دورية أكاديمية
أعرض في EDS

Fluorination at the 4 position alters the substrate behavior of L-glutamine and L-glutamate: Implications for positron emission tomography of neoplasias.

التفاصيل البيبلوغرافية
العنوان: Fluorination at the 4 position alters the substrate behavior of L-glutamine and L-glutamate: Implications for positron emission tomography of neoplasias.
المؤلفون: Jeitner TM; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA., Kristoferson E; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA., Azcona JA; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA., Pinto JT; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA., Stalnecker C; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA., Erickson JW; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA., Kung HF; Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Li J; Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA., Ploessl K; Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA., Cooper AJL; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
المصدر: Journal of fluorine chemistry [J Fluor Chem] 2016 Dec; Vol. 192 (A), pp. 58-67. Date of Electronic Publication: 2016 Oct 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Sequoia Sa Country of Publication: United States NLM ID: 0373322 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-1139 (Print) Linking ISSN: 00221139 NLM ISO Abbreviation: J Fluor Chem Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: Lausanne : Elsevier Sequoia Sa
Original Publication: Lausanne, Elsevier Sequoia S.A.
مستخلص: Two 4-fluoro-L-glutamine diastereoisomers [(2 S ,4 R )-4-FGln, (2 S ,4 S )-4-FGln] were previously developed for positron emission tomography. Label uptake into two tumor cell types was greater with [ 18 F](2 S ,4 R )-4-FGln than with [ 18 F](2 S ,4 S )-4-FGln. In the present work we investigated the enzymology of two diastereoisomers of 4-FGln, two diastereoisomers of 4-fluoroglutamate (4-FGlu) (potential metabolites of the 4-FGln diastereoisomers) and another fluoro-derivative of L-glutamine [(2 S ,4 S )-4-(3-fluoropropyl)glutamine (FP-Gln)]. The two 4-FGlu diastereoisomers were found to be moderate-to-good substrates relative to L-glutamate of glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase. Additionally, alanine aminotransferase was shown to catalyze an unusual γ-elimination reaction with both 4-FGlu diastereoisomers. Both 4-FGlu diastereoisomers were shown to be poor substrates, but strong inhibitors of glutamine synthetase. Both 4-FGln diastereoisomers were shown to be poor substrates compared to L-glutamine of glutamine transaminase L and α-aminoadipate aminotransferase. However, (2 S ,4 R )-4-FGln was found to be a poor substrate of glutamine transaminase K, whereas (2 S ,4 S )-4-FGln was shown to be an excellent substrate. By contrast, FP-Gln was found to be a poor substrate of all enzymes examined. Evidently, substitution of H in position 4 by F in L-glutamine/L-glutamate has moderate-to-profound effects on enzyme-catalyzed reactions. The present results: 1) show that 4-FGln and 4-FGlu diastereoisomers may be useful for studying active site topology of glutamate- and glutamine-utilizing enzymes; 2) provide a framework for understanding possible metabolic transformations in tumors of 18 F-labeled (2 S ,4 R )-4-FGln, (2 S ,4 S )-4-FGln, (2 S ,4 R )-4-FGlu or (2 S ,4 S )-4-FGlu; and 3) show that [ 18 F]FP-Gln is likely to be much less metabolically active in vivo than are the [ 18 F]4-FGln diastereoisomers.
Competing Interests: The authors declare no conflict of interest
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معلومات مُعتمدة: R01 CA164490 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Fluoroglutamate; Fluoroglutamine; Glutamate-utilizing enzymes; Glutamine-utilizing enzymes
تواريخ الأحداث: Date Created: 20170527 Latest Revision: 20191120
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC5440087
DOI: 10.1016/j.jfluchem.2016.10.008
PMID: 28546645
قاعدة البيانات: MEDLINE
الوصف
تدمد:0022-1139
DOI:10.1016/j.jfluchem.2016.10.008