AJP - Heart and Circulatory Physiology, Vol 261, Issue 6 1919-H1926, Copyright © 1991 by American Physiological Society
Effect of cyclocreatine feeding on levels of amino acids in rat hearts before and after an ischemic episode
M. Osbakken, D. N. Zhang, D. Nelson and M. Erecinska
Department of Medicine (Cardiology), University of Pennsylvania School of Medicine, Philadelphia 19104.
Feeding Sprague-Dawley rats for 3 wk a diet containing 1% by weight of
cyclocreatine increased the reservoir of the high-energy phosphate
compounds but also caused alterations in the levels of the two key amino
acids, aspartate and glutamate. Both were decreased by approximately 50% in
the presence of an unaltered content of glutamine. In vitro exposure of
these hearts to sequential perfusion, global ischemia, and reperfusion in
the absence of added amino acids resulted in changes in aspartate,
glutamate, and glutamine that were different from those in hearts from
control rats. In the cyclocreatine-fed group, aspartate concentration
([aspartate]) and [glutamate] fell after global ischemia, whereas
[glutamine] was unaltered. [Glutamine] decreased, however, in the
reperfusion period. In control hearts, the predominant effect was a steady
decline in glutamine, which was accompanied by either less than 10% (after
global ischemia) or 30-50% fall (after reperfusion) in [aspartate] and
[glutamate]. The concentration of tissue Pi was smaller in hearts from
cyclocreatine-fed rats and appeared to increase more slowly during
ischemia. In the presence of rotenone and aminooxyacetate, heart
homogenates catalyzed production of glutamate from glutamine, which was
markedly stimulated by Pi and inhibited by H+. It is postulated that 1)
phosphate-activated glutaminase is an important enzyme that determines
cardiac [glutamate], 2) lower [phosphate] in hearts from rats fed
cyclocreatine is responsible for the apparently lesser activity of
glutaminase, 3) breakdown of the high-energy phosphate compounds and
consequent rise in Pi activates glutaminase, and 4) slow breakdown of
glutamine during global ischemia is a result of inhibition of glutaminase
by H+.
