The PRODUCTION OF Β-Nitropropionic ACID BY a STRAIN OF ASPERGILLUS FLAVUS

Bush, Milton T.; Touster, Oscar; Brockman, Jean.Early.

doi:10.1016/s0021-9258(19)77741-2

Cited by 83 publications

(14 citation statements)

References 11 publications

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“…Whereas itaconate shares a similar acidity with succinate, the C-3 protons of 3-NP have a pK of 9.1. 32 Because of this acidity, it has been suggested that the conjugate base, propionate-3nitronate, serves as the true inhibitor by mimicking the aci form of the succinate trianion intermediate. 10 3-NP has previously been characterized as a slow-binding inhibitor of ICL, displaying a time-dependent increase in the level of inhibition.…”

Section: ■ Resultsmentioning

confidence: 99%

Cysteine Is the General Base That Serves in Catalysis by Isocitrate Lyase and in Mechanism-Based Inhibition by 3-Nitropropionate

Moynihan

Murkin

2013

Biochemistry

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Isocitrate lyase (ICL) catalyzes the reversible cleavage of isocitrate into succinate and glyoxylate. It is the first committed step in the glyoxylate cycle used by some organisms, including Mycobacterium tuberculosis, where it has been shown to be essential for cell survival during chronic infection. The pH-rate and pD-rate profiles measured in the direction of isocitrate synthesis revealed solvent kinetic isotope effects (KIEs) of 1.7 ± 0.4 for (D2O)V and 0.56 ± 0.07 for (D2O)(V/Ksuccinate). Whereas the (D2O)V is consistent with partially rate-limiting proton transfer during formation of the hydroxyl group of isocitrate, the large inverse (D2O)(V/Ksuccinate) indicates that substantially different kinetic parameters exist when the enzyme is saturated with succinate. Inhibition by 3-nitropropionate (3-NP), a succinate analogue, was found to proceed through an unusual double slow-onset process featuring formation of a complex with a Ki of 3.3 ± 0.2 μM during the first minute, followed by formation of a final complex with a Ki* of 44 ± 10 nM over the course of several minutes to hours. Stopped-flow measurements during the first minute revealed an apparent solvent KIE of 0.40 ± 0.03 for association and unity for dissociation. In contrast, itaconate, a succinate analogue lacking an acidic α-proton, did not display slow-binding behavior and yielded a (D2O)Ki of 1.0 ± 0.2. These results support a common mechanism for catalysis with succinate and inhibition by 3-NP featuring (1) an unfavorable prebinding isomerization of the active site Cys191-His193 pair to the thiolate-imidazolium form, a process that is favored in D2O, and (2) the transfer of a proton from succinate or 3-NP to Cys191. These findings also indicate that propionate-3-nitronate, which is the conjugate base of 3-NP and the "true inhibitor" of ICL, does not bind directly and must be generated enzymatically.

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Section: ■ Resultsmentioning

confidence: 99%

Cysteine Is the General Base That Serves in Catalysis by Isocitrate Lyase and in Mechanism-Based Inhibition by 3-Nitropropionate

Moynihan

Murkin

2013

Biochemistry

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“…Apparently the dye acid (or the dye base) is being extracted by benzene (3) and the color change is due to salt formation. For the Rose Bengal reagent this explanation fits, except that it is dif-ficult to understand why the maximum sensitivity is obtained by extraction near pH 4 (pH 3 for Erythrosin J), extraction at a lower pH producing a slightly less sensitive reagent. It may well be that at lower pH values minute amounts of acids from the buffer are extracted into benzene, thus reducing the sensitivity of the reagent.…”

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confidence: 94%

Spectrophotometric Determination of 3-Nitropropanoic Acid in Biological Extracts

Matsumoto¹,

Unrau²,

Hylin³

et al. 1961

Anal. Chem.

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“…Compounds containing a nitro functionality are relatively rare among natural products (16). Higher plants (17) and fungi (18)(19)(20) have been reported to produce nitro-containing secondary metabolites. Only a few nitro compounds have been isolated from marine organisms, e. g., bryozoans (15,16) and red alga (21).…”

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confidence: 99%

Chemical Constituents of Halophilic Facultatively Anaerobic Bacteria, 1

Schmitz²,

Tanner³

1995

J. Nat. Prod.

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Two new nitrotyramine derivatives, 1 and 2, along with five known aromatic compounds, were isolated from the culture broth of a facultatively anaerobic, halophilic bacterium isolated from a sediment from the Great Salt Plains, Alfalfa County, Oklahoma. The structures of the new compounds were determined from spectral data and were confirmed by synthesis from tyramine hydrochloride. Compound 1 showed cytotoxicity against the murine leukemia P-388 cell line (IC50 3 micrograms/ml).

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The PRODUCTION OF Β-Nitropropionic ACID BY a STRAIN OF ASPERGILLUS FLAVUS

Cited by 83 publications

References 11 publications

Cysteine Is the General Base That Serves in Catalysis by Isocitrate Lyase and in Mechanism-Based Inhibition by 3-Nitropropionate

Cysteine Is the General Base That Serves in Catalysis by Isocitrate Lyase and in Mechanism-Based Inhibition by 3-Nitropropionate

Spectrophotometric Determination of 3-Nitropropanoic Acid in Biological Extracts

Chemical Constituents of Halophilic Facultatively Anaerobic Bacteria, 1

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