Metabolic compartmentation of lactate in the glucose perfused rat
heart.
Chatham, John C., and John R. Forder.
Division of NMR Research, Department of Radiology, The Johns
Hopkins University School of Medicine, Baltimore, MD, USA
APStracts 2:0315H, 1995.
Several studies using exogenous pyruvate as substrate have suggested
that there are separate intracellular pyruvate pools in cardiac
cells. Such heterogeneity in intracellular pyruvate has important
implications for our understanding of both oxidative and non
-oxidative glucose metabolism. Since pyruvate is not a major substrate
for the heart in vivo we wished to determine if there was pyruvate
compartmentation with glucose as substrate. Hearts were isolated from
male Sprague Dawley rats and retrogradely perfused (Langendorff) with
a modified Krebs-Henseleit buffer containing [1-13C]glucose for 20
-115 minutes. At the end of each experiment, hearts were freeze
-clamped and extracted for determination of the fractional enrichment
of alanine, lactate and acetyl-CoA using 1H and 13C NMR spectroscopy.
The fractional enrichment of alanine at the C3 position was
significantly higher than that for lactate at 55 minutes (43.6+/-2.8%
vs. 27.2+/-4.6%; n=5; mean+/-SD; p<0.003). The differences in
steady-state enrichment between lactate and alanine were not due to
differences in the rate of labeling of these metabolites. The mean
steady state lactate enrichment was higher in the perfusate samples
compared to the tissue samples from the same experiments (46.6+/-2.2%
vs. 30.5+/-2.5%; n=3; p<0.005). Since fractional enrichment at
alanine, acetyl-CoA and perfusate lactate are similar we suggest that
there is a separate non-exchanging pool of lactate rather than
cytosolic compartmentation of pyruvate that has been previously
proposed.
Received 3 March 1995; accepted in final form 10 July 1995.
APS Manuscript Number H204-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.