Metabolism of Homocysteine-thiolactone in Plants

Jakubowski, Hieronim; Guranowski, Andrzej

doi:10.1074/jbc.m211819200

Cited by 30 publications

(46 citation statements)

References 31 publications

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“…On the other hand, we observed that the total level of homocysteine was significantly elevated in plasma of patients with invasive breast cancer ( Figure 2D). This observation is consistent with the other earlier observations demonstrating that cultured breast cancer cells produce more homocysteine than normal cells [14]. Gatt et al [15] showed also that hyperhomocysteinemia in women with advanced breast cancer exists.…”

Section: Discussionsupporting

confidence: 82%

Effect of aronia on thiol levels in plasma of breast cancer patients

et al. 2010

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Section: Discussionsupporting

confidence: 82%

Effect of aronia on thiol levels in plasma of breast cancer patients

et al. 2010

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“…[1][2][3]. In each organism examined (bacteria, yeast, plant, mouse, and human) the Hcythiolactone pathway becomes predominant when remethylation or trans-sulfuration reactions are impaired by genetic alterations of enzymes involved in Hcy metabolism, such as cystathionine ␤-synthase (4 -6) and methionine synthase (4,6), or by inadequate supply of folate (5,(7)(8)(9), vitamin B 12 , or vitamin B 6 .…”

Section: Homocysteine (Hcy)mentioning

confidence: 99%

Protective Mechanisms against Homocysteine Toxicity

Zimny

Sikora

Guranowski

et al. 2006

Journal of Biological Chemistry

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Homocysteine (Hcy) editing by methionyl-tRNA synthetase results in the formation of Hcy-thiolactone and initiates a pathway that has been implicated in human disease. In addition to being cleared from the circulation by urinary excretion, Hcythiolactone is detoxified by the serum Hcy-thiolactonase/paraoxonase carried on high density lipoprotein. Whether Hcy-thiolactone is detoxified inside cells was unknown. Here we show that Hcy-thiolactone is hydrolyzed by an intracellular enzyme, which we have purified to homogeneity from human placenta and identified by proteomic analyses as human bleomycin hydrolase (hBLH). We have also purified an Hcy-thiolactonase from the yeast Saccharomyces cerevisiae and identified it as yeast bleomycin hydrolase (yBLH). BLH belongs to a family of evolutionarily conserved cysteine aminopeptidases, and its only known biologically relevant function was deamidation of the anticancer drug bleomycin. Recombinant hBLH or yBLH, expressed in Escherichia coli, exhibits Hcy-thiolactonase activity similar to that of the native enzymes. Active site mutations, C73A for hBLH and H369A for yBLH, inactivate Hcy-thiolactonase activities. Yeast blh1 mutants are deficient in Hcy-thiolactonase activity in vitro and in vivo, produce more Hcy-thiolactone, and exhibit greater sensitivity to Hcy toxicity than wild type yeast cells. Our data suggest that BLH protects cells against Hcy toxicity by hydrolyzing intracellular Hcy-thiolactone.

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“…Aggregates formed by the combination of Hcy thiolactone, a cyclical product of Hcy, with LDL (low-density lipoprotein) were shown to be taken up by intimal macrophages and be incorporated into atheromatous plaques (Naruszewicz et al, 1994). Hcy thiolactone is also incorporated into cellular and secretory proteins through lysine homocysteinylation, leading to the dysfunction of the proteins (Jakubowski, 1997). The high density lipoprotein (HDL) particle(s) is known to prevent the www.intechopen.com formation of ox-LDL by means of the HDL-associated enzyme paraoxonase (PON); its antioxidant properties prevent the accumulation of lipid peroxides on LDL (Shih et al, 1998).…”

mentioning

confidence: 99%

“…The high density lipoprotein (HDL) particle(s) is known to prevent the www.intechopen.com formation of ox-LDL by means of the HDL-associated enzyme paraoxonase (PON); its antioxidant properties prevent the accumulation of lipid peroxides on LDL (Shih et al, 1998). Paraoxonase is a multifunctional antioxidant enzyme that not only can destroy Ox-LDL but also can detoxify the homocysteine metabolite, homocysteine thiolactone (Jakubowski H, 1997). In fact, human paraoxonase possesses a thiolactonase (HTase) activity, hydrolyzing Hcy thiolactone to Hcy (Jakubowski, 1999).…”

mentioning

confidence: 99%