Ra. Howlett et Wt. Willis, FIBER-TYPE-RELATED DIFFERENCES IN THE ENZYMES OF A PROPOSED SUBSTRATECYCLE, Biochimica et biophysica acta. Bioenergetics, 1363(3), 1998, pp. 224-230
A substrate cycle between citric acid cycle (CAC) intermediates isocit
rate and 2-oxoglutarate, involving NAD(+)- and NADP(+)-linked isocitra
te dehydrogenase (NAD-IDH and NADP-IDH, respectively) and mitochondria
l transhydrogenase (H+-Thase), has recently been proposed. This cycle
has been hypothesized to enhance mito-chondrial respiratory control by
increasing the sensitivity of NAD-IDH to its modulators and allowing
for enhanced increases in flux through this step of the CAC during per
iods of increased ATP demand. The activities of the enzymes comprising
the substrate cycle: NAD-IDH, forward and reverse NADP-IDH. and forwa
rd and reverse H+-Thase, along with the activity of a marker of mitoch
ondrial content, citrate synthase (CS) were measured in mitochondria i
solated from rabbit Type I and Type IIb muscles and in whole muscle ho
mogenates, representing the various fiber types, from rats. In isolate
d rabbit muscle mitochondria, NAD-IDH had significantly higher (1.6 X)
activity in white muscle while forward NADP-IDH, forward and reverse
H+-Thase. and CS all had significantly higher (1.3-1.6 X) activities i
n red muscle, There was no difference in reverse NADP-IDH between fibe
r types. Similarly, in rat whole muscle enzyme activities normalized t
o CS, NAD-IDH had significantly higher activity in fast-twitch glycoly
tic (FG) fibers, while forward NADP-IDH and forward H+-Thase had signi
ficantly higher activities in slow-twitch oxidative (SO) fibers. These
results suggest that differences in the activities of the substrate c
ycle enzymes between skeletal muscle fiber types could contribute to d
ifferences in respiratory control due to differential cycling rates an
d/or loci of control. (C) 1998 Elsevier Science B.V.