Comparative enzymology of (2S,4R)4-fluoroglutamine and (2S,4R)4-fluoroglutamate.

Citation data:

Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, ISSN: 1879-1107, Vol: 163, Issue: 1, Page: 108-20

Publication Year:
2012
Usage 323
Abstract Views 323
Captures 10
Readers 8
Exports-Saves 2
Citations 3
Citation Indexes 3
Repository URL:
https://dx.doi.org/10.1016/j.cbpb.2012.05.010, http://touroscholar.touro.edu/nymc_fac_pubs/70
PMID:
22613816
DOI:
10.1016/j.cbpb.2012.05.010
PMCID:
PMC3389287
Author(s):
Cooper, Arthur J. L., Krasnikov, Boris F, Pinto, John T, Kung, Hank F, Li, Jianyong, Ploessl, Karl
Publisher(s):
Elsevier BV, Touro Scholar
Tags:
Biochemistry, Genetics and Molecular Biology, Alanine Transaminase, Amidohydrolases, Animals, Aspartate Aminotransferases, Glutamate Dehydrogenase, Glutamate-Ammonia Ligase, Glutaminase, Glutamine, Humans, Methionine, Mice, Rats, Biochemistry, Molecular Biology
article description
Many cancer cells have a strong requirement for glutamine. As an aid for understanding this phenomenon the (18)F-labeled 2S,4R stereoisomer of 4-fluoroglutamine [(2S,4R)4-FGln] was previously developed for in vivo positron emission tomography (PET). In the present work, comparative enzymological studies of unlabeled (2S,4R)4-FGln and its deamidated product (2S,4R)4-FGlu were conducted as an adjunct to these PET studies. Our findings are as follows: Rat kidney preparations catalyze the deamidation of (2S,4R)4-FGln. (2,4R)4-FGln and (2S,4R)4-FGlu are substrates of various aminotransferases. (2S,4R)4-FGlu is a substrate of glutamate dehydrogenase, but not of sheep brain glutamine synthetase. The compound is, however, a strong inhibitor of this enzyme. Rat liver cytosolic fractions catalyze a γ-elimination reaction with (2S,4R)4-FGlu, generating α-ketoglutarate. Coupling of a deamidase reaction with this γ-elimination reaction provides an explanation for the previous detection of (18)F(-) in tumors exposed to [(18)F](2S,4R)4-FGln. One enzyme contributing to this reaction was identified as alanine aminotransferase, which catalyzes competing γ-elimination and aminotransferase reactions with (2S,4R)4-FGlu. This appears to be the first description of an aminotransferase catalyzing a γ-elimination reaction. The present results demonstrate that (2S,4R)4-FGln and (2S,4R)4-FGlu are useful analogues for comparative studies of various glutamine- and glutamate-utilizing enzymes in normal and cancerous mammalian tissues, and suggest that tumors may metabolize (2S,4R)4-FGln in a generally similar fashion to glutamine. In plants, yeast and bacteria a major route for ammonia assimilation involves the consecutive action of glutamate synthase plus glutamine synthetase (glutamate synthase cycle). It is suggested that (2S,4R)4-FGln and (2S,4R)4-FGlu will be useful probes in studies of ammonia assimilation by the glutamate synthase pathway in these organisms. Finally, glutamine transaminases are conserved in mammals, plants and bacteria, and probably serve to close the methionine salvage pathway, thus linking nitrogen metabolism to sulfur metabolism and one-carbon metabolism. It is suggested that (2S,4R)4-FGln may be useful in studies of the methionine salvage pathway in a variety of organisms.

This article has 0 Wikipedia mention.