Sn. Fedosov, CREATINE-CREATINE PHOSPHATE SHUTTLE MODELED AS 2-COMPARTMENT SYSTEM AT DIFFERENT LEVELS OF CREATINE-KINASE ACTIVITY, Biochimica et biophysica acta. Protein structure and molecular enzymology, 1208(2), 1994, pp. 238-246
In order to characterize ADP-ATP and creatine-creatine phosphate (Cr-C
rP) shuttles a minimal mathematical model with two compartments and cy
clic turnover of matter was designed. The 'mitochondrial' compartment
contained 'ATP-synthase' and 'mitochondrial creatine kinase' (mitCK).
The 'cytoplasmic' compartment consisted of 'ATPase', 'cytoplasmic crea
tine kinase' (cytCK) and an 'ADP-binding structure'. The exchange of m
etabolites between these compartments was limited. Different levels of
cytCK and mitCK expression as well as different exchange rate constan
ts between the compartments were assigned to obtain several different
modes. Every steady state obtained in the presence of low ATPase activ
ity ('resting' conditions) was then disturbed by a steep activation of
ATPase ('muscle performance') and afterwards the transition to a new
steady state was followed in time. The ATP-buffering capacity of the s
ystem initially acquired by cytCK expression significantly increased a
fter additional mitCK supplement. Nevertheless, even the complete Cr-C
rP shuttle failed to maintain a high [ATP]/[ADP] ratio during long ter
m 'muscle performance' due to the rate limiting CK-transphosphorylatio
n in the mitochondria. The facilitated diffusion of Cr and CrP was not
critical, and the model worked with the same efficiency even at equal
permeabilities for nucleotides and guanidines. Under 'resting conditi
ons' the main flux of matter went through the Cr-CrP shuttle, resultin
g in 'pumping' of CrP. This ensured a 40 s delay in the [ATP] decrease
at 'work'. The partial systems without mitCK were not as effective, a
nd this delay was 0-10 s. However, the ADP-ATP shuttle was of more imp
ortance at the steady state achieved under 'working' conditions.