Carbon Monoxide Production Associated with Ineffective Erythropoiesis*

White, Peter; Coburn, Ronald F.; Williams, William J.; Goldwein, Manfred I.; Rother, Mary; Shafer, Brenda

doi:10.1172/jci105688

Cited by 52 publications

(30 citation statements)

References 36 publications

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“…The administration of glycine-2-14C to a dog was not followed by the appearance of 14CO in the present study, but the amount of glycine injected was small and the experiment was short. Analogous to our experiments with man (29), a small amount of 14CO probably was formed but could not be detected in rebreathing gas by the ionization chambers. A comment is required regarding the baseline Vco in anesthetized dogs.…”

Section: Introductionsupporting

confidence: 82%

“…It is possible that protoporphyrin served as a precursor of heme, which was then degraded to CO. Others have demonstrated the conversion of hemin and protoporphyrin to bile pigment in animals (26)(27)(28). The present experiments demonstrate that degradation of hemoglobin precursors can give rise to CO, and it is thus possible that the CO and bile pigment that appear shortly after the injection of glycine-2-14C in man (29) may arise from these compounds rather than from hemoglobin. The administration of glycine-2-14C to a dog was not followed by the appearance of 14CO in the present study, but the amount of glycine injected was small and the experiment was short.…”

Section: Introductionmentioning

confidence: 55%

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The Production of Carbon Monoxide from Hemoglobin In Vivo*

Coburn¹,

Williams²,

White³

et al. 1967

J. Clin. Invest.

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Summary. Dogs anesthetized with pentobarbital were shown to produce carbon monoxide at an average rate of 0.21 + (SD) 0.05 ml per hour. After intravenous injection of erythrocytes damaged by incubation with N-ethylmaleimide, CO was produced in excess of base-line production for 3 to 4 hours with an average yield of 0.89 + (SE) 0.046 umole of carbon monoxide to 1 Mmole of heme degraded.After intravenous injection of N-ethylmaleimide (NEM)-treated erythrocytes containing hemoglobin labeled with 14carbon, 14CO was produced. Its specific activity was approximately one-eighth that of the injected heme. It was also produced after intravenous injection of solutions of hemoglobin-14C and of reconstituted methemoglobin containing hemin-14C, but not after injections of methemoglobin containing globin-14C. The average yields of 14CO from metabolized heme in the experiments with damaged erythrocytes and hemoglobin solutions were 89 + (SE) 4.6 and 97 + (SE) 17.0%, respectively. These results demonstrate that the CO produced during hemoglobin degradation arises from the heme moiety.The yield of 14CO after injection of hemoglobin-14C solutions decreased significantly to values of 35 and 42% in two experiments when exogenous CO was added to the body stores, resulting in blood carboxyhemoglobin levels of 11.3 and 13.2% saturation. This finding suggests that oxidative metabolism is required during catabolism of hemoglobin to CO and that carboxyhemoglobin levels in this range are sufficient to cause inhibition.After intravenous injection of either hemin-14C or protoporphyrin-14C, 14CO was also produced. After injection of protoporphyrin-14C labeled bilirubin was isolated from gall bladder bile, and labeled hemin was isolated from the liver. It is thus very likely that protoporphyrin is converted to heme before the formation of CO.There was a large difference between the maximal rates of catabolism of hemoglobin to CO observed after injection of damaged erythrocytes and hemoglobin solutions. The limiting parameters in these processes are not yet clear.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 55%

The Production of Carbon Monoxide from Hemoglobin In Vivo*

Coburn¹,

Williams²,

White³

et al. 1967

J. Clin. Invest.

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“…The catabolism of circulating red cell hemoglobin heme (VhemeJ was calculated in micromoles per hr per kg using the formula of White et al (33).…”

Section: Methodsmentioning

confidence: 99%

“…A negative correlation between the excess a chain synthesis and the red cell survival was demonstrated. Interpretation of the 14.6-day erythrocyte 51Cr half-life in the proposita with hemoglobin E-Pthalassemia was complicated by a lack of elution data on hemoglobin E. Pearson (25) (33) reported a decrease in Vco/Vh,,,., from 4.1 to 3.1 postsplenectomy; VCO fell from 94.2 to 64.7 pmol/hr. Similayly, in the proposita with hemoglobin E-P-thalassemia, a drop in VCO from 2.00 to 1.54 pmol/hr/kg was observed after splenectomy.…”

Section: Cr Red Cell Studiesmentioning

confidence: 99%

Splenic Sequestration and Ineffective Erythropoiesis in Hemoglobin E-β-Thalassemia Disease

1978

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SummaryA 13-year-old Thai female with hemoglobin E-/3-thalassemia was evaluated for anemia and splenomegaly. Globin chain synthesis in a whole cell system revealed an absence of PA chains and excessive a chains. The a/PE + y ratio was 1.26 in bone marrow and 1.90 in peripheral blood. The average y/PE ratio in bone marrow and peripheral blood was 0.36 compared to peripheral blood concentrations of 49% hemoglobin E and 51% hemoglobin F. Homologous red cell 51Cr half-life increased from 22.7 days to 32.8 days after splenectomy. Total circulating hemoglobin increased from 112.9 to 149.7 g. Endogenous carbon monoxide productive (Vco) as a measure of total heme catabolism decreased from 2.00 to 1.54 pmol/hr/kg, Ineffective erythropoiesis was manifested by an increased Vco/Vheme., ratio of 7.52. SpeculationSplenic sequestration may occur as a complicating factor in the anemia of hemoglobin E-P-thalassemia. The mechanism of this disorder is probably related to excessive a chain production and hemoglobin E instability.

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“…Biological production of carbon monoxide has been reported in algae (3,7), in fungi (16), in higher plants (10,18), in siphonophores (19), and in man (12,17). It is now well established that during the breakdown of hemoglobin in senescent erythrocytes in humans, the heme ring is cleaved by removal of the a-methyne bridge carbon which is then oxidized to CO with the concomitant formation of bile pigment and iron (13).…”

mentioning

confidence: 99%

An Inexpensive Technique for Measuring Carbon Monoxide Formation in Plants

Troxler

1971

Plant Physiol.

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Biological production of carbon monoxide has been reported in algae (3, 7), in fungi (16), in higher plants (10,18), in siphonophores (19), and in man (12,17). It is now well established that during the breakdown of hemoglobin in senescent erythrocytes in humans, the heme ring is cleaved by removal of the a-methyne bridge carbon which is then oxidized to CO with the concomitant formation of bile pigment and iron (13). Recent work in this laboratory has shown that during the formation of phycocyanobilin, equimolar quantities of CO are similarly produced (15). Although CO can be measured by mass spectrometry (2), by gas chromatography (5), or by nondispersive infrared analysis (1), these methods require the availability of costly equipment and preclude certain kinds of metabolic experimentation on CO biosynthesis from radiolabeled precursors. The present paper describes, therefore, an inexpensive method for determining biological CO production in algae, which is generally adaptable to studies on CO formation in plants. Figure 1A. At 4-to 15-hr intervals, estimates of phycocyanobilin synthesized in the suspension (9) and of CO present in the gas reservoir were made. MATERIALS AND METHODSCO Measurement. CO accumulated in the gas reservoir was passed through the train assembly shown in Figure lB RESULTS AND DISCUSSION The train shown in Figure 1B is designed to measure CO as catalytically derived CO2 after removal of CO2 (not derived) from the sample gas. In calibration experiments, 22.3 and 44.6 t-moles of CO, representing 0.5 and 1.0 ml of the pure gas, were injected with a tuberculin syringe into 95% 02-5% CO., contained in a 2-liter glass suction flask. The sample gas was then forced through the train by displacement from the flask with water. Under these conditions, recoveries of CO as derived CO2 exceeded 95% (Table I). Titration of alkali in the test trap (VI) preceding the Hopcalite catalyst (VIII) revealed that bicarbonate was lacking, which shows that the Baralyme, Ascarite, and NaOH absorbers had efficiently removed CO. from the gas sample.For calibration of the train with "CO standards (New England Nuclear, Boston, Mass.; 4.5 mc/mmole) radiolabeled CO was mixed with carrier gas as above and passed through the train. The disintegrations per minute in derived "CO2 were determined by driving "C-labeled bicarbonate from solution after titration of the residual alkali in the terminal traps (IX) to pH 8.5. "CO.. was collected in 5 ml of ethanolamine-methoxvethanol (2:1) and counted in 15 ml of toluene-methoxyethanol (2:1) containing 4 g/liter of 2,5-bis-2(tertiarybutylbenzoxazolyl)-,B-thiophene (Packard Instrument Co., Downers Grove. Ill.). All counting was done in a Tri-Carb liquid scintillation spectrometer. and the quench in each vial was determined by the addition of toluene-"C internal standard.The recovery of 33.0 and 34.0 1cmoles of "CO placed in 2 liters of 95%-0-5%o CO. and passed through the train was 376 www.plantphysiol.org on May 8, 2018 -Published by Downloaded from

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Carbon Monoxide Production Associated with Ineffective Erythropoiesis*

Cited by 52 publications

References 36 publications

The Production of Carbon Monoxide from Hemoglobin In Vivo*

The Production of Carbon Monoxide from Hemoglobin In Vivo*

Splenic Sequestration and Ineffective Erythropoiesis in Hemoglobin E-β-Thalassemia Disease

An Inexpensive Technique for Measuring Carbon Monoxide Formation in Plants

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