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Metabolic fate of L-(N-13) glutamate in normal isolated myocardium

Conference · · J. Nucl. Med.; (United States)
OSTI ID:6845471
In the present work nitrogen flux of an amino acid in myocardium is followed via arterial bolus injection of non-carrier added L-(N-13)glutamate (N-13 GLU) into the isolated rabbit septa. Incorporation of nitrogen-13 into (N-13)aspartate (N-13 ASP)(16%) and (N-13)alanine (N-13 ALA)(14%) predominates over (N-13)glutamine (N-13 GLN) (3.2%) as determined by reversed phase HPLC in normal septa 6 min after bolus injection. No N-13 ammonia or N-13 urea is detected. Introduction of the transaminase inhibitor aminooxyacetate (AOA, 2 nM) into perfusate completely blocked transaminase reaction and increased N-13 GLN (7.3%) and free N-13 ammonia (4.0%), probably resulting from glutamate dehydrogenase reaction. Inclusion of 2mM pyruvate in the perfusate resulted in 3 fold increase in N-13 ALA (44%), slight increase in N-13 GLN (5.0%) and significant decrease in N-13 ASP. Addition of 2mM AOA in the presence of pyruvate blocked production of N-13 ASP and N-13 ALA, and increased N-13 GLN slightly (6.0%). All studies had similar residual fractions (50%) except AOA treated septa (23%) indicating decreased metabolic trapping of the N-13 label. In conclusion, nitrogen-13 distribution in tissue is primarily governed by glutamate interaction with transaminases. Although the Michaelis constants of glutamate for GOT (Km = 4 nM, pig heart), GPT (Km = 8.1 mM, beef heart) and glutamine synthetase (Km = 2.5 mM, ovine brain) are similar, the transaminases play a predominant role because of their great abundance in myocardial tissue.
Research Organization:
UCLA School of Medicine, Los Angeles, CA
OSTI ID:
6845471
Report Number(s):
CONF-840619-
Conference Information:
Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
Country of Publication:
United States
Language:
English