Principles of Medical Biochemistry - 4th Edition - ISBN: 9780323296168, 9780323391917

Principles of Medical Biochemistry

4th Edition

Authors: Gerhard Meisenberg William Simmons
eBook ISBN: 9780323391917
eBook ISBN: 9780323391863
eBook ISBN: 9780323391900
eBook ISBN: 9780323391870
eBook ISBN: 9780323391894
Paperback ISBN: 9780323296168
Imprint: Elsevier
Published Date: 28th November 2016
Page Count: 657
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Description

For nearly 30 years, Principles of Medical Biochemistry has integrated medical biochemistry with molecular genetics, cell biology, and genetics to provide complete yet concise coverage that links biochemistry with clinical medicine. The 4th Edition of this award-winning text by Drs. Gerhard Meisenberg and William H. Simmons has been fully updated with new clinical examples, expanded coverage of recent changes in the field, and many new case studies online. A highly visual format helps readers retain complex information, and USMLE-style questions (in print and online) assist with exam preparation.

Key Features

  • Just the right amount of detail on biochemistry, cell biology, and genetics – in one easy-to-digest textbook.
  • Full-color illustrations and tables throughout help students master challenging concepts more easily.
  • Online case studies serve as a self-assessment and review tool before exams.
  • Glossary of technical terms, both in print and online.

Table of Contents

Part ONE

PRINCIPLES OF MOLECULAR STRUCTURE AND

FUNCTION 1

Chapter 1

INTRODUCTION TO BIOMOLECULES

Water Is the Solvent of Life

Water Contains Hydronium Ions and Hydroxyl Ions

Ionizable Groups Are Characterized by Their pK Values

The Blood pH is Tightly Regulated

Acidosis and Alkalosis Are Common in Clinical Practice

Bonds Are Formed by Reactions between Functional Groups

Isomeric Forms Are Common in Biomolecules

Properties of Biomolecules Are Determined by Their Noncovalent

Interactions

Triglycerides Consist of Fatty Acids and Glycerol

Monosaccharides Are Polyalcohols with a Keto Group or an

Aldehyde Group

Monosaccharides Form Ring Structures

Complex Carbohydrates Are Formed by Glycosidic Bonds

Polypeptides Are Formed from Amino Acids

Nucleic Acids Are Formed from Nucleotides

Most Biomolecules Are Polymers

Summary

Chapter 2

INTRODUCTION TO PROTEIN STRUCTURE

Amino Acids Are Zwitterions

Amino Acid Side Chains Form Many Noncovalent

Interactions

Peptide Bonds and Disulfide Bonds Form the Primary Structure of

Proteins

Proteins Can Fold Themselves into Many Shapes

α-Helix and β-Pleated Sheet Are the Most Common Secondary

Structures in Proteins

Globular Proteins Have a Hydrophobic Core

Proteins Lose Their Biological Activities When Their Higher-Order

Structure Is Destroyed

The Solubility of Proteins Depends on pH and Salt

Concentration

Proteins Absorb Ultraviolet Radiation

Proteins Can Be Separated by Their Charge or Their Molecular

Weight

Abnormal Protein Aggregates Can Cause Disease

Neurodegenerative Diseases Are Caused by Protein Aggregates

Protein Misfolding Can Be Contagious

Summary

Chapter 3

OXYGEN TRANSPORTERS: HEMOGLOBIN AND

MYOGLOBIN

The Heme Group Is the Oxygen-Binding Site of Hemoglobin and

Myoglobin

Myoglobin Is a Tightly Packed Globular Protein

Red Blood Cells Are Specialized for Oxygen Transport

The Hemoglobins Are Tetrameric Proteins

Oxygenated and Deoxygenated Hemoglobin Have Different

Quaternary Structures

Oxygen Binding to Hemoglobin Is Cooperative

2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of

Oxygen Binding to Hemoglobin

Fetal Hemoglobin Has a Higher Oxygen-Binding Affinity than

Does Adult Hemoglobin

The Bohr Effect Facilitates Oxygen Delivery

Most Carbon Dioxide Is Transported as Bicarbonate

Summary 38

Chapter 4

ENZYMATIC REACTIONS 39

The Equilibrium Constant Describes the Equilibrium of the

Reaction

The Free Energy Change Is the Driving Force for Chemical

Reactions

The Standard Free Energy Change Determines the Equilibrium

Enzymes Are Both Powerful and Selective

The Substrate Must Bind to Its Enzyme before the Reaction Can

Proceed

Rate Constants Are Useful for Describing Reaction Rates

Enzymes Decrease the Free Energy of Activation

Many Enzymatic Reactions Can Be Described by Michaelis-Menten

Kinetics

Km and Vmax Can Be Determined Graphically

Substrate Half-Life Can Be Determined for First-Order but Not

Zero-Order Reactions

Kcat/Km Predicts the Enzyme Activity at Low Substrate

Concentration

Allosteric Enzymes Do Not Conform to Michaelis-Menten

Kinetics

Enzyme Activity Depends on Temperature and pH

Different Types of Reversible Enzyme Inhibition Can Be

Distinguished Kinetically

Enzymes Stabilize the Transition State

Chymotrypsin Forms a Transient Covalent Bond during

Catalysis

Summary

Chapter 5

COENZYMES

Enzymes Are Classified According to Their Reaction Type

Adenosine Triphosphate Has Two Energy-Rich Bonds

ATP Is the Phosphate Donor in Phosphorylation Reactions

ATP Hydrolysis Drives Endergonic Reactions

Cells Always Try to Maintain a High Energy Charge

Dehydrogenase Reactions Require Specialized Coenzymes

Coenzyme A Activates Organic Acids

S-Adenosyl Methionine Donates Methyl Groups

Many Enzymes Require a Metal Ion

Summary

Part TWO

GENETIC INFORMATION: DNA, RNA, AND

PROTEIN SYNTHESIS

Chapter 6

DNA, RNA, AND PROTEIN SYNTHESIS

All Living Organisms Use DNA as Their Genetic Databank

DNA Contains Four Bases

DNA Forms a Double Helix

DNA Can Be Denatured

DNA Is Supercoiled

DNA Replication Is Semiconservative

DNA Is Synthesized by DNA Polymerases

DNA Polymerases Have Exonuclease Activities

Unwinding Proteins Present a Single-Stranded Template to the

DNA Polymerases

One of the New DNA Strands Is Synthesized Discontinuously

RNA Plays Key Roles in Gene Expression

The Σ Subunit Recognizes Promoters

DNA Is Faithfully Copied into RNA

Some RNAs Are Chemically Modified after Transcription

The Genetic Code Defines the Structural Relationship between mRNA and Polypeptide

Transfer RNA Is the Adapter Molecule in Protein Synthesis

Amino Acids Are Activated by an Ester Bond with the 3ˈ Terminus

of the tRNA

Many Transfer RNAs Recognize More than One Codon

Ribosomes Are the Workbenches for Protein Synthesis

The Initiation Complex Brings Together Ribosome, Messenger

RNA, and Initiator tRNA

Polypeptides Grow Stepwise from the Amino Terminus to the

Carboxyl Terminus

Protein Synthesis Is Energetically Expensive

Gene Expression Is Tightly Regulated

A Repressor Protein Regulates Transcription of the lac Operon

in E. coli

Anabolic Operons Are Repressed by the End Product of the

Pathway

Glucose Regulates the Transcription of Many Catabolic

Operons

Transcriptional Regulation Depends on DNA-Binding

Proteins

Summary

Chapter 7

THE HUMAN GENOME

Chromatin Consists of DNA and Histones

The Nucleosome Is the Structural Unit of Chromatin

Covalent Histone Modifications Regulate DNA Replication and

Transcription

DNA Methylation Silences Genes

All Eukaryotic Chromosomes Have a Centromere, Telomeres, and

Replication Origins

Telomerase Is Required (but Not Sufficient) for Immortality

Eukaryotic DNA Replication Requires Three DNA

Polymerases

Most Human DNA Does Not Code for Proteins

Gene Families Originate by Gene Duplication

The Genome Contains Many Tandem Repeats

Some DNA Sequences Are Copies of Functional RNAs

Many Repetitive DNA Sequences Are (or Were) Mobile

L1 Elements Encode a Reverse Transcriptase

Alu Sequences Spread with the Help of L1 Reverse

Transcriptase

Mobile Elements Are Dangerous

Humans Have Approximately 20,000 Genes

Transcriptional Initiation Requires General Transcription

Factors

Genes Are Surrounded by Regulatory Sites

Gene Expression Is Regulated by DNA-Binding Proteins

Long Non-coding RNAs Play Roles in Gene Expression

mRNA Processing Starts during Transcription

Translational Initiation Requires Many Initiation Factors

mRNA Processing and Translation Are Often Regulated

Small RNA Molecules Inhibit Gene Expression

Mitochondria Have Their Own DNA

Human Genomes Are Very Diverse

Human Genomes Have Many Low-Frequency Copy Number

Variations

Summary

Chapter 8

PROTEIN TARGETING AND PROTEOSTASIS

A Signal Sequence Directs Polypeptides to the Endoplasmic

Reticulum

Glycoproteins Are Processed in the Secretory Pathway

The Endocytic Pathway Brings Proteins into the Cell

Lysosomes Are Organelles of Intracellular Digestion

Autophagy Recycles Cellular Proteins and Organelles

Poorly Folded Proteins Are Either Repaired or Destroyed

Ubiquitin Markes Proteins for Destruction

The Proteostatic System Protects Cells from Abnormal Proteins

Summary

Chapter 9

INTRODUCTION TO GENETIC DISEASES

Four Types of Genetic Disease

Mutations Occur in the Germline and in Somatic Cells

Mutations Are an Important Cause of Poor Health

Small Mutations Lead to Abnormal Proteins

Most Mutations Are Caused by Replication Errors

Mutations Can Be Induced by Radiation and Chemicals

Mismatch Repair Corrects Replication Errors

Missing Bases and Abnormal Bases Need to Be Replaced

Nucleotide Excision Repair Removes Bulky Lesions

Repair of DNA Double-Strand Breaks Is Difficult

Hemoglobin Genes Form Two Gene Clusters

Many Point Mutations in Hemoglobin Genes Are Known

Sickle Cell Disease Is Caused by a Point Mutation in the b-Chain

Gene

SA Heterozygotes Are Protected from Tropical Malaria

α-Thalassemia Is Most Often Caused by Large Deletions

Many Different Mutations Can Cause β-Thalassemia

Fetal Hemoglobin Protects from the Effects of β-Thalassemia and

Sickle Cell Disease

Summary

Chapter 10

VIRUSES

Viruses Can Replicate Only in a Host Cell

Bacteriophage T4 Destroys Its Host Cell

DNA Viruses Substitute Their Own DNA for the Host Cell

DNA

λ Phage Can Integrate Its DNA into the Host Cell

Chromosome

RNA Viruses Require an RNA-Dependent RNA Polymerase

Retroviruses Replicate Through a DNA Intermediate

Plasmids Are Small "Accessory Chromosomes" or "Symbiotic

Viruses" of Bacteria

Bacteria Can Exchange Genes by Transformation and

Transduction

Jumping Genes Can Change Their Position in the Genome

Summary

Chapter 11

DNA TECHNOLOGY

Restriction Endonucleases Cut Large DNA Molecules into Smaller

Fragments

Large Probes Are Used to Detect Copy Number Variations

Small Probes Are Used to Detect Point Mutations

Southern Blotting Determines the Size of Restriction

Fragments

DNA Can Be Amplified with the Polymerase Chain Reaction

PCR Is Used for Preimplantation Genetic Diagnosis

Allelic Heterogeneity Is the Greatest Challenge for Molecular

Genetic Diagnosis

Normal Polymorphisms Are Used as Genetic Markers

Tandem Repeats Are Used for DNA Fingerprinting

DNA Microarrays Can Be Used for Genetic Screening

DNA Microarrays Are Used for the Study of Gene Expression

DNA Is Sequenced by Controlled Chain Termination

Massively Parallel Sequencing Permits Cost-Efficient

Whole-Genome Genetic Diagnosis

Gene Therapy Targets Somatic Cells

Viruses Are Used as Vectors for Gene Therapy

Retroviruses Can Splice a Transgene into the Cell’s Genome

Genome Editing Is Based on the Making and Healing of DNA Double Strand Breaks

Designer Nucleases Are Used for Genome Editing

Antisense Oligonucleotides Can Block the Expression of Rogue

Genes

Genes Can Be Altered in Animals

Tissue-Specific Gene Expression Can Be Engineered into

Animals

Human Germline Genome Editing is Technically Possible

Summary

Part THREE

CELL AND TISSUE STRUCTURE

Chapter 12

BIOLOGICAL MEMBRANES

Membranes Consist of Lipid and Protein

Phosphoglycerides Are the Most Abundant Membrane Lipids

Most Sphingolipids Are Glycolipids

Cholesterol Is the Most Hydrophobic Membrane Lipid

Membrane Lipids Form a Bilayer

The Lipid Bilayer Is a Two-Dimensional Fluid

The Lipid Bilayer Is a Diffusion Barrier

Membranes Contain Integral and Peripheral Membrane

Proteins

Membranes Are Asymmetrical

Membranes Are Fragile

Membrane Proteins Carry Solutes across the Lipid Bilayer

Transport against an Electrochemical Gradient Requires Metabolic

Energy

Active Transport Consumes ATP

Sodium Cotransport Brings Molecules into the Cell

Summary

Chapter 13

THE CYTOSKELETON

The Erythrocyte Membrane Is Reinforced by a Spectrin

Network

Keratins Give Strength to Epithelia

Actin Filaments Are Formed from Globular Subunits

Striated Muscle Contains Thick and Thin Filaments

Myosin Is a Two-Headed Molecule with ATPase Activity

Muscle Contraction Requires Calcium and ATP

The Cytoskeleton of Skeletal Muscle Is Linked to the Extracellular

Matrix

Microtubules Consist of Tubulin

Eukaryotic Cilia and Flagella Contain a 9 + 2 Array of

Microtubules

Cells Form Specialized Junctions with Other Cells and with the

Extracellular Matrix

Summary

Chapter 14

THE EXTRACELLULAR MATRIX

Collagen Is the Most Abundant Protein in the Human Body

Tropocollagen Molecule Forms a Long Triple Helix

Collagen Fibrils Are Staggered Arrays of Tropocollagen

Molecules

Collagen Is Subject to Extensive Posttranslational Processing

Collagen Metabolism Is Altered in Aging and Disease

Many Genetic Defects of Collagen Structure and Biosynthesis Are

Known

Elastic Fibers Contain Elastin and Fibrillin

The Amorphous Ground Substance Contains Hyaluronic Acid

Sulfated Glycosaminoglycans Are Covalently Bound to Core

Proteins

Cartilage Contains Large Proteoglycan Aggregates

Proteoglycans Are Synthesized in the ER and Degraded in

Lysosomes

Mucopolysaccharidoses Are Caused by Deficiency of

Glycosaminoglycan-Degrading Enzymes

Bone Consists of Calcium Phosphates in a Collagenous

Matrix

Basement Membranes Contain Type IV Collagen, Laminin,

and Heparan Sulfate Proteoglycans

Fibronectin Glues Cells and Collagen Fibers Together

Summary

Part FOUR

MOLECULAR PHYSIOLOGY

Chapter 15

EXTRACELLULAR MESSENGERS

Steroid Hormones Are Made from Cholesterol

Progestins Are the Biosynthetic Precursors of All Other Steroid

Hormones

Thyroid Hormones Are Synthesized from Protein-Bound

Tyrosine

T4 Becomes Activiated to T3 in the Target Tissues

Both Hypothyroidism and Hyperthyroidism Are Common

Disorders

Insulin Is Released Together with the C-Peptide

Proopiomelanocortin Forms Several Active Products

Angiotensin Is Formed from Circulating Angiotensinogen

Immunoassays Are Used for Determination of Hormone Levels

Catecholamines Are Synthesized from Tyrosine

Indolamines Are Synthesized from Tryptophan

Histamine Is Produced by Mast Cells and Basophils

Neurotransmitters Are Released at Synapses

Acetylcholine Is the Neurotransmitter of the Neuromuscular

Junction

There Are Many Neurotransmitters

Summary

Chapter 16

INTRACELLULAR MESSENGERS

Receptor-Hormone Interactions Are Noncovalent, Reversible,

and Saturable

Many Neurotransmitter Receptors Are Ion Channels

Steroid and Thyroid Hormones Bind to Transcription Factors

Seven-Transmembrane Receptors Are Coupled to G Proteins

Adenylate Cyclase Is Regulated by G Proteins

Hormones Can Both Activate and Inhibit the cAMP Cascade

Cytoplasmic Calcium Is an Important Intracellular Signal

Phospholipase C Generates Two Second Messengers

Both cAMP and Calcium Regulate Gene Transcription

Muscle Contraction and Exocytosis Are Triggered by Calcium

Atrial Natriuretic Factor Acts through a Membrane-Bound Guanylate Cyclase

Nitric Oxide Stimulates a Soluble Guanylate Cyclase

cGMP Is a Second Messenger in Retinal Rod Cells

Receptors for Insulin and Growth Factors Are Tyrosine-Specific

Protein Kinases

Growth Factors and Insulin Trigger Multiple Signaling

Cascades

Cytokin Receptors Use the JAK-Stat Pathway

Many Receptors Become Desensitized after Overstimulation

Summary

Chapter 17

PLASMA PROTEINS

The Blood pH Is Tightly Regulated

Acidosis and Alkalosis Are Common in Clinical Practice

Plasma Proteins Are Both Synthesized and Destroyed in the

Liver

Albumin Prevents Edema

Albumin Binds Many Small Molecules

Some Plasma Proteins Are Specialized Carriers of Small

Molecules

Deficiency of α1-Antiprotease Causes Lung Emphysema

Levels of Plasma Proteins Are Affected by Many Diseases

Blood Components Are Used for Transfusions

Blood Clotting Must Be Tightly Controlled

Platelets Adhere to Exposed Subendothelial Tissue

Insoluble Fibrin Is Formed from Soluble Fibrinogen

Thrombin Is Derived from Prothrombin

Factor X Can Be Activated by the Extrinsic and Intrinsic

Pathways

Negative Controls Are Necessary to Prevent Thrombosis

Plasmin Degrades the Fibrin Clot

Heparin and the Vitamin K Antagonists Are Used as

Anticoagulants

Clotting Factor Deficiencies Cause Abnormal Bleeding

Tissue Damage Causes Release of Cellular Enzymes into

Blood

Serum Enzymes Are Used for the Diagnosis of Many Diseases

Summary

Chapter 18

Defense Mechanisms

Lipophilic Xenobiotics Are Metabolized to Water-soluble Products

Cytochrome P-450 Is Involved in Phase I Metabolism

Phase II Metabolism Makes Xenobiotics Water-Soluble for Excretion

Phase III Metabolism Excretes Xenobiotic Metabolites

Drug Metabolizing Enzymes Are Inducible

The Innate Immune System Uses Pattern Recognitino Receptors

Infection Triggers Inflammation

Lymphocytes Possess Antigen Receptors

B Lymphocytes Produce Immunoglobulins

Antiboidies Consist of Two Light Chains and Two Heavy Chains

Different Immunoglobulin Classes Have Different Properties

Adaptive Immune Responses Are Based on Clonal Selection

Immunoglobulin genes Are Rearranged During B-Cell Development

The T-Cell Receptor Recruits Cytosolic Tyrosine Protein Kinases

Mediatros of Inflammation Are Produced form Arachidonic Acid

Prostaglandins Are Synthesized in All Tissues

Prostanoids Participate in Many Physiological Processes

Leukotrienes Are Produced by the Lipoxygenase Pathway

Anti-Inflammatory Drugs Inhibit the Synthesis of Eicosanoids

Summary

Chapter 19

CELLULAR GROWTH CONTROL AND CANCER

The Cell Cycle Is Controlled at Two Checkpoints

Cells Can Be Grown in Culture

Cyclins Play Key Roles in Cell Cycle Control

Retinoblastoma Protein Guards the G1 Checkpoint

Cell Proliferation Is Triggered by Mitogens

Mitogens Regulate Gene Expression

Cells Can Commit Suicide

Cancers Are Monoclonal in Origin

Cancer Is Caused by Activation of Growth-Promoting Genes

and Inactivation of Growth-Inhibiting Genes

Some Retroviruses Contain an Oncogene

Retroviruses Can Cause Cancer by Inserting Themselves Next

to a Cellular Proto-Oncogene

Many Oncogenes Code for Components of Mitogenic Signaling

Cascades

Cancer Susceptibility Syndromes Are Caused by Inherited

Mutations in Tumor Suppressor Genes

Many Tumor Suppressor Genes Are Known

Components of the Cell Cycle Machinery Are Abnormal in Most

Cancers

DNA Damage Causes Either Growth Arrest or Apoptosis

Most Spontaneous Cancers Are Defective in p53 Action

The P13K/Protein Kinase B Pathway Is Activated in Many

Cancers

The Products of Some Viral Oncogenes Neutralize the Products

of Cellular Tumor Suppressor Genes

Tumors Become More Malignant through Darwinian Selection

Intestinal Polyps Are Benign Lesions

Intestinal Polyps Can Evolve into Colon Cancer

Summary

Part FIVE

METABOLISM

Chapter 20

DIGESTIVE ENZYMES

Saliva Contains α-Amylase and Lysozyme

Protein and Fat Digestion Start in the Stomach

The Pancreas Is a Factory for Digestive Enzymes

Fat Digestion Requires Bile Salts

Some Digestive Enzymes Are Anchored to the Surface of the

Microvilli

Poorly Digestible Nutrients Cause Flatulence

Many Digestive Enzymes Are Released as Inactive

Precursors

Summary

Chapter 21

INTRODUCTION TO METABOLIC PATHWAYS

Alternative Substrates Can Be Oxidized in the Body Metabolic Processes Are Compartmentalized

Free Energy Changes in Metabolic Pathways Are

Additive

Most Metabolic Pathways Are Regulated

Feedback Inhibition and Feedforward Stimulation Are the Most

Important Regulatory Principles

Metabolism Is Regulated to Ensure Homeostasis

Inherited Enzyme Deficiencies Cause Metabolic Diseases

Vitamin Deficiencies, Toxins, and Endocrine Disorders Can Disrupt

Metabolic Pathways

Summary

Chapter 22

GLYCOLYSIS, TRICARBOXYLIC ACID CYCLE, AND

OXIDATIVE PHOSPHORYLATION

Glucose Uptake into the Cells Is Regulated

Glucose Degradation Begins in the Cytoplasm and Ends in the

Mitochondria

Glycolysis Begins with ATP-Dependent Phosphorylations

Most Glycolytic Intermediates Have Three Carbons

Phosphofructokinase Is the Most Important Regulated Enzyme

of Glycolysis

Lactate Is Produced under Anaerobic Conditions

Pyruvate Is Decarboxylated to Acetyl-CoA in the

Mitochondria

The TCA Cycle Produces Two Molecules of Carbon Dioxide for

Each Acetyl Residue

Reduced Coenzymes Are the Most Important Products of the TCA

Cycle

Oxidative Pathways Are Regulated by Energy Charge and

[NADH]/[NAD+] Ratio

TCA Cycle Provides an Important Pool of Metabolic

Intermediates

Antiporters Transport Metabolites across the Inner Mitochondrial

Membrane

The Respiratory Chain Channels Electrons fromNADH

and FADH2 to Molecular Oxygen

Standard Reduction Potential Is the Tendency to Donate

Electrons

The Respiratory Chain Contains Flavoproteins, Iron-Sulfur

Proteins, Cytochromes, Ubiquinone, and Protein-Bound

Copper

The Respiratory Chain Contains Large Multiprotein

Complexes

The Respiratory Chain Creates a Proton Gradient

The Proton Gradient Drives ATP Synthesis

The Efficiency of Glucose Oxidation Is Close to 40%

Oxidative Phosphorylation Is Limited by the Supply of

ADP

Brown Adipose Tissue Contains an Uncoupling Protein

Mutations in Mitochondrial DNA Can Cause Disease

Summary

Chapter 23

Oxygen Deficiency and Oxygen Toxicity

Ischemia Leads to Infarction

Oxidative Phosphorylation Is Inhbited by Many Poisons

Hypoxia Inducible Factor Adjusts Cell Metabolism to Hypoxia

Reactive Oxygen Derivatives Are Formed during Oxidative Metabolism

The Respiratory Chain Is a Major Source of Superoxide

Cells Have Specialized Enzymes to Destroy Reactive Oxygen Species

Free Radical Formation Is Affected by Energy Supply and Energy Consumption

Some Vitamins and Phytochemicals Can Scavange Free Radicals

The NRF2 Transcription Factor Coordinates Defenses against Reactive Oxygen Species

Phagocytic Cells Use Reactive Oxygen Species for Intracellular Killing

Summary

Chapter 24

CARBOHYDRATE METABOLISM

An Adequate Blood Glucose Level Must Be Maintained at All

Times

Gluconeogenesis Bypasses the Three Irreversible Reactions of

Glycolysis

Fatty Acids Cannot Be Converted into Glucose

Glycolysis and Gluconeogenesis Are Regulated by Hormones

Glycolysis and Gluconeogenesis Are Fine Tuned by Allosteric

Effectors and Hormone-Induced Enzyme

Phosphorylations

Fructose-2,6-biphosphate Switches the Liver from Gluconeogenesis to Glycolysis

Glucokinase Is Regulated by Two Regulatory Proteins

Carbohydrate Is Stored as Glycogen

Glycogen Is 0Synthesized from Glucose

Glycogen Is Degraded by Phosphorolytic Cleavage

Glycogen Metabolism Is Regulated by Hormones and

Metabolites

Glycogen Accumulates in Several Enzyme Deficiencies

Fructose Is Channeled into Glycolysis/Gluconeogenesis

Excess Fructose Is Problematic

Excess Galactose Is Channeled into the Pathways of Glucose

Metabolism

The Pentose Phosphate Pathway Supplies NADPH and

Ribose-5-Phosphate

Fructose Is the Principal Sugar in Seminal Fluid

Amino Sugars and Sugar Acids Are Made from Glucose

Summary

Chapter 25

THE METABOLISM OF FATTY ACIDS AND

TRIGLYCERIDES

Fatty Acids Differ in Their Chain Length and Number of

Double Bonds

Chylomicrons Transport Triglycerides from the Intestine to Other

Tissues

Adipose Tissue Is Specialized for the Storage of Triglycerides

Fat Metabolism in Adipose Tissue Is under Hormonal

Control

Fatty Acids Are Transported into the Mitochondrion

β-Oxidation Produces Acetyl-CoA, NADH, and FADH2

Special Fatty Acids Require Special Reactions

The Liver Converts Excess Fatty Acids to Ketone Bodies

Fatty Acids Are Synthesized from Acetyl-CoA

Acetyl-CoA Is Shuttled into the Cytoplasm as Citrate

Fatty Acid Synthesis Is Regulated by Hormones and

Metabolites

AMP-Activated Protein Kinase Adapts Metabolic Pathways to Cellular Energy Status

Most Fatty Acids Can Be Synthesized from Palmitate

Fatty Acids Regulate Gene Expression

Polyunsaturated Fatty Acids Can Be Oxidized

Nonenzymatically

Summary

Chapter 26

THE METABOLISM OF MEMBRANE LIPIDS 000Phosphatidic Acid Is an Intermediate in Phosphoglyceride

Synthesis

Phosphoglycerides Are Remodeled Continuously

Sphingolipids Are Synthesized from Ceramide

Deficiencies of Sphingolipid-Degrading Enzymes Cause Lipid

Storage Diseases

Cholesterol Is the Least Soluble Membrane Lipid

Cholesterol Is Derived from Both Endogenous Synthesis and the

Diet

Cholesterol Biosynthesis Is Regulated at the Level of HMG-CoA

Reductase

Bile Acids Are Synthesized from Cholesterol

Bile Acids Are Subject to Extensive Enterohepatic Circulation

Most Gallstones Consist of Cholesterol

Summary

Chapter 27

LIPID TRANSPORT

Most Plasma Lipids Are Components of Lipoproteins

Lipoproteins Have Characteristic Lipid and Protein

Compositions

Dietary Lipids Are Transported by Chylomicrons

VLDL Is a Precursor of LDL

LDL Is Removed by Receptor-Mediated Endocytosis

Cholesterol Regulates Its Own Metabolism

HDL Is Needed for Reverse Cholesterol Transport

Lipoproteins Can Initiate Atherosclerosis

Lipoproteins Respond to Diet and Lifestyle

Hyperlipoproteinemias Are Grouped into Five Phenotypes

Hyperlipidemias Are Treated with Diet and Drugs

Summary

Chapter 26

AMINO ACID METABOLISM

Amino Acids Can Be Used for Gluconeogenesis and

Ketogenesis

The Nitrogen Balance Indicates the Net Rate of Protein

Synthesis

The Amino Group of Amino Acids Is Released as Ammonia

Ammonia Is Detoxified to Urea

Urea Is Synthesized in the Urea Cycle

Hyperammonemia Can Be Treated with Diet and Drugs

Some Amino Acids Are Closely Related to Common Metabolic

Intermediates

Glycine, Serine, and Threonine Are Glucogenic

Proline, Arginine, Ornithine, and Histidine Are Degraded to

Glutamate

Methionine and Cysteine Are Metabolically Related

Valine, Leucine, and Isoleucine Are Degraded by Transamination

and Oxidative Decarboxylation

Phenylalanine and Tyrosine Are Both Glucogenic and

Ketogenic

Melanin Is Shesized from Tyrosine

Lysine and Tryptophan Have Lengthy Catabolic Pathways

The Liver Is the Most Important Organ of Amino Acid

Metabolism

Glutamine Participates in Renal Acid-Base Regulation

Summary

Chapter 29

METABOLISM OF IRON AND HEME

Iron Is Conserved Very Efficiently in the Body

Iron Uptake by Cells Is Regulated

Dietary Iron Is Absorbed in the Duodenum

Dietary Iron Absorption Is Regulated

Iron Deficiency Is the Most Common Micronutrient Deficiency Worldwide

Bone Marrow and Liver Are the Most Important Sites of Heme

Synthesis

Heme Is Synthesized from Succinyl-Coenzyme A and Glycine

Porphyrias Are Caused by Deficiencies of Heme-Synthesizing

Enzymes

Heme Is Degraded to Bilirubin

Bilirubin Is Conjugated and Excreted by the Liver

Elevations of Serum Bilirubin Cause Jaundice

Many Diseases Can Cause Jaundice

Summary

Chapter 30

THE METABOLISM OF PURINES AND

PYRIMIDINES

Purine Synthesis Starts with Ribose-5-Phosphate

Purines Are Degraded to Uric Acid

Free Purine Bases Can Be Salvaged

Pyrimidines Are Synthesized from Carbamoyl Phosphate and

Aspartate

DNA Synthesis Requires Deoxyribonucleotides

Many Antineoplastic Drugs Inhibit Nucleotide Metabolism

Uric Acid Has Limited Water Solubility

Hyperuricemia Causes Gout

Abnormalities of Purine-Metabolizing Enzymes Can Cause

Gout

Gout Can Be Treated with Drugs

Summary

Chapter 31

MICRONUTRIENTS

Riboflavin Is a Precursor of Flavin Mononucleotide

and Flavin Adenine Dinucleotide

Niacin Is a Precursor of NAD and NADP

Thiamin Deficiency Causes Weakness and Amnesia

Vitamin B6 Plays a Key Role in Amino Acid Metabolism

Pantothenic Acid Is a Building Block of Coenzyme A

Biotin Is a Coenzyme in Carboxylation Reactions

Folic Acid Deficiency Causes Megaloblastic Anemia

Vitamin B12 Requires Intrinsic Factor for Its Absorption

Vitamin C Is a Water-Soluble Antioxidant

Retinol, Retinal, and Retinoic Acid Are the Active Forms of

Vitamin A

Vitamin D Is a Prohormone

Vitamin E Prevents Lipid Oxidation

Many Vitamins and Phytochemicals Are Antioxidants

Vitamin K Is Required for Blood Clotting

Zinc Is a Constituent of Many Enzymes

Copper Participates in Reactions of Molecular Oxygen

Some Trace Elements Serve Very Specific Functions

Summary

Chapter 32

INTEGRATION OF METABOLISM

Insulin Is Released in Response to Elevated Glucose

Insulin Stimulates the Utilization of Nutrients

Protein Synthesis Is Coordinated by the mTOR Complex

Glucagon Maintains the Blood Glucose Level

Catecholamines Mediate the Flight-or-Fight Response

Glucocorticoids Are Released in Chronic Stress

Energy Is Expended Continuously

Stored Fat and Glycogen Are Degraded between Meals

Adipose Tissue Is the Most Important Energy Depot

The Liver Converts Dietary Carbohydrates to Glycogen

and Fat after a Meal

The Liver Maintains the Blood Glucose Level during Fasting

Ketone Bodies Provide Lipid-Based Energy during

Fasting

Obesity Is Common

in All Affluent Countries

Appetite Control Is the Most Important Determinant of Obesity

Obesity Is Related to Insulin Resistance

Diabetes Is Caused by Insulin Deficiency or Insulin

Resistance

In Diabetes, Metabolism Is Regulated as in

Starvation

Diabetes Is Diagnosed with Laboratory Tests

Diabetes Leads to Late Complications

Many Drugs Are Available for Diabetes Treatment

Contracting Muscle Has Three Energy Sources

Catecholamines Coordinate Metabolism during Exercise

Physical Exercise Leads to Adaptive Changes

Ethanol Is Metabolized to Acetyl-CoA in the Liver

Liver Metabolism Is Deranged by Alcohol

Alcoholism Leads to Fatty Liver and Liver Cirrhosis

Most "Diseases of Civilization" Are Caused by Aberrant

Livestyles

Aging Is the Greatest Challenge for Medical Research

Anti-Aging Treatments Are Being Investigated

Summary

ANSWERS TO QUESTIONS

GLOSSARY

CREDITS

EXTRA ONLINE-ONLY CASE STUDIES {more new Cases to be added, to come}

The Mafia Boss

Viral Gastroenteritis

Death in Installments

A Mysterious Death

To Treat or Not to Treat?

Yellow Eyes

An Abdominal Emergency

Shortness of Breath

Itching

Abdominal Pain

Rheumatism

A Bank Manager in Trouble

Kidney Problems

Gender Blender

Man Overboard!

Spongy Bones

Blisters

The Sunburned Child

Too Much Ammonia

ANSWERS TO CASE STUDIES

Details

No. of pages:
657
Language:
English
Copyright:
© Elsevier 2017
Published:
Imprint:
Elsevier
eBook ISBN:
9780323391917
eBook ISBN:
9780323391863
eBook ISBN:
9780323391900
eBook ISBN:
9780323391870
eBook ISBN:
9780323391894
Paperback ISBN:
9780323296168

About the Author

Gerhard Meisenberg

Affiliations and Expertise

Course Director Medical Biochemistry, Ross University, Dominica, West Indies

William Simmons

Affiliations and Expertise

Department of Molecular Pharmacology and Therapeutics, Loyola University School of Medicine, Maywood, Illinois