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The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle.

Cooke R - Biophys Rev (2011)

Bottom Line: Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle.In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding.Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry & Biophysics, Cardiovascular Research Institute, University of California, Box 2240, Genentech Hall, 600, 6th Street, San Francisco, CA 94158-2517 USA.

ABSTRACT
Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the "furnace" that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430-435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

No MeSH data available.


Related in: MedlinePlus

Fluorescence intensities are shown as a function of time during a chase with a relaxing solution (open circles, red) or with an activating solution (closed squares, blue). In the relaxing solution, there is a slow release of nucleotides from the SRX, while in the activating solution all nucleotides are released in the rapid phase. The fibers were initially relaxed in 250 uM mantATP. The chase solution was either a relaxing solution, containing 4 mM ATP, pCa approx. 9, or an activating solution containing 4 mM ATP and calcium, pCa = 5.7. The fibers in the activating solution generated 60% of maximal tension
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Fig4: Fluorescence intensities are shown as a function of time during a chase with a relaxing solution (open circles, red) or with an activating solution (closed squares, blue). In the relaxing solution, there is a slow release of nucleotides from the SRX, while in the activating solution all nucleotides are released in the rapid phase. The fibers were initially relaxed in 250 uM mantATP. The chase solution was either a relaxing solution, containing 4 mM ATP, pCa approx. 9, or an activating solution containing 4 mM ATP and calcium, pCa = 5.7. The fibers in the activating solution generated 60% of maximal tension

Mentions: The three-state model proposed for myosin with approximate nucleotide turnover times. In active muscle, myosin heads are primarily in the active state with rapid nucleotide turnover. In relaxed muscle, myosin can be in one of two states: (1) the normally relaxed state, with a turnover time approximately equal to that of purified myosin, which is 6 s for rabbit myosin at in vivo temperature or (2) the super relaxed state (SRX), with a much slower turnover time, 230 s. Two factors have been shown to alter rates between the relaxed state and the SRX. Myosin heads in active cycles increase the rate from the SRX to the relaxed state (Fig. 4). Phosphorylation (∼P) of the regulatory light chain (RLC) also favors the relaxed state, although it is not known whether this is due to increased rates from the SRX to the relaxed state, or to a decreased rate in the reverse direction


The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle.

Cooke R - Biophys Rev (2011)

Fluorescence intensities are shown as a function of time during a chase with a relaxing solution (open circles, red) or with an activating solution (closed squares, blue). In the relaxing solution, there is a slow release of nucleotides from the SRX, while in the activating solution all nucleotides are released in the rapid phase. The fibers were initially relaxed in 250 uM mantATP. The chase solution was either a relaxing solution, containing 4 mM ATP, pCa approx. 9, or an activating solution containing 4 mM ATP and calcium, pCa = 5.7. The fibers in the activating solution generated 60% of maximal tension
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3064898&req=5

Fig4: Fluorescence intensities are shown as a function of time during a chase with a relaxing solution (open circles, red) or with an activating solution (closed squares, blue). In the relaxing solution, there is a slow release of nucleotides from the SRX, while in the activating solution all nucleotides are released in the rapid phase. The fibers were initially relaxed in 250 uM mantATP. The chase solution was either a relaxing solution, containing 4 mM ATP, pCa approx. 9, or an activating solution containing 4 mM ATP and calcium, pCa = 5.7. The fibers in the activating solution generated 60% of maximal tension
Mentions: The three-state model proposed for myosin with approximate nucleotide turnover times. In active muscle, myosin heads are primarily in the active state with rapid nucleotide turnover. In relaxed muscle, myosin can be in one of two states: (1) the normally relaxed state, with a turnover time approximately equal to that of purified myosin, which is 6 s for rabbit myosin at in vivo temperature or (2) the super relaxed state (SRX), with a much slower turnover time, 230 s. Two factors have been shown to alter rates between the relaxed state and the SRX. Myosin heads in active cycles increase the rate from the SRX to the relaxed state (Fig. 4). Phosphorylation (∼P) of the regulatory light chain (RLC) also favors the relaxed state, although it is not known whether this is due to increased rates from the SRX to the relaxed state, or to a decreased rate in the reverse direction

Bottom Line: Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle.In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding.Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry & Biophysics, Cardiovascular Research Institute, University of California, Box 2240, Genentech Hall, 600, 6th Street, San Francisco, CA 94158-2517 USA.

ABSTRACT
Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the "furnace" that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430-435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels.

No MeSH data available.


Related in: MedlinePlus