.

11.4 Urea Cycle11.4.1 The nitrogens of urea come from ammonia and aspartate.11.4.2 The synthesis of urea requires five enzymes

11.4.2.1 Carbamoyl phosphate synthetase I

11.4.2.2 Ornithine transcarbamoylase11.4.2.3 Argininosuccinate synthetase

11.4.3.4 Argininosuccinate lyase.11.4.3.5 Arginase.

11.4.3 Urea synthesis is regulated by an allosteric effector (N-acetylglutamate)and enzyme induction.

11.4.4 Metabolic disorders of urea synthesis have serious results.

11.5 Synthesis and Degradation of Individual Amino Acids11.5.1 Glutamate is a precursor of glutahione and -aminobutyrate.11.5.2 Arginine is also synthesized in intestines.

11.5.3 Ornithine and proline are both synthesized from glutamate.11.5.4 Serine and glycine are synthesized from 3-phosphoglycerate.

11.5.5 Tetrahydrofolate is a cofactor in many reactions of amino acids as a

one-carbon carrier.11.5.6 Threonine is usually metabolism to lactate.

11.5.7 Phenylalanine and tyrosine11.5.7.1 Tyrosine is the first intermediate in phenylalanine metabolism.

11.5.7.2 Dopamine, epinephrine, and norepinephrine are derivatives of

tyrosine.11.5.7.3 Tyrosine is involved in synthesis of melanin, thyroid hormone,and quinoproteins.

11.5.8 Methionine and cysteine

11.4.8.1 Methionoine is an essential amino acid.11.4.8.2 Cysteine is made from serine.

11.4.8.2.1 Methionine first reacts with ATP.

11.4.8.2.2 S-Adenosylmethioine is a methyl groups donor.


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11.4.8.2.3 AdoMet is the precursor of spermidine and spermine.

11.4.8.2.4 Metabolism of cysteine produces sulfur-containgcompounds.

11.5.9 Tryptophan (See Fig. 11.66)11.5.9.1 Tryptophan is a precursor of NAD.

11.5.9.2 Pyridoxal phosphate has a prominent role in tryptophanmetabolism.11.5.9.3 Kynurenine gives rise to neurotransmitters.

11.5.9.4 Serotonin and melatonin are tryptophan derivatives.

11.5.9.5 Tryptophan induces sleep.

11.5.9.6 Initial reaction of BCAA (branched chain) metabolism are shared.11.5.9.7 Pathways of valine and isoleucine metabolism are similar.

11.5.9.8 The leucine pathway differs from those of the other two

branched-chain amino acids.11.5.9.9 Propionyl CoA is metabolized to succinyl CoA.

11.5.10 Lysine

11.5.10.1 Carnitine is derived from lysine11.5.11 Histidine11.5.11.1 Urinary formiminoglutamate is diagnostic for folate

deficieny.

11.5.11.2 Histiamine, carnosine, and anserine are produced fromhistidine.

11.5.11.3 Creatine11.5.12 Glutahtionine

11.5.12.1 Glutathione is synthesized from three amino acids.11.5.12.2 The -glutamyl cycle transports amino acids.11.5.12.3 Glutathione concentration affects the response to toxins.


cc 11.1 Carbamoylphosphate Synthetase and N-Acetylglutamate Synthetase Deficiencies

cc 11.2 Deficiencies of Urea Cycle Enzymes

cc 11.3 Nonketotic Hyperglycinemia

cc 11.4 Folic Acid Deficiency

cc 11.5 Phenylketonuria

cc 11.6 Disorders of Tyrosine Metabolism

cc 11.7 Parkinson's Disease

cc 11.8 Hyperhomocysteinemia and Atherogenesis

cc 11.9 Other Diseases of Sulfur Amino Acids

cc 11.10 Diseases of Metabolism of Branched Chain Amino Acids

cc 11.11 Diseases of Propionate and Methylmalonate Metabolism

cc 11.12 Diseases Involving Lysine and Ornithine

cc 11.13 Histidinemia

cc 11.14 Diseases of Folate Metabolism

Chapter 12 Purine and Pyrimidine Nucleotide Metabolism

12.1 Overview


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12.1.1 The author of this chapter limited his discussion to only humans.

12.2 Metabolic Functions of Nucleotides12.2.1 Roles of nucleotidetides

12.2.1.1 Energy metabolism12.2.1.2 Monomeric units of nucleic acids

12.2.1.3 Regulators12.2.1.4 Precursors12.2.1.5 Components of coenzymes (This is a subclass of 4)

12.2.1.6 Activated intermediates (Similar to1)

12.2.1.7 Allosteric effectors (I consider this a subclass of 3)

12.2.2 The distribution of nucleotides vary with cell type.12.3 Chemistry of Nucleotides

12,3,1 Properties of nucleotides

12.3.1.1 Absorb UV light12.3.1.2 RNA digested by base.

12.4 Metabolism of Purine Nucleotides

12.4.1 The purine nucleotides are synthesized by a series of reactionsto form IMP. See fig 12.7.12.4.2 IMP is the common precursor for AMP and GMP. See Fig. 12.10/

12.4.3 Purine nucleotide synthesis is highly regulated.

12.4.4 Purine bases and nucleotides can be salvaged to reform nucleotides.12.4.5 Purine nucleotides can be interconverted to maintain the appropriate

balance of adenine and guanine nucleotides.12.4.6 GTP is a precursor of tetrahydrobiopterin.

12.4.7 The end product of purine degradation in humans is uric acid.12.4.8 Uric acid is formed by xanthine oxidase action.

12.5 Metabolism of Pyrimidine Nucleotides

12.5.1 Pyrimidine nucleotides are synthesized by a series of reactionleading to UMP. See Fig 12.17.

12.5.2 Pyrimidine nucleotide synthesis in humans is regulated at the levelof carbamoyl phosphate synthetase II.

12.5.3 Pyrimidine bases are salvaged to reform nucleotides.

12.6 Deoxyribonucleotide Formation

12.6.1 Deoxyribonucleotides are formed by reduction of ribonucleotidediphopsphates.

12.6.2 Deoxythymidylate synthesis requires N5,N10-methylene

tetrahydrofolate.12.6.3 Pyrimidine interconversions emphasize deoxyribopyrimidine

nucleotiside and nucleotides.12.6.4 Pyrimidne nucleotides are degraded to -amino acids.12.7 Nucleoside and Nucleotide Kinases

12.7.1 ATP can donate a phosphate to form the other NTPs.

12.8 Nucleotide Metabolizing Enzymes as a Function of the Cell Cycle and Rateof Cell Division

12.8.1 Enzymes of purine and pyrimidine nucleotide synthesis are elevated

during the S phase of the cell cycle.


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12.9 Nucleotide Coenzyme Synthesis

12.9.1 FAD see Fig. 12.33.12.9.2 CoA see Fig. 12.34.

12.10 Synthesis and Utilization of 5-Phosphoribosyl-1-pyrophosphate12.10.1 De novo synthesis of purines.

12.10.1.1 Synthesis of 5-phosphoribosylamine.12.10.2 Salvage of purine bases12.10.3 De novo synthesis of pyrimidines.

12.10.4 Salvage of pyrimdines.

12.10.5 Synthesis of NAD+.

12.11 Compounds that Interfere with Cellular Purine and Pyrimidine NucleotideMetabolism: Chemotherapeutic Agents

12.11.1 Antimetabolites are often structural analogs of bases or nucleosides.

12.11.2 Antifolates inhibit formation of tetrahydrofolate.12.11.3 Glutamine anatgonists inhibit enzymes that utilize glutamine as

nitrogen donors.

12.11.4 Other agents inhibit cell growth by interfering with nucleotidemetabolism.12.11.5 Purine and pyrimidine analogs can be antivirals.

12.11.6 Resistance against these agents can develop.


cc 12.1 Gout

cc 12.2 Lesch-Nyhan Syndrome

cc 12.3 Immunodeficiency Diseases Associated with Defects in Purine Nucleoside Degradation

cc 12.4 Hereditary Orotic Aciduria

Chapter 13 Metabolic Interrelationships

13.1 Overview

13.1.1.Interrelationship examined in this chapter.

13.1.2 Feed-starve cycle13.1.3 ATP cycle

13.2 Starve-Feed Cycle

13.2.1 In the well-fed state the diet supplies the energy requirement. See Fig.13.2.

13.2.2 In the early fasting state hepatic glycoenolysis is an important source of

blood glucose.13.2.3 The fasting state requires gluconeogenesis from amino acids and

glycerol.

13.2.4 In the early refed state, fat is metabolized normally, but normal glucosemetabolism is slowly reestablished. See Fig. 13.6.

13.2.5 Other interorgan metabolic interactions

13.2.5.1 Gut and kidney function together in the synthesis of arginine fromglutamine.


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13.2.5.2 Liver provides glutathione for other tissues.

13.2.5.3 Kidney and liver provide carnitine for other tissues.13.2.6 Energy requirements, reserves, and caloric homeostasis

13.2.7 Glucose homeostasis has five stages. See Fig. 13.10.13.3 Mechanisms Involved in Switching the Metabolism of Liver Between the

Well-Fed State and the Starved State13.3.1 Substrate availability controls many metabolic pathways.13.3.2 Negative and positive allosteric effectors regulate key enzymes.

13.2.3 Covalent modificaiton and demodification regulates key enzymes.

13.2.4 Changes in levels of key enzymes are a longer term adaptive

mechanism.13.4 Metabolic Interrelationships of Tissues in Various Nutritional and

Hormonal States

13.4.1 Staying in the well-fed state results in obesity and insulin resistance.13.4.2 Noninsulin-dependent diabetes mellitus

13.4.3 Insulin-dependent diabetes mellitus

13.4.4 Aerobic and anaerobic exercise use different fuels.13.4.5 Changes in pregnancy are related to fetal requirements and hormonalchanges.

13.4.6 Lactation requires synthesis of lactose, triacyglycerol, and protein

13.4.7 Stress and injury lead to metabolic changes.13.4.8 Liver disease causes major metabolic derangements.

13.4.9 In renal disease nitrogenous wastes accumulate.13.4.10 Oxidation of ethanol in liver alters the NAD+/NADH ratio.

13.4.11 In acid-base regulation, glutamine plays a pivotal role.13.4.12 The colon salvages energy from the diet.


cc 13.1 Obesity

cc 13.2 Protein Malnutrition

cc 13.3 Starvation

cc 13.4 Reye's Syndrome

cc 13.5 Hyperglycemic, Hyperosmolar Coma

cc 13.6 Hyperglycemia and Protein Glycosylation

cc 13.7 Noninsulin-Dependent Diabetes Mellitus

cc 13.8 Insulin-Dependent Diabetes Mellitus

cc 13.9 Complications of Diabetes and the Polyol Pathway

cc 13.10 Cancer Cachexia

Chapter 14 DNA I: Structure and Conformation

14.1 Overview

14.1.1 DNA can transform cells.14.1.2 DNAs information capacity is enormous.

14.2 Structure of DNA

14.2.1 Nucleotides joined by phosphodiester bonds form polynucleoties.14.2.2 Nucleases hydrolyze phosphodiester bonds.


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14.2.3 Periodicity leads to secondary structure/

14.2.3.1 Forces that determine polynucleotide confomation.14.2.3.1.1 Stacked

14.2.3.1.2 Hydrophobic14.2.3.1.3 Dipole-induced dipole interactions

14.2.3.2 DNA double helix14.2.4 Many factors stabilize DNA structure.14.2.4.1 Denaturation

14.2.4.2 Renaturation

14.2.4.3 Hybridization

14.2.4.4 DNA probes14.2.4.5 Heteroduplexes

14.3 Types of DNA Structure

14.3.1 Size of DNA is highly variable.14.3.1.1 Techniques for determining DNA size

14.3.2 DNA may b3 linear or circular

14.3.2.1 Double-stranded circles14.3.2.2 Single-stranded DNA14.3.3 Circular DNA is a superhelix.

14.3.3.1 Geometric description of superhelical DNA.

14.3.3.2 Topoisomerases14.3.4 Alternative DNA conformations

14.3.4.1 DNA bending14.3.4.2 Cruciform DNA

14.3.4.3 Triple-standed DNA14.3.4.4 Four-stranded DNA.

14.3.4.5 Slipped DNA.

14.3.5 Nucleoproteins of eukaryotes contain histones and nonhistone proteins.14.3.5.1 Nucleosomes and polynucelosomes.

14.3.5.2 Polynucleosome packing into higher structures.14.3.6 Nucleoproteins of prokaryotes are similar to those of eukaryotes.

14.4 DNA Structure and Function

14.4.1 Restriction endonuclease and palindromes

14.4.2 Most prokaryotic DNA codes for specific proteins.14.4.3 Only a small percentage of eukaryotic DNA codes for structural genes.

14.4.4 Repeated sequences

14.4.4.1 Single-copy DNA14.4.4.2 Moderately reiterated DNA

14.4.4.3 Highlky reiterated DNA14.4.4.4 Inverted repeat DNA

14.4.5 Mitochondrial DNA.


cc 14.1 DNA Vaccines

cc 14.2 Diagnostic Use of Probes in Medicine

cc 14.3 Topoisomerases in Treatment of Cancer


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cc 14.4 Hereditary Persistence of Fetal Hemoglobin

cc 14.5 Therapeutic Potential of Triplex DNA Formation

cc 14.6 Expansion of DNA Triple Repeats and Human Disease

cc 14.7 Mutations of Mitochondrial DNA: Aging and Degenerative Diseases

Chapter 15 DNA II: Repair, Synthesis, and Recombination

15.1 Overview

15.2 Formation of the Phosphodiester Bond in Vivo15.2.1 DNA-dependent DNA polymerase ofE. coli.

15.2.1.1 Synthetic activity.15.2.1.2 Proofreading activity

15.2.1.3 Structure of polymerases15.2.2 Eukaryotic DNA polymerases

15.3 Mutation and Repair of DNA

15.3.1 Mutations are stable change in DNA structure.

15.3.1.1 Chemical modificaion of bases.

15.3.1.2 Radiation damage15.3.1.3 DNA polymerase errors

15.3.1.4 Stretching of the double helix.

15.3.2 DNA is repaired rather than degraded.. 15.3.2.1 Excision repair inE. coli.

1.4.6.1.1 Excision repair in eukaryotes.1.4.6.1.2 Mismatch repair1.4.6.1.3 Mechanism that reverse damage1.4.6.1.4 Postreplication repair.1.4.6.1.5 SOS postreplication repair.

1.5DNA Replication15.4.1 Complementary strands are basic to the mechanism of replication.

15.4.1.1 Replication is semiconservative.15.4.1.2 A primer is required.

15.4.1.3 Both strands of DNA serve as templates concurrently.15.4.1.4 Synthesis is discontinuous.

15.4.1.5 Macroscopic synthesis is as a rule bidirectional15.4.1.6 Strands must unwind and separate.

1.5.6 Eschericia coli provides the basic model for replication of DNA>15.4.2.1 Initiation and progression of DNA synthesis.

1.5.6.1Termination of DNA synthesis.1.5.6.2Rolling circle model for replication.

1.5.7 Eukaryotic DNA replication.15.4.3.1 Role eukaryotic DNA polymerases

1.5.7.1Initiation of eukaryotic DNA replication.1.5.8 DNA replication at the end of linear chromosomes.

15.4.4.1 Prokaryotic replication1.5.8.1Eukaryotic replication: telomerases.

1.5.9 DNA can be synthesized using an RNA template.


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1.5.10 DNA replication, repair, and transcription are closely coordinated.1.6DNA Recombination

15.5.1 Homologous recombination.

15.5.1.1. Enzymes and proteins that catalyze homologous recombination1.6.6 Site-specific recombination.1.6.7

Transposition.1.7Sequencing of Nucleotides in DNA

15.6.1 Restriction maps give the sequence of segm,ents of DNA.


cc 15.1 Mutations and the Etiology of Cancer

cc 15.2 Defects in Nucleotide Excision Repair and Hereditary Diseases

cc 15.3 DNA Ligase Activity and Bloom Syndrome

cc 15.4 DNA Repair and Chemotherapy

cc 15.5 Mismatch DNA Repair and Cancer

cc 15.6 Telomerase Activity in Cancer and Aging

cc 15.7 Inhibitors of Reverse Transcriptase in Treatment of AIDS

cc 15.8 Immunoglobulin Genes Are Assembled by Recombinationcc 15.9 Transposons and Development of Antibiotic Resistance

cc 15.10 DNA Amplification and Development of Drug Resistance

cc 15.11Nucleotide Sequence of the Human Genome

Chapter 16 RNA: Structure, Transcription, and Processing

16.1 Overview16.1. The central dogma. DNA >RNA>protein

16.2 Structure of RNA

16.2.1 RNA is a polymer of ribonucleoside 5-monophosphates.

16.2.2. Secondary structure of RNA involves intramolecular base pairing.16.2.3 RNA molecules have tertiary structure.

16.3 Types of RNA

16.3.1 Transfer RNA has two roles: accepting activated amino acids andrecognizing codons in mRNA.

16.3.2 Ribosomal RNA is part of the protein synthesis apparatus.

16.3.3 Messenger RNAs carry the information for the primary structure of

proteins.

16.3.4 Mitochondria contain unique RNA species.16.3.5 RNA in ribonucleoprotein particles

16.3.6 Some RNAs have catalytic activity.

16.3.7 RNAs can form binding sites for other molecules.16.4 Mechanisms of Transcription

16.4.1 The initial process of RNA synthesis is transcription.

16.4.2 The template for RNA synthesis is DNA.

16.4.3 RNA polymerase catalyzes the transcription process.16.4.4 The steps of transcription in prokaryotes have been determined.

16.4.4.1 Initiation

16.4.4.2 Elongation


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16.4.4.3 Termination

16.4.5 Transcription in eukaryotes involves many additional molecular events.16.4.5.1 The nature of active chromatin.

16.4.5.2 Enhancers16.4.5.3 Transcription of ribosomal RNA genes.

16.4.5.4 Transcription by RNA polymerase II.16.4.5.5 Promoters for mRNA synthesis16.4.5.6 Transcription by RNA polymerase III

16.5 Posttranscriptional Processing

16.5.1 Transfer RNA precursors are modified by cleavage, additions, and

base modification.16.5.1.1 Cleavage

16.5.1.2 Additions

16.5.1.3 Modified nucleosides16.5.2 Ribosomal RNA processing releases the various RNAs from a longer

polymer.

16.5.3 Messenger RNA processing requires maintenance of the codingsequence.16.5.3.1 Blocking of the 5 terminus and poly(A) synthesis

16.5.3.2 Removal of introns from mRNA precursors.

16.5.3.3 Mutations in splicing signals cause human disease.16.5.3.4 Alternate pre-mRNA splicing can lead to multiple proteins being

made from a single DNA coding sequence.16.6 Nucleases and RNA Turnover


cc 16.1 Staphylococcal Resistance to Erythromycin

cc 16.2 Antibiotics and Toxins that Target RNA Polymerasecc 16.3 Fragile X Syndrome: A Chromatin Disease?

cc 16.4 Involvement of Transcriptional Factors in Carcinogenesis

cc 16.5 Thalassemia Due to Defects in Messenger RNA Synthesis

cc 16.6 Autoimmunity in Connective Tissue Disease

Chapter 17 Protein Synthesis: Translation and

Posttranslational Modifications

17.1 Overview

17.2 Components of the Translational Apparatus17.2.1 Messenger RNA is the carrier of genetic information from DNA.17.2.2 Ribosomes are workbenches for protein biosynthesis.

17.2.3 Transfer RNA and activating enzymes act as a bilingualtranslator molecule.

17.2.4 The genetic code uses a four-letter alphabet of nucleotides.

17.2.5 Condons in mRNA are three-letter words.17.2.5.1 Punctuation: AUG is start and UAG, UAA, and UGA are stops.


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17.2.6 Codon-anticodon interactions permit reading of mRNA.

17.2.6.1 Breaking the genetic code.17.2.6.2 Mutations

17.2.7 Aminoacylation of tRNA activates amino acids for protein synthesis.17.2.7.1 Specificity and fidelity of aminoacylation reactions.

17.3 Protein Biosynthesis17.3.1 Translation is directional and colinear with mRNA.17.3.2 Initiation of protein synthesis is a comp9lex process.

17.3.3 Elongation is the stepwise formation of peptide bonds.

17.3.4 Termination of polypeptide synthesis requires a stop codon.

17.3.5 Translation has significant energy cost.17.3.6 Protein synthesis in mitochondria differs slightly.

17.3.7 Some antibiotics and toxins inhibit protein biosynthesis.

17.4 Protein Maturation: Modification, Secretion, and Targeting17.4.1 Proteins for export follow the secretory pathway.

17.4.2 Glycosylation of proteins occurs in the endoplasmic reticulum

and Golgi apparatus.

17.5 Organelle Targeting and Biogenesis

17.5.1 Sorting of proteins targeted for lysosomes occurs in the secretory

pathway.17.5.2 Import of protein by mitochondria requires specific signals.

17.5.3 Targeting to other organelles requires specific signals.17.6 Further Posttranslational Protein Modifications

17.6.1 Insulin biosynthesis involves partial proteolysis.17.6.2 Proteolysis leads to zymogen activation.

17.6.2.1 Amino acids can be modified after incorporation into proteins.

See Table 17.10.17.6.3 Collagen biosynthesis requires many posttranslational modifications.

17.6.3.1 Procollagem formation occurs in the endoplasmic reticulum andGolgi appartus.

17.6.3.2 Collagen maturation occurs extracellularly.

17.7 Regulation of Translation

17.8 Protein Degradation and Turnover17.8.1 Intracelluar digestion of some proteins occurs in lysosomes.

17.8.2 Ubiquitin is a marker for an ATP-dependent proteolysis.


cc 17.1 Missense Mutation: Hemoglobincc 17.2 Disorders of Terminator Codons

cc 17.3 Thalassemia

cc 17.4 Mutation in Mitochondrial Ribosomal RNA Results in Antibiotic-Induced Deafness

cc 17.5 I Cell Disease

cc 17.6 Familial Hyperproinsulinemia

cc 17.7 Absence of Posttranslational Modification: Multiple Sulfatase Deficiency

cc 17.8 .Defects in Collagen Synthesis


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cc 17.9 Deletion of a Codon, Incorrect Posttranslational Modification, and Premature Protein

Degradation: Cystic Fibrosis

Chapter18 Recombinant DNA and Biotechnology

18.1 OverviewSophisticated techniques that will be increasingly used in medicine.18.2 The Polymerase Chain Reaction

18.2.1 Gives rapid production of large amounts of DNA from minute starting

substrate.

18.3 Restriction Endonuclease and Restriction Maps18.3.1 Restriction endonucleases permit selective hydrolysis of DNA to

genomic restriction maps.

18.3.2 Restriction maps permit the routine preparation of defined seqments ofDNA.

18.4 DNA Sequencing

18.4.1 Chemical cleavage method: Maxam-Gilbert procedure18.4.2 Interrupted enzymatic synthesis method: Sanger procedure.18.5 Recombinant DNA and Cloning

18.5.1 DNA from different sources can be ligated to form a new DNA

species: recombinant DNA.18.5.2 Recombinant DNA vectors can be produced in significant quantities by

cloning.18.5.3 DNA can be inserted into vector DNA in a specific direction:

directional cloning.18.5.4 Bacteria can be transformed with recombinant DNA.

18.5.5 It is necessary to be able to select transformed bacteria.

18.5.6 Recombinanat DNA molecules in a gene library.18.5.7 PCR may circumvent the need to clone DNA.

18.6 Selection of Specific Cloned DNA in Libraries18.6.1 Loss of antibiotic resistance is used to select transformed bacteria.

18.6.2 -Complementation for selecting bacteria carrying recombinant

plasmids.

18.7 Techniques for Detection and Identification of Nucleic Acids18.7.1 Nucleic acids can serve as probes for specific DNA or RNA sequences.

18.7.2 Southern blot technique is useful for identifying DNA fragments.18.7.3 Single-strand conformation polymorphism.

18.8 Complementary DNA and Complementary DNA Libraries

18.8.1 mRNA is used as a template for DNA synthesis using reversetranscriptase.18.8.2 Desired mRNA is a sample can be enriched by separation techniques.

18.8.3 Complementary DNA synthesis.

18.8.4 Total cellular RNA may be used as a template for DNSA synthesisusing RT-PCR.

18.9 Bacteriophage, Cosmid, and Yeast Cloning Vectors


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18.9.1 Bacteriophage as cloning vectors.

18.9.2 Screening bacteriophage libraries.18.9.3 Cloning DNA fragments into cosmid and yeast artificial chromosome

vectors.18.10 Techniques to Further Analyze Long Stretches of DNA

18.10.1 Subcloning permits definition of large segments of DNA.18.10.2 Chromosome walking is a technique to define gene arrangement inlong stretches of DNA.

18.11 Expression Vectors and Fusion Proteins

18.11.1 Foreign genes can be expressed in bacteria allowing synthesis of their

encoded proteins.18.12 Expression Vectors in Eukaryotic Cells

18.12.1 DNA elements required for expression of vectors in mammalian cells.

18.12.2 Transfected eukaryotic cells can be selected by utilizing mutant cellsthat require specific nutrients.

18.12.3 Foreign genes can be expressed in eukaryotic cells by utilizing virus

transformed cells.18.13 Site Directed Mutagenesis18.13.1 Role of flanking regions in DNA can be evaluated by deletion and

insertion mutations.

18.13.2 Site-directed mutagenesis of a single nucleotide.18.14 Applications of Recombinant DNA Technologies

18.14.1 Antisense nucleic acids hold promise as research tools and in therapy18.14.2 Normal genes can be introduced into cells with a defective gene in

gene therapy.18.14.3 Transgenic animals

18.14.4 Recombinant DNA in agricultural will have significant commercial

impact.18.15 Concluding Remarks


cc 18.1Polymerase Chain Reaction and Screening for Human Immunodeficiency Virus

cc 18.2 Restriction Mapping and Evolution

cc 18.3 Direct Sequencing of DNA for Diagnosis of Genetic Disorders

cc 18.4 Multiplex PCR Analysis of HGPRTase Gene Defects in Lesch-Nyhan Syndrome

cc 18.5 Restriction Fragment Length Polymorphisms Determine the Clonal Origin of Tumors

cc 18.6 Site-Directed Mutagenesis of HSV IgD

cc 18.7 Normal Genes Can be Introduced into Cells with Defective Genes in Gene Therapy

cc 18.8 Transgenic Animal Models

Chapter 19 Regulation of Gene Expression

19.1 Overview

19.2 Unit of Transcription in Bacteria: The Operon19.2.1 Partial genetic map ofE. coli. See fig. 19.1.

19.3 Lactose Operon ofE. coli


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19.3.1 Repressor of the lactose operon is a diffusible protein.

19.3.2 Operator sequence of the lactose operon is contiguous on DNA with apromoter and three structural genes. See Fig. 19.4.

19.3.3 Promoter sequence of lactose operon contains recognition sites forRNA polymerase and a regulator protein.

19.3.4 Catabolite activator protein binds at a site on the lactose promotor.19.4 Tryptophan Operon ofE. coli19.4.1 The tryptophan operon is controlled by a repressor protein.

19.4.2 The tryptophan operon has a second control site: the attenuator site.

19.4.3 Transcription attenuation is a mechanism of control in operons for

amino acid biosynthesis.19.5 Other Bacterial Operons

19.5.1 Synthesis of ribosomal proteins is regulated in a coordinated manner.

19.5.2 The stringent response controls synthesis of rRNAs and tRNAs.19.6 Bacterial Transposons

19.6.1 Transposons are mobile segments of DNA.

19.6.2 TheTn

3 transposon contains three structural genes.19.7 Inversion of Genes in Salmonella19.8 Organization of Genes in Mammalian DNA

19.8.1 Only a small fraction of eukaryotic DNA codes for proteins.

19.8.2 Eukaryotic genes usually contain interventing sequences (introns).19.9 Repetitive DNA Sequences in Eukaryotes

19.9.1 The importance of highly repetitive sequences is unknown.19.9.2 A variety of repeating units are defined as moderately repetitive

sequences.19.10 Genes for Globin Proteins

19.10.1 Recombinant DNA technology has been used to clone genes for

many eukaryotic processes.19.10.2 Sickle cell anemia is due to a single base pair change.19.10.3 Thalassemias are caused by mutations in genes for the or subunits

of globin.19.11 Genes for Human Growth Hormone-like Proteins

19.12 Mitochondrial Genes. See Fig. 19.27.

19.13 Bacterial Expression of Foreign Genes19.13.1 Recombinant bacteria can synthesize human insulin.

19.13.2 Recombinant bacteria can synthesis human growth hormone.19.14 Introduction of Rat Growth Hormone Gene into Mice


cc 19.1 Transmissible Multiple Drug Resistances

cc 19.2 Duchenne/Becker Muscular Dystrophy and the Dystrophin Gene

cc 19.3 Prenatal Diagnosis of Sickle Cell Anemia

cc 19.4 Prenatal Diagnosis of Thalassemia

cc 19.5 Leber Hereditary Optic Neuropathy (LHON)

cc 19.6 Huntington Disease and Unstable Trinucleotide Expansions


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Chapter 20 Biochemistry of Hormones I: Polypeptide

Hormones

20.1 Overview

20.1.1 Hormones bind to their cognate receptor.

20.1.2 There are peptide, amino acid, and steroid hormones.20.1.3 The signals of many hormones are amplified by a cascade system

involving second messengers.

20.2 Hormones and the Hormonal Cascade System20.2.1 A cascade amplification system is shown in Fig. 20.2

20.2.1.1 Hypthalmic interrelationships are shown in Fig. 20.3.20.2.2 Polypeptide hormones of the anterior pituitary are shown in Fig. 20.4.

20.3 Major Polypeptide Hormones and Their Actions20.3.1 Table 20.2 summaries the important polypeptide hormones.

20.4 Genes and Formation of Polypeptide Hormones

20.4.1 Propiomelanocortin is a precursor polypeptide for eight hormones.

See. Fig. 20.5.

20.4.2 Many polypeptide hormones are encoded together in a single gene.20.4.3 Multiple copies of a hormone can be encoded on a single gene.

20.5 Synthesis of Amino Acid-Derived Hormones

20.5.1 Epinephrine is synthesized from phenylalanine/tyrosine.20.5.2 The synthesis of thyroid hormone requires incorporation of iodine into

a tyrosine of thyroglobulin.

20.6 Inactivation and Degradation of Hormones

20.7 Cell Regulation and Hormone Secretion20.7.1 G-proteins serve as cellular transducers of hormone signals. See Fig.

20.17.

20.7.2 cAMP activates a protein kinase a pathway.20.7.3 Inositiol triphosphate formation leads to release of calcium from

intracellular stores.20.7.4 Diacylglycerol activates protein kinase C pathway.

20.8 Cyclic Hormonal Cascade Systems20.8.1 Melatonin and serotonin synthesis are controlled by light and dark

cycles20.8.2 The ovarian cycle is controlled by gonadotropin-releasing hormone.

20.8.2.1 Absence of fertilization.

20.8.3 Fertilization20.9 Hormone-Receptor Interactions

20.9.1 Scatchard analysis permits determination of the number of receptor-binding sites and association constant for ligand.

20.9.2 Some hormone-receptor interactions involve multiple hormonesubunits.

20.10 Structure of Receptors: -Adrenergic Receptor20.11 Internalization of Receptors

20.11.1 Clathrin forms a lattice structure to direct internalization ofhormone-receptor complexes from the plasma membrane.


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20.12 Intracellular Action: Protein Kinases

20.12.1 Insulin receptor: transduction through tyrosine kinase20.12.2 Activity of vasopressin: protein kinase A.

20.12.3 Gonadotropin-releasing hormone (GnRH): Protein kinase C20.12.4 Activity of atrial natriuretic factor (ANF): protein kinase G.

20.13 Oncogenes and Receptor Functions20.13.1 The known oncogenes are summarized in Table 20.9.


cc 20.1 Testing Activity of the Anterior Pituitary

cc 20.2 Hypopituitarism

cc 20.3 Lithium Treatment of Manic Depressive Illness: The Phosphatidylinositol Cycle

Chapter 21 Biochemistry of Hormones II: Steroid Hormones

21.1 Overview21.2 Structures of Steroid Hormones

21.2.1 The major steroid hormones of humans are listed in Table 21.1.21.3 Biosynthesis of Steroid Hormones

21.3.1 Steroid hormones are synthesized from cholesterol.

21.4 Metabolic Inactivation of Steroid Hormones

21.5 Cell-Cell Communication and Control of Synthesis and Release of SteroidHormones

21.5.1. Steroid hormone synthesis is controlled by specific hormones.

21.5.1.1 Aldosterone.21.5.1.2 Estradiol

21.5.1.3 Vitamin D321.6 Transport of Steroid Hormones in Blood

21.6.1 Steroid hormones are bound to specific proteins or albumin in blood.21.7 Steroid Hormone Receptors

21.7.1 Steroid hormones bind to specific intracellular protein receptors.

21.7.2 Some steroid receptors are part of the cErbA family of proto-

oncogenes.

21.8 Receptor Activation: Upregulation and Downregulation21.8.1 Steroid receptors can be upregulated or downregulated depending

on exposure to hormone.

21.9 A Specific Example of Steroid Hormone Action at Cell Level: Programmed

Death


cc 21.1 Oral Contraception

cc 21.2 Apparent Mineralocorticoid Excess Syndrome

cc 21.3 Programmed Cell Death in the Ovarian Cycle


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Chapter 22 Molecular Cell Biology

22.1 Overview22.2 Nervous Tissue: Metabolism and Function

22.2.1 ATP and transmembrane electrical potential in neurons.

22.2.2 Neuron-neuron interaction occurs through synapses.22.2.3 Synthesis, storage, and release of neurotransmitters.

22.2.3.1 Listed in Table 22.1.

22.2.3.2 Proteins listed in Table 22.2

22.3.4 Termination of signals at synaptic junctions.22.3.4.1 Acetylcholine

22.3.4.2 Catecholamines

22.3.4.3 Serotonin (5-hydroxytryptamine)22.3.4.4 4-Aminobutyrate

22.3.5. Neuropeptides are derived from precursor proteins.22.3 The Eye: Metabolism and Vision

22.3.1 The cornea derives ATP from aerobic metabolism.22.3.2 Lens consists mostly of water and proteins.

22.3.3 The retina derives ATP from anaerobic glycolysis.22.3.4 Visual transduction involves photochemical, biochemical, and electric

events.22.3.4.1 The biochemical events of the visual cycle are shown in Fig.

22.24.

22.3.5 Photoreceptor cells are rods and cones.

22.3.6 Color vision originates in the cones.

22.3.7 Other physical and chemical differences between rods and cones.22.4 Muscle Contraction

22.4.1 Skeletal muscle contraction follows an electrical to chemical tomechanical path.22.4.2 Myosin forms the thick filament of muscle.

22.4.3 Actin, tropomyosin, and troponin are thin filament proteins.

22.4.4 Muscle contraction requires Ca2+ interaction.

22.4.5 Energy for muscle contraction is supplied by ATP hydrolysis.22.4.6 Model for skeletal muscle contraction is shown in Fig. 22.34.

22.4.7 Calcium regulates smooth muscle contraction.

22.5 Mechanism of Blood Coagulation22.5.1 Clot formation is a membrane-mediated process.

22.5.2 Reactions of the intrinsic pathway.

22.5.3 Reactions of the extrinsic pathway.22.5.4 Thrombin converts fibrinogen to fibrin.22.5.5 Major roles of thrombin.

22.5.6 Formation of a platelet plug.22.5.7 Properties of some of the proteins involved in coagulation.

22.5.8 Role of vitamin K in protein carboxylase reactions.

22.5.9 Control of the synthesis of Gla-proteins.22.5.10 Dual role of thrombin in promoting coagulation and clot dissolution.


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22.5.11 The allosteric role of thrombin in controlling coagulation.

22.5.12 Inhibitors of the plasma serineproteinases.22.5.13 Fibrinolysis requires plaminogen and tissue plasminogen activator to

produce plasmin.


cc 22.1 Lambert Eaton Myasthenic Syndrome

cc 22.2 Myasthenia Gravis: A Neuromuscular Disorder

cc 22.3 Macula Degeneration Other Causes of Loss of Vision

cc 22.4 Niemann Pick Disease and Retinitis Pigmentosa

cc 22.5 Retinitis Pigmentosa Resulting from a de Novo Mutation in the Gene Codingfor

Peripherin

cc 22.6 Chromosomal Location of Genes for Vision

cc 22.7 Troponin Subunits as Markers for Myocardial Infarction

cc 22.8 Voltage Gated Ion Channelopathies

cc 22.9 Intrinsic Pathway Defects Prekallikrein Deficiency

cc 22.10 Classic Hemophilia

cc 22.11 Thrombosis and Defects of the Protein C Pathw

Chapter 23 Biotransformations: The Cytochromes P450

23.1 Overview23.1.1 A family of heme proteins.

23.2 Cytochrome P450: Nomenclature and Overall Reaction23.2.1 Endoplasmic reticulum or microsomes.

23.3 Cytochrome P450: Multiple Forms23.3.1 Multiplicity of genes produces many forms of cytochrome P450.

23.3.1.1 Substrate specificity

23.3.1.2 Induction of cytochrome P45023.3.1.3 Polymorphisms.

23.4 Inhibitors of Cytochrome P45023.5 Cytochrome P450 Electron Transport Systems

23.5.1 NADH-adrenodoxin reductase is the flavoprotein donor in

mitochondria.

23.6 Physiological Functions of Cytochromes P45023.6.1 Cytochrome P450 participate in synthesis of steroid hormones and

oxygenation of eicosanoids.

23.6.2 Cytochrome P450 oxidize exogenous lipophilic substrates.23.7 Other Hemoprotein and Flavoprotein-Mediated Oxygenations: The Nitric

Oxide Synthases23.7.1 Three distinct nitric oxide synthase gene products display diverse

physiological functions.23.7.2 Structural aspects of nitric oxide synthases.


cc 23.1 Consequences of Induction of Drug Metabolizing Enzymes

cc 23.2 Genetic Polymorphisms of Drug-Metabolizing Enzymes


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cc 23.3 Deficiency of Cytochrome P450 21 Hydroxylase

cc 23.4 Steroid Hormone Production During Pregnancy

cc 23.5 Clinical Aspects of Nitric Oxide Production

Chapter 24 Iron and Heme Metabolism

24.1 Iron Metabolism: Overview

24.1.1 Two oxidation state 2+ and 3+.

24.2 Iron-Containing Proteins24.2.2 Transferrin transports iron in serum

24.2.3 Lactoferrin binds iron in milk.

24.2.4 Ferritin is a protein involved in the storage of iron.24.2.5 Other nonheme iron-containing proteins are involved in enzymatic

processes.

24.3 Intestinal Absorption of Iron

24.3.1 Major site is the small intestines.24.4 Molecular Regulation of Iron Utilization

24.4.1 Iron regulatory proteins.

24.4.2 stem-loop structure24.5 Iron Distribution and Kinetics

24.6 Heme Biosynthesis24.6.1 Enzymes in heme biosynthesis occur in both mitochondria and cytosol

24.6.1 Aminolevulinic acid synthase24.6.2 ALA dehydratase

24.6.3 Porphobilinogen deaminase24.6.4 Uroporphyrinogen decarboxylase.

24.6.5 Coproporphyrinogen oxidase.

24.6.6 Protoporphyrinogen oxidase.24.6.7 Ferochelatase

24.6.2 ALA synthase catalyzes the rate-limiting step of heme biosynthesis.

24.7 Heme Catabolism

24.7.1 Bilirubin is conjugated to form bilirubin diglucuronide in liver. SeeFig. 24.13.

24.7.2 Intravascular hemolysis requires scavenging of iron.


cc 24.1 Iron Overload and Infection

cc 24.2 Duodenal Iron Absorption

cc 24.3 Mutant Iron-Responsive Elementcc 24.4 Ceruloplasmin Deficiency

cc 24.5 Iron-Deficiency Anemia

cc 24.6 Hemochromatosis and Iron-Fortified Diet

cc 24.7 Acute Intermittent Porphyria

cc 24.8 Neonatal Isoimmune Hemolysis

cc 24.9 Bilirubin UDP-Glucuronosyltransferase Deficiency

cc 24.10 Elevation of Serum Conjugated Bilirubin


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Chapter 25 Gas Transport and pH Regulation

25.1 Introduction to Gas Transport

25.2 Need for a Carrier of Oxygen in the Blood

25.2.1 Respiratory system anatomy affects blood gas concentration.25.2.2 A physiological oxygen crrier must have unusual properties.

25.2.3 The steep part of the curve lies in the physiological range.

25.3 Hemoglobin and Allosterism: Effect of 2,3 Bisphosphoglycerate

25.4 Other Hemoglobins25.5 Physical Factors that Affect Oxygen Binding

25.5.1 High temperature weakens hemoglobins oxygen affinity.

25.5.2 Low pH weakens hemoglobins oxygen affinity.25.6 Carbon Dioxide Transport

25.6.1 Blood CO2 is present in three major forms.25.6.2 Bicarbonate formation.

25.6.3 Carbaminohemoglobin formation.25.6.4 Two processes regulate [H+] derived from CO2 transport.

25.6.4.1 Buffering25.6.4.2Isohydric mechanism

25.6.5 HCO3- distribution between plasma and erythrocytes.

25.7 Interrelationships Among Hemoglobin, Oxygen, Carbon Dioxide,Hydrogen Ion, and 2,3 Bisphosphoglycerate

25.8 Introduction to pH Regulation

25.9 Buffer Systems of Plasma, Interstitial Fluid, and Cells

25.10 The Carbon Dioxide-Bicarbonate Buffer System25.10.1 The chemistry of the system

25.10.2 The carbon dioxide-bicarbonate buffer system is an open system.25.10.3 Graphical representation: the pH-bicarbonate diagram. See Fig. 25.18.

25.11 Acid-Base Balance and Its Maintenance

25.11.1 The kidney plays a critical role in acid-base balance.

25.11.2 Urine formation occurs primarily in the nephron.

25.11.3 The three fates of excreted H+.25.11.4 Total acidity of the urine.

25.12 Compensatory Mechanisms

25.12.1 Principles of compensation.25.12.1.1The three states of compensation defined

1.2.7.1.1 Compensated.1.2.7.1.2 Uncompensated1.2.7.1.3 Partially compensated.

1.2.8 Specidic compensatory processes1.2.8.1Respiratory acidosis.1.2.8.2Respiratory alkalosis.1.2.8.3Metabolic acidosis.1.2.8.4Metabolic alkalosis

1.3Alternative Measures of Acid-Base Imbalance


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26.5.1 Do- and polysaccharides require hydrolysis.

26.5.2 Monosaccharides are absorbed by carrier-mediated transport.26.6 Digestion and Absorption of Lipids

26.6.1 Lipid digestion requires overcoming the limited water solubility oflipids.

26.6.2 Lipids are digested by gastric and pancreatic lipases.26.6.3 Bile acid micelles solubilize lipids during digestion.26.6.4 Most absorbed lipids are incorporated into chylomicrons

26.7 Bile Acid Metabolism


cc 26.1 Cystic Fibrosis

cc 26.2 Bacterial Toxigenic Diarrheas and Electrolyte Replacement Therapy

cc 26.3 Neutral Amino Aciduria (Hartnup Disease)

cc 26.4 Disaccharidase Deficiency

cc 26.5 Cholesterol Stones

cc 26.6 A--Lipoproteinemia

Chapter 27 Principles of Nutrition I: Macronutrients

27.1 Overview

27.1.1 Under nutrition

27.1.2 Over nutrition27.1.3 Optimal nutrition

27.2 Energy Metabolism

27.2.1 The energy content of food is measured in kilocalories.

27.2.2 The energy expenditure is influenced by four factors.

27.2.2.1 Surface area27.2.2.2 Age

27.2.2.3 Sex27.2.2.4 Activity level

27.3 Protein Metabolism27.3.1 Dietary protein serves many roles including energy production.

27.3.2 Nitrogen balance relates intake of nitrogen to its excretion.27.3.3 Essential amino acids must be present in the diet.27.3.4 Protein sparing is related to the dietary content of carbohydrate and fat.

27.3.5 Normal adult protein requirements depend on diet.

27.3.5.1 0.8 g/kg per day 58 g for a 160-lb man.

27.3.6 Protein requirement increases during growth and recovery from illness.27.4 Protein-Energy Malnutrition

27.5 Excess Protein-Energy Intake

27.5.1 Obesity has dietary and genetic components.27.5.2 Metabolic consequences of obesity have significant health

implications.

27.6 Carbohydrates

27.7 Fats


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27.8 Fiber

27.9 Composition of Macronutrients in the Diet27.9.1 Composition of the diet affect serum cholesterol.

27.9.2 Effects of refined carbohydrate in the diet are not straightforward.27.9.3 Mixed vegetable and animal proteins meet nutritional protein

requirements.27.9.4 An increase in fiber from varied sources is desirable.27.9.5 Current recommendations are for a prudent diet. See Fig. 27.3.


cc 27.1 Vegetarian Diets and Protein-Energy Requirements

cc 27.2 Low-Protein Diets and Renal Disease

cc 27.3 Providing Adequate Protein and Calories for the Hospitalized Patient

cc 27.4 Carbohydrate Loading and Athletic Endurance

cc 27.5 High-Carbohydrate versus High-Fat Diets for Diabetics

cc 27.6 Polyunsaturated Fatty Acids and Risk Factors for Heart Disease

cc 27.7 Metabolic Adaptation: The Relationship between Carbohydrate Intake and Serum

Triacylglycerols

Chapter 28 Principles of Nutrition II: Micronutrients

28.1 Overview

28.1.1 Micronutrients are important.

28.2 Assessment of Malnutrition

28.2.1 Dietary intake studies.28.2.2 Biochemical assays.

28.2.3 Clinical symptoms

28.3 Recommended Dietary Allowances28.3.1 Ideal average

28.3.2 Healthy people28.3.3 Knowledge is changing.

28.3.4 Optimal levels not defined.28.4 Fat-Soluble Vitamins

28.4.1 Vitamin A is derived from plant carotenoids.28.4.2 Vitamin D synthesis in the body requires sunlight.

28.4.3 Vitamin E is a mixture of tocopherols.

28.4.4 Vitamin K is a quinone derivative.28.5 Water-Soluble Vitamins

28.6 Energy-Releasing Water-Soluble Vitamins28.6.1 Thiamine (vitamin B1) forms the coenzyme TPP (thiamine

pyrophosphate).28.6.2 Riboflavin is part of FAD and FMN.

28.6.3 Niacin is part of NAD+ and NADP+.

28.6.4 Pyridoxine (vitamin B6) forms the coenzyme pyridoxal phosphate.28.6.5 Pantothenic acid and biotin are also energy-releasing vitamins

28.7 Hematopoietic Water-Soluble Vitamins


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28.7.1 Folic acid functions as tetrahydrofolate in one-carbon metabolism.

28.7.2 Vitamin B12 (cobalamine) contains cobalt in a tetrapyrrole ring.28.8 Other Water-Soluble Vitamins

28.8.1 Ascorbic acid functions in reduction and hydroxylation reactions.28.8.2 Lipoic acid function in -keto acid metabolism.

28.9 Macrominerals28.9.1 Calcium has many physiological roles.

28.9.2 Magnesium is another important macromineral.28.10 Trace Minerals

28.10.1 Iron is efficiently reutilized.

28.10.2 Iodine is incorporated into thyroid hormones.

28.10.3 Zinc is a cofactor for many enzymes.28.10.4 Copper is also a cofactor for important enzymes.28.10.5 Chromium is a component of glucose tolerance factor.

28.10.6 Selenium is a scavenger of peroxides.28.10.7 Manganese, molybdenum, fluoride, and boron are other trace

elements.28.11 The American Diet: Fact and Fallacy

28.12 Assessment of Nutritional Status in Clinical Practice


cc 28.1 Nutritional Considerations for Cystic Fibrosis

cc 28.2 Renal Osteodystrophy

cc 28.3 Nutritional Considerations in the born

cc 28.4 Anticonvulsant Drugs and Vitamin Requirements

cc 28.5 Nutritional Considerations in the Alcoholic

cc 28.6 Vitamin B6 Requirements for Users of Oral Contraceptives

cc 28.7 Diet and Osteoporosis

cc 28.8 Nutritional Considerations for Vegetarianscc 28.9 Nutritional Needs of Elderly Persons

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