Heme Biology: The Secret Life of Heme in Regulating Diverse Biological Processes

CONTENTS......Page 10
Preface......Page 8
List of Contributors......Page 12
Overview......Page 14
References......Page 19
Heme is synthesized by the actions of eight enzymes in humans......Page 20
Heme biosynthesis is regulated according to the needs for heme in human cells......Page 23
Defective heme biosynthesis causes serious diseases in humans......Page 25
Heme is degraded continuously in the human body......Page 31
Defects in heme degradation can cause serious diseases......Page 33
References......Page 35
Heme can control the activity of diverse transcriptional regulators......Page 46
Heme serves as a secondary messenger of oxygen in yeast......Page 47
Heme can control the expression of a high number of genes in yeast......Page 48
The heme activator protein Hap1 is a key regulator of gene transcription in response to fluctuations in oxygen and heme levels......Page 50
Heme regulation of Hap1 transcription-activating activity requires the proper functioning of Hsp90 and Hsp70 molecular chaperones......Page 54
Bach1: A heme-dependent transcriptional regulator in mammalian cells......Page 56
Bach1, like Hap1, binds to heme via HRMs......Page 57
Heme affects Bach1 at three levels......Page 58
References......Page 60
Overview......Page 68
HRI is responsible for heme-regulated translation in erythroid precursors......Page 69
Phosphorylation of eIF2α under diverse cellular stresses by the family of eIF2α kinases......Page 71
Activation of HRI by autophosphorylation......Page 73
Two distinct heme-binding domains in the cooperation of heme-regulation of HRI......Page 75
Tissue expression and phylogenetic conservation of HRI......Page 78
Coordination of heme and globin synthesis by HRI......Page 79
Regulation of erythroid differentiation by HRI......Page 82
Integrated stress response of eIF2αP signaling......Page 84
Concluding remarks......Page 86
References......Page 87
Overview......Page 98
Heme synthesis and disturbances pertinent to neuronal cells......Page 99
Contradictory roles of heme as a toxic and a physiological molecule......Page 102
Acute damage......Page 104
Neuroglobin, hemoglobin and their neuroprotective roles......Page 106
Heme oxygenases and neurodegenerative diseases: Where does heme come from?......Page 108
Emerging regulatory roles for heme in neurons......Page 112
Neurotrophic effects of heme......Page 117
Heme and brain aging: Role of heme for protection from drug-induced neurotoxicity......Page 121
May sufficient availability of heme delay aging?......Page 123
Deficiency of heme and Alzheimer’s disease......Page 124
Heme in circadian pathways......Page 127
References......Page 128
miRNAs and the miRNA biogenesis pathway......Page 140
DiGeorge Critical Region 8......Page 142
DGCR8 binds heme......Page 143
Redox regulation of pri-miRNA processing activity of heme-bound DGCR8 by glutathione......Page 144
A novel use of WW motif for dimerization and for association with heme......Page 145
The C-terminal region of the HBD is an autoinhibitory domain......Page 147
Future directions......Page 148
References......Page 149
Molecular and cellular events underlie proper human functioning......Page 152
Heme controls the growth, differentiation, and death of diverse cells......Page 153
Heme has the potential to modulate the activities of many regulatory proteins that are crucial for proper human functioning......Page 155
Experimental evidence shows that heme can indeed bind to and regulate the activity of protein tyrosine kinases......Page 158
References......Page 164
Overview......Page 174
Introduction......Page 175
Heme protein architectures......Page 177
Heme exposure and solvent accessibility......Page 178
Ligation of the heme iron......Page 179
Covalent linkage......Page 182
Hydrophobic and electrostatic interactions......Page 184
Reversible heme-binding protein......Page 185
Structure and reduction potentials......Page 188
Heme-mediated signal transduction......Page 190
References......Page 194
Biosynthesis of PpIX......Page 210
Mechanism of PDT......Page 212
Levulan® (5-ALA, 5-Aminolevulinic acid hydrochloride)......Page 214
Visudyne® (Verteporfin, benzoporhyrin derivative, BPD-MA)......Page 217
Foscan® (temoporfin, meta-tetrahydroxyphenylchlorin, or m-THPC)......Page 218
Acknowledgement......Page 219
References......Page 220
Index......Page 224