Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin. The crystal structure of human HO-1 in complex with heme reveals a novel helical structure with conserved glycines in the distal helix, providing flexibility to accommodate substrate binding and product release (Schuller, D. J., Wilks, A., Ortiz de Montellano, P. R., and Poulos, T. L. (1999) Nat. Struct. Biol. 6, 860-867). To ...

5-Aminolevulinic acid (ALA) is the rate-limiting intermediate in heme biosynthesis vertebrate species; a reaction catalyzed by mitochondrial ALA synthase 1 (ALAS1) enzyme. Previously we reported that knockdown of ubiquitously expressed ALAS1 gene mice disrupts normal glucose metabolism, attenuates function and results prediabetic like phenotype when animals pass 20-weeks age (Saitoh et al., 201...

In this issue of Blood, Kovtunovych et al report the curative effect of a nonmyeloablative bone marrow transplant for anemia and organ dysfunction in heme oxygenase 1 (HO-1)-deficient mice by restoring the ability to detoxify heme through the repopulation of the tissues with wild-type macrophages. These findings provide the basis for new therapies for this lethal disorder in children lacking th...

Blue egg coloring is attributed to biliverdin derived from the oxidative degradation of heme through catalysis by heme oxygenase (HO). The pigment is secreted into the eggshell by the shell gland. There is uncertainty as to whether the pigment is synthesized in the shell gland or in other tissues. To investigate the site of pigment biosynthesis, the expression of heme oxygenase (decycling) 1 (H...

The bilin prosthetic groups of the phytochrome photoreceptors and the light-harvesting phycobiliprotein antennae arise from the oxygen-dependent ring opening of heme. Two ferredoxin-dependent enzymes contribute to this conversion: a heme oxygenase and a bilin reductase with discrete double-bond specificity. Using a dual plasmid system, one expressing a truncated cyanobacterial apophytochrome 1,...

background: heme oxygenase-1 (ho-1) is a cytoprotective and antiapoptotic enzyme, which has been involved in maintaining cellular homeostasis, and plays an important protective role by modulating oxidative injury. up-regulation of (ho-1) has contributed to tumorogenicity of some cancers. in this study we investigated the expression pattern of the ho-1, in five different human-derived cancer cel...

The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophob...

The response regulator HrrA of the HrrSA two-component system (previously named CgtSR11) was recently found to be repressed by the global iron-dependent regulator DtxR in Corynebacterium glutamicum. Here, we provide evidence that HrrA mediates heme-dependent gene regulation in this nonpathogenic soil bacterium. Growth experiments and DNA microarray analysis revealed that C. glutamicum is able t...

Treatment of rats in vivo with cobalt chloride stimulated heme oxidation by hepatic microsomes to levels up to 800% above controls. This treatment also caused increases in liver weight and in total microsomal protein; in contrast, marked decreases were produced in microsomal oxidation of ethylmorphine (80%), and in cytochrome P-450 (60-70%) and heme (30-50%) contents. Cobalt chloride treatment ...

We examined the effects of heme administration (15 mg/kg IV) on indexes of renal carbon monoxide production and contrasted the renal functional response to heme in anesthetized rats pretreated and not pretreated with stannous mesoporphyrin (40 micromol/kg IV) to inhibit heme oxygenase or sodium meclofenamate (5 mg/kg IV plus infusion at 10 microg/kg per minute) to inhibit cyclooxygenase. In rat...