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Journal ArticleDOI

Does intracellular metabolite diffusion limit post-contractile recovery in burst locomotor muscle?

15 Jul 2005-The Journal of Experimental Biology (J Exp Biol)-Vol. 208, Iss: 14, pp 2641-2652

TL;DR: It is concluded that fiber SA:V and O2 flux exert more control than intracellular metabolite diffusive flux over the developmental changes in metabolic organization and metabolic fluxes that characterize these muscles.

AbstractPost-metamorphic growth in the blue crab entails an increase in body mass that spans several orders of magnitude. The muscles that power burst swimming in these animals grow hypertrophically, such that small crabs have fiber diameters that are typical of most cells ( 600·µm). Thus, as the animals grow, their muscle fibers cross and greatly exceed the surface area to volume ratio (SA:V) and intracellular diffusion distance threshold that is adhered to by most cells. Large fiber size should not impact burst contractile function, but post-contractile recovery may be limited by low SA:V and excessive intracellular diffusion distances. A number of changes occur in muscle structure, metabolic organization and metabolic flux during development to compensate for the effects of increasing fiber size. In the present study, we examined the impact of intracellular metabolite diffusive flux on the rate of postcontractile arginine phosphate (AP) resynthesis in burst locomotor muscle from small and large animals. AP recovery was measured following burst exercise, and these data were compared to a mathematical reaction‐diffusion model of aerobic metabolism. The measured rates of AP resynthesis were independent of fiber size, while simulations of aerobic AP resynthesis yielded lower rates in large fibers. These contradictory findings are consistent with previous observations that there is an increased reliance on anaerobic metabolism for post-contractile metabolic recovery in large fibers. However, the model results suggest that the interaction between mitochondrial ATP production rates, ATP consumption rates and diffusion distances yield a system that is not particularly close to being limited by intracellular metabolite diffusion. We conclude that fiber SA:V and O2 flux exert more control than intracellular metabolite diffusive flux over the developmental changes in metabolic organization and metabolic fluxes that characterize these muscles.

Topics: Phosphagen (51%), Anaerobic exercise (50%)

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Citations
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Journal ArticleDOI
TL;DR: Water can generate small active clusters and macroscopic assemblies, which can both transmit information on different scales and allow water to execute an intricate three-dimensional 'ballet' while retaining complex order and enduring effects.
Abstract: Liquid water is a highly versatile material. Although it is formed from the tiniest of molecules, it can shape and control biomolecules. The hydrogen-bonding properties of water are crucial to this versatility, as they allow water to execute an intricate three-dimensional 'ballet', exchanging partners while retaining complex order and enduring effects. Water can generate small active clusters and macroscopic assemblies, which can both transmit information on different scales.

516 citations


Journal ArticleDOI
TL;DR: Experimental measurements of metabolic fluxes, diffusion distances and diffusion coefficients, coupled with reaction–diffusion mathematical models in a range of muscle types has started to reveal some general principles guiding muscle structure and metabolic function.
Abstract: Metabolic processes are often represented as a group of metabolites that interact through enzymatic reactions, thus forming a network of linked biochemical pathways. Implicit in this view is that diffusion of metabolites to and from enzymes is very fast compared with reaction rates, and metabolic fluxes are therefore almost exclusively dictated by catalytic properties. However, diffusion may exert greater control over the rates of reactions through: (1) an increase in reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the relevant diffusion coefficients. It is therefore not surprising that skeletal muscle fibers have long been the focus of reaction–diffusion analyses because they have high and variable rates of ATP turnover, long diffusion distances, and hindered metabolite diffusion due to an abundance of intracellular barriers. Examination of the diversity of skeletal muscle fiber designs found in animals provides insights into the role that diffusion plays in governing both rates of metabolic fluxes and cellular organization. Experimental measurements of metabolic fluxes, diffusion distances and diffusion coefficients, coupled with reaction–diffusion mathematical models in a range of muscle types has started to reveal some general principles guiding muscle structure and metabolic function. Foremost among these is that metabolic processes in muscles do, in fact, appear to be largely reaction controlled and are not greatly limited by diffusion. However, the influence of diffusion is apparent in patterns of fiber growth and metabolic organization that appear to result from selective pressure to maintain reaction control of metabolism in muscle.

62 citations


Cites background from "Does intracellular metabolite diffu..."

  • ...…density (Kinsey et al., 2007; Locke and Kinsey, 2008), from respiration rates of isolated mitochondria (Burpee et al., 2010), or from direct measurements of ATP turnover using NMR in isolated muscles or in vivo (Kinsey et al., 2005; Hardy et al., 2006; Nyack et al., 2007; Jimenez et al., 2008)....

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  • ...This allows phosphagen resynthesis to occur faster than our reaction–diffusion model predicted that it should in the large fibers (Kinsey et al., 2005)....

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  • ...THE JOURNAL OF EXPERIMENTAL BIOLOGY 264 can be <0.1mol ATPg–1min–1 (Kinsey et al., 2005; Nyack et al., 2007), whereas in insect flight muscle it can exceed 2000mol ATPg–1min–1 (Suarez, 1998)....

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Journal ArticleDOI
TL;DR: Biological and ecological data of marine and freshwater fishes from the southern Neotropics, including Patagonia, are reviewed, and several examples of dependence on temperature are reported, from glacial times to today’s climate change.
Abstract: The latitudinal extension of southern South America imposes a thermal gradient that affects the structure of marine and freshwater fish assemblages and the biology of the species through direct exposure to the temperature gradients or by means of a web of historical and ecological relationships. We have reviewed biological and ecological data of marine and freshwater fishes from the southern Neotropics, including Patagonia, and report several examples of dependence on temperature, from glacial times to today’s climate change. We were able to identify historic and present effects on the diversity of fish assemblages, isolation, southern limits for the distribution of species, and morphological variation among populations. There is a wide range of characteristics that exemplify an adaptation to low temperatures, including biochemical peculiarities, physiological adjustments, and alternative life history patterns, and these appear in both freshwater and marine, and native and exotic fishes. The consequences of stable temperature regimes in both the ocean and thermal streams deserve special mention as these shape specialists under conditions of low selective pressure. At present, habitat use and interactions among species are being subject to changes as consequences of water temperature, and some of these are already evident in the northern and southern hemispheres.

57 citations


Cites methods from "Does intracellular metabolite diffu..."

  • ...This idea, called the ‘optimal fiber size hypothesis’, was proposed by Johnston et al. (2003, 2004) for notothenioids and Arctic char evolution and by Kinsey et al. (2005) for blue crabs....

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Journal ArticleDOI
Abstract: A fundamental principle of physiology is that cells are small in order to minimize diffusion distances for O(2) and intracellular metabolites. In skeletal muscle, it has long been recognized that aerobic fibers that are used for steady state locomotion tend to be smaller than anaerobic fibers that are used for burst movements. This tendency reflects the interaction between diffusion distances and aerobic ATP turnover rates, since maximal intracellular diffusion distances are ultimately limited by fiber size. The effect of diffusion distance on O(2) flux in muscle has been the subject of quantitative analyses for a century, but the influence of ATP diffusion from mitochondria to cellular ATPases on aerobic metabolism has received much less attention. The application of reaction-diffusion mathematical models to experimental measurements of aerobic metabolic processes has revealed that the extreme diffusion distances between mitochondria found in some muscle fibers do not necessarily limit the rates of aerobic processes per se, as long as the metabolic process is sufficiently slow. However, skeletal muscle fibers from a variety of animals appear to have intracellular diffusion distances and/or fiber sizes that put them on the brink of diffusion limitation. Thus, intracellular metabolite diffusion likely influences the evolution of muscle design and places limits on muscle function.

54 citations


Cites background or methods from "Does intracellular metabolite diffu..."

  • ...Coupling experimental data with a reaction–diffusion mathematical model, however, we found that the observed rate of AP resynthesis following burst contraction in the anaerobic locomotor fibers of small and large blue crabs was not dramatically limited by intracellular metabolite diffusion (Kinsey et al., 2005)....

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  • ...…data with a reaction–diffusion mathematical model, however, we found that the observed rate of AP resynthesis following burst contraction in the anaerobic locomotor fibers of small and large blue crabs was not dramatically limited by intracellular metabolite diffusion (Kinsey et al., 2005)....

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  • ...…during fiber growth can be demonstrated by rearranging the equation described above for displacement, , to solve for diffusion time, t, using time-dependent diffusion coefficients and mitochondrial spacing data from a crustacean muscle example (Kinsey and Moerland, 2002; Kinsey et al., 2005)....

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  • ...Quantitative analyses of some skeletal muscle types indicate that the extent to which metabolite diffusion limits aerobic flux is variable (e.g. Mainwood and Rakusan, 1982; Meyer et al., 1984; Tyler and Sidell, 1984; Egginton and Sidell, 1989; Hubley et al., 1997; Kemp et al., 1998; Kinsey et al., 2005; Hardy et al., 2006; Nyack et al., 2007), but a broad analysis that encompasses diffusion effects over the full spectrum of muscle fiber designs is lacking....

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  • ...…variable (e.g. Mainwood and Rakusan, 1982; Meyer et al., 1984; Tyler and Sidell, 1984; Egginton and Sidell, 1989; Hubley et al., 1997; Kemp et al., 1998; Kinsey et al., 2005; Hardy et al., 2006; Nyack et al., 2007), but a broad analysis that encompasses diffusion effects over the full spectrum of…...

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Journal ArticleDOI
TL;DR: Reaction-diffusion mathematical models demonstrate that diffusion would greatly constrain the rate of metabolic processes without these developmental changes in fiber structure.
Abstract: Muscle fibers that power swimming in the blue crab Callinectes sapidus are <80 μm in diameter in juveniles but grow hypertrophically, exceeding 600 μm in adults. Therefore, intracellular diffusion distances become progressively greater as the animals grow and, in adults, vastly exceed those in most cells. This developmental trajectory makes C. sapidus an excellent model for characterization of the influence of diffusion on fiber structure. The anaerobic light fibers, which power burst swimming, undergo a prominent shift in organelle distribution with growth. Mitochondria, which require O2 and rely on the transport of small, rapidly diffusing metabolites, are evenly distributed throughout the small fibers of juveniles, but in the large fibers of adults they are located almost exclusively at the fiber periphery where O2 concentrations are high. Nuclei, which do not require O2, but rely on the transport of large, slow-moving macromolecules, have the inverse pattern: they are distributed peripherally in small fibers but are evenly distributed across the large fibers, thereby reducing diffusion path lengths for large macromolecules. The aerobic dark fibers, which power endurance swimming, have evolved an intricate network of cytoplasmically isolated, highly perfused subdivisions that create the short diffusion distances needed to meet the high aerobic ATP turnover demands of sustained contraction. However, fiber innervation patterns are the same in the dark and light fibers. Thus the dark fibers appear to have disparate functional units for metabolism (fiber subdivision) and contraction (entire fiber). Reaction-diffusion mathematical models demonstrate that diffusion would greatly constrain the rate of metabolic processes without these developmental changes in fiber structure.

38 citations


Cites background or methods or result from "Does intracellular metabolite diffu..."

  • ...This argument is supported by reaction-diffusion model analyses of experimental data, which indicated that the low rate of postcontractile phosphocreatine or arginine phosphate recovery in large anaerobic fibers is not substantially limited by diffusion, despite the presence of extremely large diffusion distances (29, 38, 49)....

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  • ...Anaerobic fibers may therefore tolerate comparatively long intracellular diffusion distances (38), which is consistent with the observation that anaerobic fibers tend to be larger than aerobic fibers....

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  • ...This is consistent with our previous finding that postcontractile phosphagen recovery is not substantially limited by metabolite diffusion in the anaerobic light fibers (38)....

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  • ...Using previously measured maximal rates of aerobic metabolism in the light fibers (38), we found that the small, light fibers [with diffusive length scale (L) 40 m] had a high when we assumed that 48% of the ATP production was via SS mitochondria (observed case) and when we assumed that all ATP production was via the IM mitochondria (no SS mitochondria; Table 1)....

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  • ...Crabs were induced to undergo a burst swimming response, as described previously (6, 24, 30, 38)....

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References
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Book
01 Jan 1984
Abstract: This book is about the importance of animal size. We tend to think of animal function in chemical terms and talk of water, salts, proteins, enzymes, oxygen, energy, and so on. We should not forget, however, that physical laws are equally important, for they determine rates of diffusion and heat transfer, transfer of force and momentum, the strength of structures, the dynamics of locomotion, and other aspects of the functioning of animal bodies. Physical laws provide possibilities and opportunities for an organism, yet they also impose constraints, setting limits to what is physically possible. This book aims to give an understanding of these rules because of their profound implications when we deal with animals of widely different size and scale. The reader will find that the book raises many questions. Remarkable and puzzling information makes it read a little like a detective story, but the last chapter, instead of giving the final solution, neither answers all questions nor provides one great unifying principle.

2,736 citations


Journal ArticleDOI

1,851 citations


"Does intracellular metabolite diffu..." refers background in this paper

  • ...The intracellular diffusive flux of high-energy phosphates is largely mediated by phosphagen kinases, such as creatine kinase (CK) and arginine kinase (AK), although the mechanistic details are still the subject of study (reviewed by Walliman et al., 1992; Ellington, 2001)....

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Journal ArticleDOI
TL;DR: Phosphocreatine content was measured by phosphorus nuclear magnetic resonance spectroscopy in the gastrocnemius muscles of pentobarbital-anesthetized rats during and after twitch stimulation to be consistent with a simple first-order electrical analog model of oxidative metabolism that is applicable at submaximal oxidative rates.
Abstract: Phosphocreatine (PCr) content was measured by phosphorus nuclear magnetic resonance spectroscopy in the gastrocnemius muscles of pentobarbital-anesthetized rats during and after twitch stimulation at rates up to 0.75 Hz. The monoexponential time constant for PCr changes was similar at the onset of vs. during recovery after stimulation and was not significantly different for different stimulation rates (mean time constant 1.44 min). Steady-state PCr level during stimulation was linearly related to the product of stimulation rate times peak twitch force. These results are shown to be consistent with a simple first-order electrical analog model of oxidative metabolism that is applicable at submaximal oxidative rates. The model assumes equilibrium of the creatine kinase reaction, which is modeled as a chemical capacitor, with capacitance proportional to the total creatine level, and PCr level proportional to the cytosolic free energy of ATP hydrolysis.

491 citations


"Does intracellular metabolite diffu..." refers methods in this paper

  • ...This approach has been effectively employed to describe some of the major processes of energy metabolism in muscle, and a variety of kinetic models have been developed that closely match experimental data (e.g. Meyer, 1988; Jeneson et al., 1995; Vicini and Kushmerick, 2000; Korzeniewski, 2003)....

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Journal ArticleDOI
TL;DR: Experimental results demonstrating the transport aspects of the CK reaction emphasize only one feature of a more general notion of facilitated diffusion by near-equilibrium metabolic reactions and do not per se establish the existence of any physical or functional compartmentation of ATP, ADP, PCr, or creatine.
Abstract: The diffusive mobility of solutes chemically connected by reversible reactions in cells is analyzed as a problem of facilitated diffusion. By this term we mean that the diffusive flux of any substance, X, which is in one metabolic pathway, is effectively increased when it participates in a second and equilibrium reaction with another substance Y because the total flux of X in the pathway is the sum of the fluxes of X and Y. This notion is generalized and is seen to include the familiar enhanced intracellular diffusion of oxygen by oxymyoglobin. In this framework the function of creatine kinase (CK) is seen to have two aspects: 1) phosphocreatine (PCr) via the CK reaction buffers the cellular ATP and ADP concentrations and 2) transport of high-energy phosphates is predominantly in the chemical form of PCr. This predominance of PCr is a consequence of the maintained ATP, ADP, and total creatine levels and of the apparent equilibrium constant of the reaction. Thus experimental results demonstrating the transport aspects of the CK reaction emphasize only one feature of a more general notion of facilitated diffusion by near-equilibrium metabolic reactions and do not per se establish the existence of any physical or functional compartmentation of ATP, ADP, PCr, or creatine. PCr can be a large source for increasing inorganic phosphate levels during contractile activity, possibly as a metabolic regulator. Neither the transport nor buffer aspects can be quantitatively important in cells with small distances between ATP-utilizing and ATP-generating sites, such as is the case with cardiac myofibrils and mitochondria.

481 citations


"Does intracellular metabolite diffu..." refers background or methods in this paper

  • ...These are likely to include systems with relatively high rates of ATP production/consumption and distant sites of ATP utilization, such as in some muscle fibers with a higher aerobic capacity than examined here (Meyer et al., 1984; Stokes and Josephson, 1992; Vendelin et al., 2000; Saks et al., 2003; Suarez, 2003) or in the flagellum of spermatozoa, which has been the subject of many reaction–diffusion analyses (e....

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  • ...…metabolism found theoretical evidence for concentration gradients in high-energy phosphate molecules during steady-state contraction in muscle (Mainwood and Rakusan, 1982; Meyer et al., 1984; Hubley et al., 1997; Aliev and Saks, 1997; Kemp et al., 1998; Vendelin et al., 2000; Saks et al., 2003)....

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  • ...The mitochondrial boundary conditions at x=0 balance the fluxes of ATP and ADP into the bulk phase with the rates of formation and consumption at the mitochondria and are modeled using Michaelis-Menten kinetics with ADP activation (Meyer et al., 1984):...

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  • ...A Km,mito value for ADP of 20·µmol·l–1 was used, which is within the range for fast skeletal muscle (Meyer et al., 1984)....

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  • ...…the bulk phase with the rates of formation and consumption at the mitochondria and are modeled using Michaelis-Menten kinetics with ADP activation (Meyer et al., 1984): where RmitoATP and RmitoADP are the boundary reaction rates for ATP and ADP, respectively, Vm,mito is the maximal velocity…...

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Journal ArticleDOI
TL;DR: It is hypothesized that the capacity for intracellular targeting of CK evolved early as a means of facilitating energy transport in highly polarized cells and was subsequently exploited for temporal ATP buffering and dynamic roles in metabolic regulation in cells displaying high and variable rates of aerobic energy production.
Abstract: Phosphagens are phosphorylated guanidino compounds that are linked to energy state and ATP hydrolysis by corresponding phosphagen kinase reactions: phosphagen + MgADP + H(+) guanidine acceptor + MgATP. Eight different phosphagens (and corresponding phosphagen kinases) are found in the animal kingdom distributed along distinct phylogenetic lines. By far, the creatine phosphate/creatine kinase (CP/CK) system, which is found in the vertebrates and is widely distributed throughout the lower chordates and invertebrates, is the most extensively studied phosphagen system. Phosphagen kinase reactions function in temporal ATP buffering, in regulating inorganic phosphate (Pi) levels, which impacts glycogenolysis and proton buffering, and in intracellular energy transport. Phosphagen kinase reactions show differences in thermodynamic poise, and the phosphagens themselves differ in terms of certain physical properties including intrinsic diffusivity. This review evaluates the distribution of phosphagen systems and tissue-specific expression of certain phosphagens in an evolutionary and functional context. The role of phosphagens in regulation of intracellular Pi levels likely evolved early. Thermodynamic poise of the phosphagen kinase reaction profoundly impacts this capacity. Furthermore, it is hypothesized that the capacity for intracellular targeting of CK evolved early as a means of facilitating energy transport in highly polarized cells and was subsequently exploited for temporal ATP buffering and dynamic roles in metabolic regulation in cells displaying high and variable rates of aerobic energy production.

451 citations


"Does intracellular metabolite diffu..." refers background in this paper

  • ...The intracellular diffusive flux of high-energy phosphates is largely mediated by phosphagen kinases, such as creatine kinase (CK) and arginine kinase (AK), although the mechanistic details are still the subject of study (reviewed by Walliman et al., 1992; Ellington, 2001)....

    [...]