Myeloperoxidase of the leucocyte of normal human blood

Schultz, Julius; Corlin, Richard F.; Oddi, Frederick; Kaminker, Kenneth; Jones, Walter

doi:10.1016/0003-9861(65)90324-3

Cited by 76 publications

(25 citation statements)

References 13 publications

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“…Melatonin is cleaved in vivo either by monocytes [31,32] or by activated macrophages [33]. The identity of the enzyme involved in this process is still unknown.…”

Section: Oxidative Metabolism Of Melatoninmentioning

confidence: 99%

Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase

Ferry

Ubeaud

Lambert³

et al. 2005

Biochemical Journal

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The catabolism of melatonin, whether naturally occurring or ingested, takes place via two pathways: ∼ 70 % can be accounted for by conjugation (sulpho-and glucurono-conjugation), and ∼ 30 % by oxidation. It is commonly thought that the interferoninduced enzyme indoleamine 2,3-dioxygenase (EC 1.13.11.42), which oxidizes tryptophan, is also responsible for the oxidation of 5-hydroxytryptamine (serotonin) and its derivative, melatonin. Using the recombinant enzyme expressed in Escherichia coli, we show in the present work that indoleamine 2,3-dioxygenase indeed cleaves tryptophan; however, under the same conditions, it is incapable of cleaving the two other indoleamines. By contrast, myeloperoxidase (EC 1.11.1.7) is capable of cleaving the indole moiety of melatonin. However, when using the peroxidase conditions of assay -with H 2 O 2 as co-substrate -indoleamine 2,3-dioxygenase is able to cleave melatonin into its main metabolite, a kynurenine derivative. The present work establishes that the oxidative metabolism of melatonin is due, in the presence of H 2 O 2 , to the activities of both myeloperoxidase and indoleamine 2,3-dioxygenase (with lower potency), since both enzymes have K m values for melatonin in the micromolar range. Under these conditions, several indolic compounds can be cleaved by both enzymes, such as tryptamine and 5-hydroxytryptamine. Furthermore, melatonin metabolism results in a kynurenine derivative, the pharmacological action of which remains to be studied, and could amplify the mechanisms of action of melatonin.

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“…Melatonin is cleaved in vivo either by monocytes [31,32] or by activated macrophages [33]. The identity of the enzyme involved in this process is still unknown.…”

Section: Oxidative Metabolism Of Melatoninmentioning

confidence: 99%

Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase

Ferry

Ubeaud

Lambert³

et al. 2005

Biochemical Journal

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“…The remaining cells were sonicated [14] in 2 ml batches and centrifuged at 600 X g for 10 min to remove unbroken cells and nuclei. Supernatants were combined and centrifuged at 4000 X g for 10 min to yield a light green, dense pellet representing the "lysosomal" fraction [23]; the pellet was taken up in 20% sucrose (with or without EDTA) and, after a second centrifugation for 10 min at 4000 X g, was subjected to 10 freeze-thaw cycles as above. Supernatant fractions decanted from the 4000 x g centrifugations were combined and centrifuged at 100,000 X g for 30-60 min [38,39].…”

Section: Preparation Of Leukocyte Fractionsmentioning

confidence: 99%

Enzymic Reduction of Cystine by Subcellular Fractions of Cultured and Peripheral Leukoyctes from Normal and Cystinotic Individuals

1972

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ExtractLysates of cultured and freshly drawn isolated peripheral leukocytes from normal and cystinotic individuals were examined for cystine-reducing activity, with particular emphasis on possible enzyme action in lysosome-containing fractions. Whole cell extracts of cultured leukocytes were found to possess strong glutathione-cystine transhydrogenase activity at both pH 7.5 and 5.5; no significant difference in this enzyme activity between extracts of normal and cystinotic cells was observable at either pH. Subcellular fractionation of these cultured leukocytes indicated that the major portion of transhydrogenase activity in the 5.5-7.5 pH range was confined to the highspeed supernatant (cytoplasmic) fraction, with little or no activity being detectable in the granular fractions. Comparative enzyme assays at both pH 4.5 and 7.5 with lysosomal and supernatant fractions of peripheral leukocytes freshly drawn from normal and cystinotic donors were consistent with the foregoing results in terms of the subcellular distribution of glutathione-cystine transhydrogenase activity; again there appeared to be no significant difference in the transhydrogenase activities of these fractions from normal and cystinotic leukocytes at either pH. The relation of these observations to the pathogenesis of cystinosis is discussed. Speculation

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“…Normal neutrophils contain the lysosomal enzyme myeloperoxidase (MPO) in amounts that may approximate 5% of their dry weight (2)(3)(4). First detected in pus over a century ago (5), MPO has since been purified and extensively studied (6, 7); however, its metabolic functions are incompletely defined.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection

Lehrer¹,

Cline²

1969

J. Clin. Invest.

666

278

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A B S T R A C T The neutrophils and monocytes of a patient with disseminated candidiasis were found to lack detectable levels of the lysosomal enzyme myeloperoxidase (MPO), although they had normal levels of other granule-associated enzymes. Leukocytes from one of the patient's sisters also lacked detectable MPO; leukocytes from his four sons contained approximately one-third of mean normal peroxidase levels. Neither the patient nor his affected relatives had experienced frequent or unusual bacterial infections.The phagocytic activity of the patient's MPO-deficient neutrophils was intact, and the cells displayed normal morphologic and metabolic responses to phagocytosis. In contrast to normal leukocytes which killed 30.5 ±7.3% of ingested Candida albicans in 1 hr, however, the patient's neutrophils killed virtually none. His leukocytes also failed to kill the strain of C. albicans recovered from his lesions, as well as other Candida. species. These MPO-deficient neutrophils killed Serratia marcescens and Staphylococcus aureus 502A at an abnormally slow rate, requiring 3-4 hr to achieve the bactericidal effect attained by normal leukocytes after 45 min. No other abnormalities in his cellular or humoral immune responses were demonstrated.These findings suggest that hereditary MPO deficiency is transmitted as an autosomal recessive characteristic, that the homozygous state conveys enhanced susceptibility to disseminated candidiasis, and that MPO is necessary for candidacidal activity in human neutrophils.This work was presented in part at the National Meeting of the American Federation for Clinical Research, Atlantic City, N. J., and published in abstract form (1).

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Myeloperoxidase of the leucocyte of normal human blood

Cited by 76 publications

References 13 publications

Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase

Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase

Enzymic Reduction of Cystine by Subcellular Fractions of Cultured and Peripheral Leukoyctes from Normal and Cystinotic Individuals

Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection

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