Handbook of Porphyrin Science

The following sections are included:

• Contents

• Preface for Volumes 26–30

• Preface for Volumes 21–25

• Contributing Authors for Volumes 1–30

• Contents of Volumes 1–30

The following sections are included:

• List of Abbreviations

• Introduction

• Two Pathways for Aminolevulinate
  • ALA, the First Common Precursor to All Tetrapyrroles
  • C₄ (Shemin) and C₅ Pathways

• Citric Acid Cycle in Relation to the First Step of Heme Biosynthesis

• 5-Aminolevulinate Synthase
  • ALAS Activity
  • Two ALAS Isoforms
  • Isolation and Purification
  • Cloning, Expression, and Overproduction

• ALAS Gene Structure and Transcriptional Regulation
  • Housekeeping ALAS Gene
  • Erythroid-Specific ALAS Gene
  • Regulation of ALAS1 Expression
  • Regulation of ALAS2 Expression

• Translational Regulation of Erythroid-Specific ALAS mRNA
  • Iron-Responsive Elements
  • IRE-binding Proteins
  • Mechanism of Regulation of ALAS2 Translation

• Protein Stability
  • ALAS1 Stability
  • ALAS2 Stability and Proteasomal Inhibition

• Mitochondrial Import
  • Import Leader Sequence and Mitochondrial Import
  • Heme Inhibition of Mitochondrial Import
  • Heme-regulatory Motifs

• ALAS and PLP-Dependent Enzymes
  • PLP Cofactor and the Schiff Base Linkage to ALAS
  • PLP Cofactor-Dependent Enzymes Superfamily: Classification Based on Structure or Reaction Mechanism
  • α-Oxoamine Synthase Family

• ALAS Structure
  • Oligomeric State and Active Site Arrangement
  • Homology Modeling, and Active Site Architecture
  • Crystal Structures

• ALAS Reaction Mechanism
  • Chemical and Kinetic Mechanisms
  • Protein Conformational Changes and Reaction Rate-limiting Step
  • Roles of Specific Active Site Amino Acids
  • Deprotonation, Protonation, and Decarboxylation Steps
  • Active Site Loop and Reaction Rate-limiting Step

• Erythroid ALAS-Related Disorders
  • X-linked Sideroblastic Anemia
  • X-linked Dominant Erythropoietic Protoporphyria

• Summary and Perspectives for the Future

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• The PBGS-Catalyzed Reaction

• Myriad Metals of PBGS
  • A Non-Essential Zinc Binding Site At/Near the PBGS Active Site
  • The Inhibitory Lead
  • A Third Zinc of Drosophila PBGS
  • The Allosteric Magnesium Ion
  • Monovalent Cations

• The Structure of PBGS and Its Quaternary Structure Equilibrium
  • The PBGS Monomer
  • PBGS Quaternary Structure Dynamics

• Human PBGS and Human Disease

• Moonlighting Functions of PBGS

• Quaternary Structure Dynamics as a Basis for Allosteric Regulation
  • Quaternary Structure Dynamics as a Basis for Regulation of PBGS
  • PBGS Quaternary Structure Dynamics as a Basis for Drug Discovery
  • Beyond PBGS — The Morpheein Model of Allosteric Regulation
  • Using the Behavior of PBGS to Identify Proteins that Might Use the Morpheein Model of Allosteric Regulation
  • Morpheeins as a General Target for Allosteric Drug Discovery

• Summary and Future Directions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Protoporphyrin IX, Ferrous Iron, and Heme

• Requirement for Ferrochelatase
  • Eukaryotic Ferrochelatase
  • Prokaryotic Ferrochelatase

• Ferrochelatase Gene Structure and Transcriptional Regulation
  • Structural Features of the Mammalian Ferrochelatase Gene and Promoter Region
  • Regulation of Expression of the Mammalian Ferrochelatase Gene

• Subcellular Targeting of Ferrochelatase

• Ferrochelatase Structure
  • Common Structural Features between Prokaryotic and Eukaryotic Ferrochelatases
  • Distinct Structural Features between Prokaryotic and Eukaryotic Ferrochelatases

• Synthesis of Protoporphyrin IX and Delivery to Ferrochelatase
  • PPOX-catalyzed Reaction
  • PPOX Active Site and Reaction Mechanism
  • Protoporphyrin IX Transport and Delivery

• Coordination of Porphyrin and Iron Metabolism in Relation to Heme Biosynthesis

• Ferrochelatase-catalyzed Reaction
  • Binding of Protoporphyrin IX and Ferrous Iron to the Active Site of Ferrochelatase
  • Catalytic Mechanism
  • Heme Release

• Ferrochelatase-Related Disorders

• Applications to Medicine
  • Biomarkers
  • Molecular Tumor Imaging and Ferrochelatase Small Interfering RNA

• Summary and Perspectives for the Future

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• HasA-Type Hemophores
  • Mechanisms of Heme Extraction from Hemoproteins
  • Mechanism of Heme Transfer from Hemophore HasA to the Receptor Involved in Transport

• HxuA-Type Hemophores

• The NEAT-Type Hemophores
  • Mechanisms of Heme Extraction from Hemoproteins
  • Mechanism of Heme Transfer between Isd Proteins and IsdE, the Binding Lipoprotein of the Transporter

• Other Types of Hemophores

• Heme Outer Membrane Receptors

• Heme Permeases
  • Heme Permeases in Gram-Negative Bacteria
  • Heme Permeases in Gram-Positive Bacteria

• Heme Efflux Proteins

• Heme-Binding Regulators

• Concluding Remarks

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Heme Biosynthesis
  • Synthesis of 5-Aminolevulinate
  • Synthesis of the Monopyrrole, Porphobilinogen
  • Assembly of the Linear Tetrapyrrole
  • Cyclization of the Tetrapyrrole to Form Uroporphyrinogen
  • Decarboxylation of Uroporphyrinogen
  • Formation of the Vinyl Groups of Protoporphyrinogen IX
  • Oxidation of the Porphyrinogen to Protoporphyrin IX
  • Insertion of Iron to Form Protoheme IX
  • Possible Role of Supramolecular Protein Assemblies in Heme Synthesis

• Regulation of Metazoan Heme Biosynthesis

• Heme Transport and Trafficking
  • Heme Import in Animals
  • Heme Export in Animals
  • Intracellular Heme Transport
  • Contradictions
  • Heme Transfer between Organelles
  • Heme Reductases

• Cytoplasmic Heme-binding Proteins

• Extracellular Heme-binding Proteins

• Intercellular Heme Transport

• Parasitic Worms and Heme

• Heme Transport in Insects

• Heme Transport in Yeast

• Conclusions and Future Directions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• The Quest for Iron: Supply and Demand
  • Overview of Iron Homeostasis
  • Iron Homeostasis and Immunity

• Heme Capture a Critical Mechanism in the Armory of Bacterial Pathogens
  • Navigating the Challenge of the Gram-positive Bacterial Cell Wall
  • Active Heme Transport Across the Gram-negative Bacterial Outer Membrane
  • Periplasmic Heme Trafficking
  • ATP-dependent Transport of Heme Across the Cytoplasmic Membrane
  • Heme Release from the ABC-transporter to the Cytoplasmic Heme-binding Proteins

• Biophysical Properties and Common Motifs of the Heme Transport Proteins
  • Relevance of Heme Coordination and Redox to Heme Transfer
  • Protein–Protein Interaction and Heme Transfers

• Intracellular Heme Utilization and Iron Release
  • Bacterial Heme Oxygenases
  • Iron Release by Non-Heme Oxygenase Mechanisms
  • The Role of Biliverdin in Bacterial Signaling
  • Exogenously Acquired Heme Insertion into Bacterial Proteins

• Regulation of Heme Uptake
  • Transcriptional Regulation of Heme Uptake
  • Post-transcriptional Regulation of Heme and Iron Uptake
  • Extracellular Signaling

• Heme Uptake and Utilization in Antimicrobial Drug Development
  • Outer Membrane Heme-receptors as Vaccine Targets
  • Metalloporphyrin-based Inhibitors of Heme Utilization
  • Small Molecule Inhibitors of Intracellular Heme Utilization

• Conclusions and Future Directions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Role of Heme in Immune Defense
  • Heme as an Immune Modulator
  • Nutritional Immunity: Heme Sequestration in the Host

• Interactions of Infectious Agents with Host Heme
  • Bacterial Pathogens
  • Fungal Pathogens
  • Parasitic Pathogens
  • Prion Diseases
  • Viral Infections

• Impact of Hemoprotein Variations on Infectious Disease
  • Malaria Hypothesis
  • Hemoprotein Polymorphisms and Infectious Disease Susceptibility

• Impact of Heme Synthesis on Infection

• Impact of Heme Catabolism on Infection
  • Heme Catabolism and Viral Infections
  • Heme Catabolism and Bacterial Infections
  • Heme Catabolism and Parasitic Infections

• Heme By-products as Immunomodulators

• Heme-dependent Therapeutic Approaches

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Structure, Regulation, and Cell and Tissue Distribution of Reductase Activity of Heme Degradation Pathway
  • Evolution and Phylogenetic Distribution of BVR
  • Structure
  • Regulation
  • Cell and Tissue Distribution of BVR
  • Mechanism of Reductase Activity

• Signaling Activity of BVR
  • Insulin/IGF-1
  • PI3K/MAPK
  • Intracellular Transport
  • Gene Regulation
  • PKC Interaction
  • Role of hBVR in Activation of ERK1/2 by MEK1/2 and PKCδ

• BVR Expression in Disease States

• Bile Pigments/BVR/HO in Cytoprotection
  • Bilirubin Toxicity
  • Bilverdin and Bilirubin as Antioxidants
  • Bilirubin/Biliverdin Cycling
  • BVR and Biliverdin as Modulators of Immune Function

• Therapeutic Applications of Bile Pigments, BVR, and Its Fragments
  • Bile Pigments
  • Peptides

• Conclusions and Future Directions

• Acknowledgments

• References

The following sections are included:

• List of Abbreviations

• Introduction

• Sources, Subdivisions, and Biochemistry of Superfamily Members
  • C-Family: Dioxygen-Generating Clds
  • C-Family: Proteins from Non-perchlorate Respirers and Members of COG3253S
  • D-Family: Dye-decoloring Peroxidases
  • E-Family: Tat-Transport and Involvement in Fe Metabolism

• Crystal Structures
  • Fold and Domain Structure for the Superfamily
  • Oligomerization within the Superfamily
  • Active Site Differences within the Superfamily
  • Substrate/Product Channels within the Superfamily

• Summary and Perspectives for the Future

• Acknowledgments

• References

The following sections are included:

• Index to Volume 26