PET is Wonderful Annual Meeting 2021 Oct 26, 2021 12:00 AM — Virtual Meeting (online)
NRS Mental Health Network Annual Scientific Meeting 2021 Nov 02, 2021 09:00 AM - 05:00 PM — Royal College of Physicians, Edinburgh (and online)
SRS Autumn Meeting 2021 Nov 12, 2021 08:30 AM - 04:00 PM — Dundee

eLearning

SINAPSE experts from around Scotland have developed ten online modules designed to explain medical imaging. They are freely available and are intended for non-specialists.


Edinburgh Imaging Academy at the University of Edinburgh offers the following online programmes through a virtual learning environment:

Neuroimaging for Research MSc/Dip/Cert

Imaging MSc/Dip/Cert

PET-MR Principles & Applications Cert

Applied Medical Image Analysis Cert

Online Short Courses

Enantiomers of 4-amino-3-fluorobutanoic acid as substrates for gamma-aminobutyric acid aminotransferase. Conformational probes for GABA binding

Author(s): M. D. Clift, H. T. Ji, G. P. Deniau, D. O'Hagan, R. B. Silverman

Abstract:
gamma-Aminobutyric acid aminotransferase (GABA-AT), a pyridoxal 5'-phosphate dependent enzyme, catalyzes the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) to succinic semialdehyde with concomitant conversion of pyridoxal, 5'-phosphate (PLP) to pyridoxamine 5'-phosphate (PMP). The enzyme then catalyzes the conversion of a.-ketoglutarate to the excitatory neurotransmitter L-glutamate. Racemic 4-amino-3-fluorobutanoic acid (3-F-GABA) was shown previously to act as a substrate for GABA-AT, not for transamination, but for HF elimination. Here we report studies of the reaction catalyzed by GABA-AT on (R)- and (S)-3-F-GABA. Neither enantiomer is a substrate for transamination. Very little elimination from the (S)-enantiomer was detected using a coupled enzyme assay; The rate of elimination of HF from the (R)-enantiomer is at least 10 times greater than that for the (S)-enantiomer. The (R)-enantiomer is about 20 times more efficient as a substrate for GABA-AT catalyzed HF elimination than GABA is a substrate for transamination. The (R)-enantiomer also inhibits the transamination of GABA 10 times more effectively than the (S)-enantiomer. Using a combination of computer modeling and the knowledge that vicinal C-F and C-NH3+ bonds have a strong preference to align gauche rather than anti to each other, it is concluded that on binding of free 3-F-GABA to GABA-AT the optimal conformation places the C-NH3+ and C-F bonds gauche in the (R)-enantiomer but anti in the (S)-enantiomer. Furthermore, the dynamic binding process and the bioactive conformation of GABA bound to GABA-AT have been inferred on the basis of the different biological behavior of the two enantiomers of 3-F-GABA when they bind to the enzyme. The present study suggests that the C-F bond can be utilized as a conformational probe to explore the dynamic binding process and provide insight into the bioactive conformation of substrates, which cannot be easily determined by other biophysical approaches.

Full version: Available here

Click the link to go to an external website with the full version of the paper


ISBN: 0006-2960
Publication Year: 2007
Periodical: Biochemistry
Periodical Number:
Volume: 46
Pages: 13819-13828
Author Address: