Heme oxygenase 1

Heme oxygenase is a microsomal enzyme that catalyzes the first and ratedetermining step in the degradation of heme. This assay measures bilirubin, 

This assay is based on the separation and quantitation of bilirubin. The column was a C18 Novapak radial compression column. Solvent A contained 49% 0.1 M monobasic ammonium phosphate, 40% methanol, 10% acetonitrile, and 1% DMSO, adjusted with H3PO4 to pH 3.6. Solvent B contained 79% methanol, 20% acetonitrile, and 1% DMSO. The 16-minute run included a linear gradient from 50 to 100% solvent B in 3 minutes, maintaining 100% B for 13 minutes, followed by a return to starting conditions. The eluate was monitored at 450 nm, and detector response was linear with 0 to 500 pmol of bilirubin. 

The 1 mL reaction mixture contained heme oxygenase, 5 mM deferroxa-mine, 25 piM hemin, 15 fiM bovine serum albumin, 1 mM NADPH, 0.1 M potassium phosphate (pH 7.4), and 0.05 mL of 105,000g supernate from 20% (w/v) perfused rat liver homogenate as a source of biliverdin reductase. To stop the reaction, 0.1 mL of the reaction mixture was added to 0.1 mL of ethanol-DMSO (95 5, v/v). After 2 minutes incubation on ice, the mixture was centrifuged and 0.1 mL of the supernate was injected on HPLC. The rate of bilirubin formation was linear up to 0.63 mg protein/0.237 mL assay, and up to 9 minutes incubation at 37°C. 

The enzyme preparations assayed were the 10,000g (10 min) supernate fractions from livers of chick embryos and rats, and liver biopsy samples from humans. 

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All mammalian cells are virtually capable of producing CO with heme as the main substrate (Fig. 1) [5]. Enzymatic heme metabolism in vivo is mainly catalyzed by heme oxygenase (HO). In the presence of HO, the porphyrin ring of heme is broken and oxidized at the a-methene bridge, producing equimolar amounts of CO, ferrous iron, and biliverdin. Three isoforms of HO have been identified. Inducible HO-1 (32 kDa) is mostly recognized for its upregulation in response... 

Carbon Monoxide. Figure 1 Heme oxygenase catalyzed heme metabolism (from Pharmacol Rev 57 585-630,... 

Hyjjerbilirubinaemia is an abnormality observed mainly in neonates in whom the liver is insufficiently developed to be able to detoxify the bile pigment bilirubin. This situation is known as neonatal jaundice and can sometimes become a serious disease causing neurotoxic symptoms. Bilirubin is produced by the degradation of heme [the Fe(II) complex of protoporphyrin IX] by heme oxygenase to give biliverdin, which is reduced by biliverdin reductase to... 

Narayan S, Misra UK. 1985. Delta-aminolevulinic acid synthetase and heme oxygenase activity in lung and liver of rats given DDT and endosulfan intratracheally. Bull Environ Contam Toxicol 34 24-28. 

Figure 32-12. Schematic representation of the microsomal heme oxygenase system. (Modified from Schmid R, McDonough AF in The Porphyrins. Dolphin D [editor]. Academic Press, 1978.)...

Catabohsm of the heme ring is initiated by the enzyme heme oxygenase, producing a hnear tetrapyr-role. 

Jeong, G.S. et al.. Comparative effects of curcuminoids on endothelial heme oxygeanse-1 expression ortho-methoxy groups are essential to enhance heme oxygenase activity and protection, Exp. Molec. Med., 38, 393, 2006. 

Matsui T, M Furukawa, M Unno, T Tomita, M Ikeda-Saito (2005) Roles of distal Asp in heme oxygenase from Corynebacterium diphtheriae, HmuO. A water-driven oxygen activation system. J Biol Chem 280 2981-2989. 

Suits MDL, GP Pal, K Nakatsu, A Matte, M Cygler, Z Jia (2005) Identification of an Escherichia coli 0157 H7 heme oxygenase with tandem functional repeats. Proc Natl Acad USA 102 16955-16960. 

Wegele R, R Tasler, Y Zeng, M Riveras, N Frankenberg-Dinkel (2004) The heme oxygenase(s)-phytochrome sysyem of Pseudomonas aeruginosa. J Biol Chem 279 45791-45802. 

Wilks A, MP Schmitt (1998) Expression and characterization of a heme oxygenase (Hmu O) from Corynebacterium diphtheriae. J Biol Chem 2iy. 837-841. 

Zhu W, A Wilks, I Stojiljkovic (2000) Degradation of heme in Gram-negative bacteria the product of the hemO gene of Neisseriae is a heme oxygenase. J Bacterial 182 6783-6790. 

S-Adenosylmethionine carboxylase Sex-hormone binding globulin CYP 2D6 Falcipain 2 and 3 SARS CoV Chkl kinase Heme oxygenase... 

Some of the above mentioned studies also use two-layer ONIOM QM MM approaches to include the full protein in an MM description. Other examples of QM MM calculations of metal enzymes include heme oxygenase [89], nitrate reductase [90] and peptide deformylase [91]. Finally, we note that the ONIOM (I IF Amber) potential energy surface has been directly used in a molecular dynamics study (ONIOM/MD) of cytidine deaminase [92],... 

Grosser N et al (2004) The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Radic Biol Med 37(12) 2064-2071... 

Obermuller-Jevic, UC. Schlegel, B. Flaccus, A., and Biesalski, HK. 2001. The effect of beta-carotene on the expression of interleukin-6 and heme oxygenase-1 in UV-irradiated human skin fibroblasts in vitro. FEBS Lett 509 186-190. 

Improving functionality may involve a complex biocatalytic system including more than one biocatalyst, as it is the case in BDM reactions. Additionally to the BDS for instance, another biocatalyst active for BDM [395,406], which consists of a heme oxygenase or a Cytochrome reductase could be used to widen up the functionality. 

Saikawa Y, Kaneda H, Yue L et al. Structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in a human case with heme oxygenase-1 deficiency. Hum Mutat 2000 16[2] 178—179. 

Enzymes Nitric Oxide Synthase and Heme Oxygenase... 

Heme Oxygenase Structure and Mechanism Paul R. Ortiz de MonteBano and Angela Wilks... 

Sunderman, F.W., Jr., M.C. Reid, L.M. Bibeau, and J.V. Linden. 1983. Nickel induction of microsomal heme oxygenase activity in rodents. Toxicol. Appl. Pharmacol. 68 87-95. 

Enzymes Nitric Oxide Synthase and Heme Oxygenase Thomas L. Poulos, Huiying Li,... 

Several other metal complexes have promising photodynamic activity and are currently under development (248). Metalloporphyrins inhibit the enzyme heme oxygenase for example, chromium porphyrin and mesoporphyrin are potent inhibitors of heme oxygenase both in vitro and in vivo (249, 250) and are being used for the treatment of the neonatal jaundice. 

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