Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions

Beerstecher, Ernest; Shive, William

doi:10.1016/s0021-9258(17)35140-2

Cited by 27 publications

(4 citation statements)

References 11 publications

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“…It inhibits growth by 50% at molar concentrations which constitute only about 33.3-1.25% those of glutamate (see Table IV). These results are in contrast to those with the other common amino acid antagonists where the concentrations needed for inhibition often exceed that of the natural amino acid by 10-to 100-fold (Ames, 1964;Surdin et al, 1965;Rabinowitz et al, 1954;Beerstecher, 1954;Beerstecher and Shive, 1947;Harding and Shive, 1948).…”

Section: Discussionmentioning

confidence: 65%

“…Both -W-oxalyl and /3-TV-oxaIyl derivatives of ,ßdiaminopropionic acid are reported to occur naturally (Roy and Rao, 1968). Bell and O'Donovan (1966) also report that the a-M-oxalyl isomer is formed by rearrangement of the d-TV-oxalyl isomer under mild conditions. Toxicity of the a-M-oxalyl isomer has not been evaluated.…”

Section: Discussionmentioning

confidence: 86%

“…(For composition of thinlayer chromatography solvents, see Table I.) It was free of a-TV-oxalyl-L-,/3-diaminopropionic acid as indicated by homogeneity in high-voltage electrophoresis at pH 3.6 (Bell and O'Donovan, 1966;Bell and Tirimanna, 1965). After recrystallization from hot, distilled water, a product was obtained in 4-10% yield which melted at 204.5-206°dec.…”

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confidence: 99%

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Specificity of the neurotoxin from Lathyrus sativus as an amino acid antagonist

Mehta¹,

Hsu²,

Haskell³

1972

Biochemistry

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This paper reports evidence that a neurotoxin from the pulse Lathyrus sativus behaves as a potent amino acid antagonist in certain microorganisms. The toxin was isolated in 1963 from Lathyrus sativus seeds. Consumption of these seeds as a major calorie source has long been associated with outbreaks of the paralytic human disease known as neurolathyrism. The toxin was assigned the structure ß-oxalyl-L-a,/3-diaminopropionic acid. This paper describes work to confirm the structure of the toxin and to determine its specificity as an amino acid antagonist. The toxin depresses c X^Vonsumption of Lathyrus peas has been associated for more than 2000 years with a crippling human disease now known as neurolathyrism. (For recent reviews, see Padmanaban, 1969, andRao et al., 1969.) Three research groups in India (Murti et al., 1964;Roy et al., 1963;Rao et al., 1964) have reported the isolation of a neurotoxin from Lathyrus sativus seeds. The toxin produces muscle tremors, paralysis of the legs, and convulsions when injected into animals with an immature or damaged blood-brain barrier (Rao and Sarma, 1967) or when introduced intrathecally into adult monkeys . The toxin was assigned the structure /3-7V-oxaIyl-L-a,/3-diaminopropionic acid (Rao et al., 1964;Murti et al., 1964), and its possible role as the cause of human neurolathyrism was suggested.Conclusive evidence that human neurolathyrism is due solely to /3-A-oxalyl-L-a,0-diaminopropionic acid is lacking. However, the compound warrants investigation because of its demonstrated neurotoxic properties.The structural similarity of the toxin to common amino acids suggested to us that its neurotoxicity may stem from a possible role as an amino acid antagonist. This paper describes work to confirm the structure of the toxin and to determine the specificity of the toxin as an amino acid antagonist. Materials and MethodsSynthetic Toxin. All microbiological experiments described in this paper were carried out with highly purified synthetic toxin prepared from the copper chelate of L-a,/3-diaminopropionic acid and ethyl oxalyl chloride. L-a,/3-Diaminopropionic acid (Calbiochem, La Jolla, Calif.) was converted to a copper chelate as described by Rao et al., 1964. Ethyl oxalyl chloride was synthesized in about 85% yield with f From the

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

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Specificity of the neurotoxin from Lathyrus sativus as an amino acid antagonist

Mehta¹,

Hsu²,

Haskell³

1972

Biochemistry

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“…Antagonists of phenylalanine were chosen for the initial study because the metabolic pathways of this amino acid are more restricted. #-2-Thienyl-DL-alanine was selected because of the extensive background of microbiological data on its antagonism to phenylalanine (2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

TRANSAMINATION IN THE METABOLISM OF SS-2-Thienyl-Dl-Alanine IN NORMAL AND NEOPLASTIC CELLS IN VITRO

Jacquez

Barclay

Stock

1952

Journal of Experimental Medicine

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In tissue cultures of C-57 black mouse heart and sarcoma T-241, ß-2-thienyl-DL-alanine acts specifically as a phenylalanine antagonist. Heart cultures can transaminate between ß-2-thienyl-DL-alanine and phenylpyruvate to form L-phenylalanine and thus block the toxic action of the remaining ß-2-thienyl-DL-alanine, whereas sarcoma T-241 cultures cannot. Of eleven mouse tumors and four rat tumors tested for their ability to perform this reaction, nine tumors had little or no activity. The ß-2-thienylpyruvic acid resulting from transamination further reacts to form a red compound the exact structure of which is not yet known.

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Intermediates in Amino Acid Biosynthesis

Davis¹

1955

Advances in Enzymology - And Related Areas of Molecular Biology

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Biochemical Transformations as Determined by Competitive Analogue-Metabolite Growth Inhibitions

Cited by 27 publications

References 11 publications

Specificity of the neurotoxin from Lathyrus sativus as an amino acid antagonist

Specificity of the neurotoxin from Lathyrus sativus as an amino acid antagonist

TRANSAMINATION IN THE METABOLISM OF SS-2-Thienyl-Dl-Alanine IN NORMAL AND NEOPLASTIC CELLS IN VITRO

Intermediates in Amino Acid Biosynthesis

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