Carbon monoxide production from hydroxocobalamin by bacteria

Engel, Rolf R.; Modler, Siv; Matsen, John M.; Petryka, Z.J.

doi:10.1016/0304-4165(73)90195-5

Cited by 36 publications

(24 citation statements)

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“…Because undegraded heme is excreted into the intestine with the bile (12,13), two explanations were offered for the observed phenomenon. 1) The antibiotics had eradicated the heme-degrading, CO-producing bacteria ( 14) in the gut or 2) the antibiotics had directly inhibited intestinal HO. The present study, however, eliminates the possibility of T P treatment in animals that had prophylactically received broad-spectrum antibiotics did not exclude some measurable contribution to the VeCO by intestinal H O degradation of heme, reaching the intestine via the bile (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…Preliminary studies in our laboratory suggested that a single dose of TP has no suppressive effect on the excretion rate of CO (VeCO) in suckling rats (9, 10) unless the animals are first treated with broad spectrum antibiotics (1 I). Later studies, showing that heme is excreted into the bile of TPtreated adult rats (12,13) pointed to two possible explanations for the paradox: 1) heme-degrading bacteria in the intestine produced CO (14), thus preventing us from observing the inhibitory effects of TP until the bacteria were eradicated by antibiotics or 2) antibiotics directly inhibited intestinal HO. Because heme reaching the intestine can be catabolized to bilirubin and CO by intestinal tissue HO (1 5), the question of inhibition of intestinal HO has potential clinical importance.…”

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confidence: 99%

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Lack of Inhibition of Intestinal Heme Oxygenase by Antibiotics and Tin-Protoporphyrin

et al. 1988

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A B S T R A a . W e assessed the in vivo and in vitro effects of antibiotics and tin-protoporphyrin (TP) on intestinal heme oxygenase (HO) activity using a gas chromatographic assay. This method measures the carbon monoxide produced from heme in the presence of NADPH. After in vivo administration of kanamycin (10 mg/kg body weight), ampicillin (200 mg/kg body weight) or neomycin (60 mg/ kg body weight) with or without T P (65 pmol/kg body weight) to suckling rats, no significant difference in HO activity along the small intestine was observed. I n vitro exposure of adult rat intestinal preparations to the antibiotics showed no significant decrease in H O activity between control and experimental tissue preparations. A concentration-dependent stimulatory effect of neomycin was observed. Subcutaneous administration of T P (25 pmol/kg body weight) to adult male Wistar rats revealed no significant inhibition of the intestine. However, in vitro addition of T P (12.5 pM) to the control tissue preparations of adult Wistar rats revealed highly significant inhibition in liver and spleen when compared to the unexposed control tissues. In contrast, when T P was added to control intestinal preparations no inhibition was observed. These findings suggest that suckling rat intestinal heme oxygenase is not inhibited by in vivo treatment with high concentrations of kanamycin, ampicillin, or neomycin. Furthermore, these antibiotics are not in vitro inhibitors of adult rat intestinal HO. Finally, adult rat intestinal H O is not inhibited either in vivo or in vitro by a concentration of TP that significantly inhibits liver and spleen activity. (Pediatr Res 23: 50-53, 1988) Abbreviations CO, carbon monoxide TP, tin-protoporphyrin HO, heme oxygenase VeCO, excretion rate of C O TP, a synthetic heme analog, has been reported to be a competitive inhibitor of HO (1-3). This rate-limiting enzyme in the heme catabolic pathway (4) catalyzes the equimolar formation of bilirubin and CO. In vivo studies with TP have demonstrated the drug's effectiveness in lowering serum bilirubin levels in rats ( 3 , in mice with severe hemolytic anemia (6) in rhesus monkeys (7), and in man (8). Preliminary studies in our laboratory suggested that a single dose of TP has no suppressive effect on the excretion rate of CO (VeCO) in suckling rats (9, 10) unless

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Section: Discussionmentioning

confidence: 99%

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Lack of Inhibition of Intestinal Heme Oxygenase by Antibiotics and Tin-Protoporphyrin

et al. 1988

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“…The process of heme degradation has been well studied in eukaryotes, in which a family of enzymes-heme oxygenasescatalyze oxidative cleavage of heme to biliverdin (16,31). Detection of carbon monoxide, a product of the heme oxygenase reaction, in gram-positive organisms such as Bacillus cereus and Streptomyces mitis, suggested the existence of heme oxygenase activity (8). A heme oxygenase (HmuO), essential for utilization of heme and Hb-iron, was recently identified and characterized from the gram-positive pathogen Corynebacterium diphtheriae (22,34).…”

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Degradation of Heme in Gram-Negative Bacteria: the Product of the hemO Gene of Neisseriae Is a Heme Oxygenase

2000

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A full-length heme oxygenase gene from the gram-negative pathogen Neisseria meningitidis was cloned and expressed in Escherichia coli. Expression of the enzyme yielded soluble catalytically active protein and caused accumulation of biliverdin within the E. coli cells. The purified HemO forms a 1:1 complex with heme and has a heme protein spectrum similar to that previously reported for the purified heme oxygenase (HmuO) from the gram-positive pathogen Corynebacterium diphtheriae and for eukaryotic heme oxygenases. The overall sequence identity between HemO and these heme oxygenases is, however, low. In the presence of ascorbate or the human NADPH cytochrome P450 reductase system, the heme-HemO complex is converted to ferric-biliverdin IX␣ and carbon monoxide as the final products. Homologs of the hemO gene were identified and characterized in six commensal Neisseria isolates, Neisseria lactamica, Neisseria subflava, Neisseria flava, Neisseria polysacchareae, Neisseria kochii, and Neisseria cinerea. All HemO orthologs shared between 95 and 98% identity in amino acid sequences with functionally important residues being completely conserved. This is the first heme oxygenase identified in a gram-negative pathogen. The identification of HemO as a heme oxygenase provides further evidence that oxidative cleavage of the heme is the mechanism by which some bacteria acquire iron for further use.

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“…Therefore, externally supplied heme can not satisfy cells' requirements for iron without the involvement of heme degradation. Early studies that measured production of carbon monoxide, a byproduct of heme degradation, in the grampositive organisms Bacillus cereus and Streptococcus mitis suggested the existence of a heme oxygenase-like activity in bacteria (9). In addition to their role in iron assimilation, heme oxygenases might protect cells against heme toxicity (3).…”

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Use of Heme Compounds as Iron Sources by Pathogenic Neisseriae Requires the Product of the hemO Gene

et al. 2000

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Heme compounds are an important source of iron for neisseriae. We have identified a neisserial gene, hemO, that is essential for heme, hemoglobin (Hb), and haptoglobin-Hb utilization. The hemO gene is located 178 bp upstream of the hmbR Hb receptor gene in Neisseria meningitidis isolates. The product of the hemO gene is homologous to enzymes that degrade heme; 21% of its amino acid residues are identical, and 44% are similar, to those of the human heme oxygenase-1. DNA sequences homologous to hemO were ubiquitous in commensal and pathogenic neisseriae. HemO genetic knockout strains of Neisseria gonorrhoeae and N. meningitidis were unable to use any heme source, while the assimilation of transferrin-iron and iron-citrate complexes was

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Carbon monoxide production from hydroxocobalamin by bacteria

Cited by 36 publications

References 13 publications

Lack of Inhibition of Intestinal Heme Oxygenase by Antibiotics and Tin-Protoporphyrin

Lack of Inhibition of Intestinal Heme Oxygenase by Antibiotics and Tin-Protoporphyrin

Degradation of Heme in Gram-Negative Bacteria: the Product of the hemO Gene of Neisseriae Is a Heme Oxygenase

Use of Heme Compounds as Iron Sources by Pathogenic Neisseriae Requires the Product of the hemO Gene

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