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Chemical Compound Review:

AC1L3ONE 2,5-diamino-6-fluoro-hexanoic acid

Synonyms: CTK8H3557, 116292-10-5, 5-Fluoromethylornithine, 5-Amino-6-fluoronorleucine, Norleucine, 5-amino-6-fluoro-, ...

Sarhan, S. et al., Kaneko, S. et al., Bolkenius, F.N. et al., Ando, A. et al., Seiler, N. et al., et al.

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Disease relevance of 5-Fluoromethylornithine

PURPOSE: A prior study showed inactivation of ornithine-delta-aminotransferase (OAT)-deficient human retinal pigment epithelial (RPE) cells by a specific irreversible inhibitor (5-fluoromethylornithine; 5-FMO) leading to cell death, in an in vitro model of gyrate atrophy (GA) of the choroid and retina [1].
METHODS: Human RPE cells, human hepatoma cells, and human fibroblast cells were treated with 5-fluoromethylornithine (5-FMOrn), a specific irreversible inhibitor of OAT [2].
The protective effects of combinations of 5-fluoromethylornithine (5FMOrn), a selective inhibitor of ornithine aminotransferase, and of compounds known to antagonize ammonia toxicity, were studied in acute, lethal ammonia intoxication in mice [3].
Administration of 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase (OAT), significantly reduced mortality, and it ameliorated most of the TAA-induced pathologic symptoms, such as hypothermia, decreased locomotor and exploratory behavior, pathologic liver function and amino acid patterns [4].

High impact information on 5-Fluoromethylornithine

It is proposed that the neutralization of the active site Arg413 by a salt bridge with Glu235 also plays an important role in productive binding of both 5-fluoromethylornithine and l-ornithine [5].
5-Fluoromethylornithine (5FMOrn) is an enzyme-activated irreversible inhibitor or ornithine aminotransferase (L-ornithine:2-oxo-acid 5-aminotransferase, OAT) [6].
DL-canaline and 5-fluoromethylornithine. Comparison of two inactivators of ornithine aminotransferase [6].
We recently showed that ornithine exhibits cytotoxicity to human retinal pigment epithelial (RPE) cell lines treated with the OAT inhibitor, 5-fluoromethylornithine (5-FMOrn), and suggested that this system may be an in vitro model of gyrate atrophy [7].
Selective inactivation of ornithine aminotransferase (OAT) by 5-fluoromethylornithine raises endogenous ornithine concentrations so that citrulline formation is effectively catalysed by the aberrant OCT, in spite of its low affinity for ornithine [8].

Analytical, diagnostic and therapeutic context of 5-Fluoromethylornithine

Effects of ornithine aminotransferase inactivation by 5-fluoromethylornithine in rats following portacaval anastomosis [9].

References

Cytotoxic effect of spermine on retinal pigment epithelial cells. Kaneko, S., Ueda-Yamada, M., Ando, A., Matsumura, S., Okuda-Ashitaka, E., Matsumura, M., Uyama, M., Ito, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
Prevention of ornithine cytotoxicity by proline in human retinal pigment epithelial cells. Ueda, M., Masu, Y., Ando, A., Maeda, H., Del Monte, M.A., Uyama, M., Ito, S. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
Protection against lethal ammonia intoxication: synergism between endogenous ornithine and L-carnitine. Sarhan, S., Knoedgen, B., Seiler, N. Metabolic brain disease. (1994) [Pubmed]
Effects of inhibition of ornithine aminotransferase on thioacetamide-induced hepatogenic encephalopathy. Sarhan, S., Knödgen, B., Grauffel, C., Seiler, N. Neurochem. Res. (1993) [Pubmed]
Crystal structure of human ornithine aminotransferase complexed with the highly specific and potent inhibitor 5-fluoromethylornithine. Storici, P., Capitani, G., Müller, R., Schirmer, T., Jansonius, J.N. J. Mol. Biol. (1999) [Pubmed]
DL-canaline and 5-fluoromethylornithine. Comparison of two inactivators of ornithine aminotransferase. Bolkenius, F.N., Knödgen, B., Seiler, N. Biochem. J. (1990) [Pubmed]
Heterogeneity in ornithine cytotoxicity of bovine retinal pigment epithelial cells in primary culture. Ando, A., Ueda, M., Uyama, M., Masu, Y., Okumura, T., Ito, S. Exp. Eye Res. (2000) [Pubmed]
Decreased hyperammonaemia and orotic aciduria due to inactivation of ornithine aminotransferase in mice with a hereditary abnormal ornithine carbamoyltransferase. Seiler, N., Grauffel, C., Daune-Anglard, G., Sarhan, S., Knödgen, B. J. Inherit. Metab. Dis. (1994) [Pubmed]
Effects of ornithine aminotransferase inactivation by 5-fluoromethylornithine in rats following portacaval anastomosis. Therrien, G., Sarhan, S., Knödgen, B., Butterworth, R.F., Seiler, N. Metabolic brain disease. (1994) [Pubmed]

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