Disease relevance of Methional

• Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis [1].
• Developmental toxicity study with 3-(methylthio)propionaldehyde vapor by whole-body exposure of Sprague-Dawley rats [2].
• Only Lactococcus lactis IFPL730 produced high amounts of methional [3].

High impact information on Methional

• Rat liver microsomes generate methane from dimethyl sulfoxide and ethylene from either methional or 2-keto-4-thiomethylbutyric acid during electron transfer initiated by reduced nicotinamide-adenine dinucleotide phosphate (NADPH) [4].
• Ethylene production required the presence of neutrophils, opsonized zymosan, and methional, indicating that it was formed from methional by stimulated but not resting neutrophils [5].
• Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it [6].
• A mechanism has been devised which accounts for the self-deactivation phenomenon, the effect of phenol and methional, the disulfide at the active site, and the pathway of substrate oxygenation [7].
• Free (*) OH scavengers did not inhibit the DNA damage, although methional did inhibit it [8].

Chemical compound and disease context of Methional

• Conversion of methionine to methional by Lactococcus lactis [3].
• Evaluation of the role of methional, 2-keto-4-methylthiobutyric acid and peroxidase in ethylene formation by Escherichia coli [9].

Biological context of Methional

• These results support a role of cellular methional and malondialdehyde in apoptosis [10].
• The extent of DNA fragmentation in BAF3 bcl2 cells approached that in BAF3 b0 cells in the presence of quercetin and exogenous methional, suggesting a defect in methional biosynthesis in BAF3 bcl2 cells [11].
• These observations on G2/M-synchronized cells are different from those seen in BAF3b0 cells in G1 phase, 3 h after their release from the G2/M block, in that there was no decrease in size of the G1 population even after an additional 4 h incubation in the presence of methional [12].
• In contrast, when BAF3 b0 cells were synchronized in G2/M phase using SK&F 96365, and treated with methional immediately after drug removal, methional induced DNA-strand breaks in 49% of cells in 4 h, compared to 12% in controls [12].
• On the other hand, methional, a deamination and decarboxylation product of methionine, was highly cytotoxic [13].

Anatomical context of Methional

• Altered methional homoeostasis is associated with decreased apoptosis in BAF3 bcl2 murine lymphoid cells [11].
• Stimulated human alveolar macrophages were demonstrated to oxidize B-methyl proprionaldehyde (methional) or 2-keto-4-thiomethylbutyric acid to ethylene (C2H4) [14].
• The effect of methional on prostaglandin biosynthesis from 5,8,11,14-eicosatetraenoic acid was studied with microsomes from both bovine vesicular glands (BVG) and sheep vesicular glands (SVG) [15].
• Prostaglandin biosynthesis from eicosa-8, 11, 14-trienoic acid in microsomes from bovine seminal vesicles is inhibited by relatively high concentrations of hydroxyl radical scavengers: dimethyl sulfoxide, n- and t-butanol, and methional [16].
• We report a Phase I study in 39 cancer patients of the tolerance and biologic activity of 47 intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) treatments with recombinant methional gamma interferon (IFN-gamma 4A) which most closely resembles the natural material produced by T lymphocytes [17].

Associations of Methional with other chemical compounds

• Typical hydroxyl radical scavengers did not inhibit N-acetylcysteine plus Cu(II)-induced DNA damage, whereas methional completely inhibited it [18].
• Methionine and methional inhibited the DNA damage completely [19].
• In contrast, the addition of quercetin (an inhibitor of aldehyde reductase) in an attempt to diminish methional reduction increased apoptosis in both BAF3 b0 and BAF3 bcl2 cells [11].
• The addition of disulfiram (an inhibitor of aldehyde dehydrogenase) in order to reduce methional oxidation brought about an increase in apoptosis in BAF3 b0 but not in BAF3 bcl2 cells [11].
• Scavengers of singlet oxygen (1O2), such as sodium azide and methional, inhibited DNA damage [20].

Gene context of Methional

• Ethylene generation was shown to be inhibited by superoxide dismutase, catalase, and scavengers of OH.. Of the cells examined, PMN generated the most ethylene from methional, exhibiting a fourfold increase during phagocytosis [21].
• In these cells transfected with the bcl2 gene, BAF3 bcl2, the apoptotic-inducing activity of methional is dramatically reduced [11].
• Methional is a potent inducer of apoptosis in an interleukin 3-dependent murine lymphoid cell line BAF3 b0 when it is added to the culture medium [11].
• Bathocuproine, a Cu(I)-specific chelator, catalase and methional inhibited the DNA damage by quercetin, whereas free hydroxyl radical scavengers did not [22].
• The methional level in baked tubers of field-grown transgenic potato lines was increased between 2.4- and 4.4-fold in lines CGS1, CGS2, and CGS4 [23].

Analytical, diagnostic and therapeutic context of Methional

• Reactions of oxygen radical species with methional: a pulse radiolysis study [24].
• The inhibitory effect of 10 mM methional was reversed by lyophilization [15].
• The binding of sarcoplasmic and myofibrillar proteins extracted from postrigor pork muscle and from 7 and 12 months dry-cured hams with volatile compounds such as 3-methyl-butanal, 2-methyl-butanal, 2-pentanone, hexanal, methional, and octanal was studied using solid phase microextraction and gas chromatography analysis [25].

References