Studies of energy transport in heart cells. The importance of creatine kinase localization for the coupling of mitochondrial phosphorylcreatine production to oxidative phosphorylation.

Saks, Valdur; Kupriyanov, V.V.; Elizarova, Galina V.; Jacobus, William E.

doi:10.1016/s0021-9258(19)86245-2

Cited by 151 publications

(6 citation statements)

References 39 publications

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“…Given the similarity in kinetic properties of the isolated isoenzymes, simply substituting one isoenzyme for another would not be expected to alter the relationship between the rate of ATP synthesis and the creatine kinase reaction velocity. Instead, our results are consistent with experiments using isolated mitochondria in which the apparent Km of mito-CK for ATP was 5-fold lower when mito-CK was bound to the mitochondria than when it was unbound (Saks et al, 1980), demonstrating the importance of localization of this isoenzyme. Our results also show that as mito-CK activity increased increased despite no change in total creatine kinase activity.…”

Section: Discussionsupporting

confidence: 91%

Velocity of the creatine kinase reaction in the neonatal rabbit heart: role of mitochondrial creatine kinase

Perry

McAuliffe²,

Balschi³

et al. 1988

Biochemistry

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To examine the role of changes in the distribution of the creatine kinase (CK) isoenzymes [BB, MB, MM, and mitochondrial CK (mito-CK)] on the creatine kinase reaction velocity in the intact heart, we measured the creatine kinase reaction velocity and substrate concentrations in hearts from neonatal rabbits at different stages of development. Between 3 and 18 days postpartum, total creatine kinase activity did not change, but the isoenzyme distribution and total creatine content changed. Hearts containing 0, 4, or 9% mito-CK activity were studied at three levels of cardiac performance: KCl arrest and Langendorff and isovolumic beating. The creatine kinase reaction velocity in the direction of MgATP production was measured with 31P magnetization transfer under steady-state conditions. Substrate concentrations were measured with 31P NMR (ATP and creatine phosphate) and conventional biochemical analysis (creatine) or estimated (ADP) by assuming creatine kinase equilibrium. The rate of ATP synthesis by oxidative phosphorylation was estimated with oxygen consumption measurements. These results define three relationships. First, the creatine kinase reaction velocity increased as mito-CK activity increased, suggesting that isoenzyme localization can alter reaction velocity. Second, the reaction velocity increased as the rate of ATP synthesis increased. Third, as predicted by the rate equation, reaction velocity increased with the 3-fold increase in creatine and creatine phosphate contents that occurred during development.

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Section: Discussionsupporting

confidence: 91%

Velocity of the creatine kinase reaction in the neonatal rabbit heart: role of mitochondrial creatine kinase

Perry

McAuliffe²,

Balschi³

et al. 1988

Biochemistry

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“…When this is done, some results are consistent with near-equilibrium of CK, but others are not. In either case, these interpretations appear to be highly model-dependent, and this model ignores evidence from several laboratories which suggests strongly that the concentrations of ATP and ADP at the active sites of mitochondrial CK may be markedly different, perhaps 5-to 10-fold, from those in the cytoplasm (Saks et al ., 1976(Saks et al ., , 1980Yang et al, 1977 ;DeFuria et al, 1980 ;Erickson-Viitanen et al, 1982 a, b ;Moreadith and Jacobus, 1982). As discussed above, the concentrations of ATP and ADP at the active sites of the CK bound near ATPases may also be appreciably different from the average concentrations in the cytoplasm .…”

Section: Role Of Mitochondrial Creatine Kinase In the Control Of Respirationmentioning

confidence: 99%

“…However, discussion of the shuttle hypothesis by its proponents shows that a key element in it is the proposal that, outside the matrix, changes in [ATP] and [ADP] are largely restricted to microenvironments near the ATPases and translocase, because of the juxtaposition of bound CK. An important ancillary hypothesis is that changes in the rates at which ATP is delivered to the ATPases, and ADP to the translocase, are triggered by changes in cytoplasmic [PC] and [creatine] (Gercken and Schlette, 1968;Saks et al, 1974Saks et al, , 1976Saks et al, , 1978Saks et al, , 1980Jacobus, 1980;Bessman and Geiger, 1981 ;Moreadith and Jacobus, 1982;Jacobus and Diffley, 1983). In this context, it is clear that no model postulating a well-stirred cytoplasm can be consistent with the creatine shuttle hypothesis.…”

Section: Role Of Mitochondrial Creatine Kinase In the Control Of Respirationmentioning

confidence: 99%

First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and phosphorylcreatine level. Implications for the control of respiration.

Mahler¹

1985

The Journal of General Physiology

210

152

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In frog sartorius muscle, after a tetanus at 20°C, during which an impulse-like increase occurs in the rate of ATP hydrolysis, the rate of 02 consumption (Qo,) reaches a peak relatively quickly and then declines monoexponentially, with a time constant not dependent on the tetanus duration (T = 2 .6 min in Rana pipiens and 2 .1 min in Rana temporaria). To a good approximation, these kinetics are those of a first-order impulse response, and the scheme of reactions that couple 02 consumption to extramitochondrial ATP hydrolysis thus behaves as a first-order system . It is first deduced and then demonstrated directly that while Qo,(t) is monoexponential, it changes in parallel with the levels of creatine and phosphorylcreatine, with proportionality constants ±1/Tp, where p is the P/02 ratio in vivo . From this, it is further deduced that the mitochondrial creatine kinase (CK) reaction is pseudo-first order in vivo . The relationship between [creatine] and Qo, predicted by published models of the control of respiration is markedly different from that actually observed . As shown here, the first-order kinetics of Qo, are consistent with the hypothesis that respiration is rate-limited by the mitochondrial CK reaction ; this has as a corollary the "creatine shuttle" hypothesis .

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“…The potential regulatory role of this system in cardiac muscle contraction is based on the assumed phenomenon of compartmentation of adenine nucleotides inside highly organized and differentiated muscle cells (for a recent review, see Walliman and Eppenberger, 1985 ;Bessman and Carpenter, 1985). In mitochondria, the creatine kinase isoenzyme is coupled to oxidative phosphorylation and participates in the compartmentation of adenine nucleotides in these structures (Jacobus and Lehninger, 1973 ;Saks et al, 1980;Jacobus et al, 1982;Moreadith and Jacobus, 1982 ;Gellerich and Saks, 1982). The MM-creatine kinase isoenzyme of muscle myofibrils plays an important role in supplying energy for contraction in heart muscle (Saks et al ., 1976); this enzyme is functionally coupled to myofibrillar ATPase (Bessman et al ., 1980;Walliman et al, 1984 ;Saks et al ., 1984).…”

Section: Introductionmentioning

confidence: 99%

Role of creatine kinase in force development in chemically skinned rat cardiac muscle.

Ventura‐Clapier¹,

Mekhfi²,

Vassort³

1987

The Journal of General Physiology

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The influence of phosphocreatine in the presence or absence of MgATP and MgADP was studied in Triton X-100-treated thin papillary muscles and ventricular strips of the rat heart. The pCa/tension relationships, the pMgATP/tension relationships, and the tension responses to quick length changes were analyzed. The results show three major consequences of the reduction of the phosphocreatine concentration in the presence of millimolar concentrations of the MgATP. (a) The resting tension and the maximal Ca"-activated tension were increased, and the pCa/tension relationship was shifted toward higher pCa values and its steepness was decreased ; these effects were enhanced by the inclusion of MgADP. (b) The time constant of tension recoveries after quick stretches applied during maximal activation was increased, while the extent of these recoveries was decreased . (c) The study of pMgATP/ tension relationships in low Ca concentrations showed that the decrease in phosphocreatine induced a shift toward higher MgATP values with no changes in maximal rigor tension or the slope coefficient; these effects were increased by the increase in MgADP and were independent of the preparation diameter. Thus, modifications of the apparent Ca sensitivity and resting and maximal tension when phosphocreatine is decreased seem to be due to an increasing participation of rigor-like or slowly cycling cross-bridges spending more time in the attached state. These results suggest that endogenous creatine kinase is able to ensure maximal efficiency of myosin ATPase by producing a local high MgATP/MgADP ratio.

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Studies of energy transport in heart cells. The importance of creatine kinase localization for the coupling of mitochondrial phosphorylcreatine production to oxidative phosphorylation.

Cited by 151 publications

References 39 publications

Velocity of the creatine kinase reaction in the neonatal rabbit heart: role of mitochondrial creatine kinase

Velocity of the creatine kinase reaction in the neonatal rabbit heart: role of mitochondrial creatine kinase

First-order kinetics of muscle oxygen consumption, and an equivalent proportionality between QO2 and phosphorylcreatine level. Implications for the control of respiration.

Role of creatine kinase in force development in chemically skinned rat cardiac muscle.

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