The role of the super-relaxed state of myosin in human metabolism.

Background: The super-relaxed state of myosin (SRX) plays a fundamental role in maintaining the low resting metabolic rate of skeletal muscle. Our previous work on this state has been in animal models. Piperine is a small molecule that has been shown to destabilize the SRX in rabbit fast twitch fibers.

Piperine, an alkaloid inhibiting the super-relaxed state of myosin, binds to the myosin regulatory light chain.

Piperine, an alkaloid from black pepper, was found to inhibit the super-relaxed state (SRX) of myosin in fast-twitch skeletal muscle fibers. In this work we report that the piperine molecule binds heavy meromyosin (HMM), whereas it does not interact with the regulatory light chain (RLC)-free subfragment-1 (S1) or with control proteins from the same muscle molecular machinery, G-actin and tropomyosin. To further narrow down the location of piperine binding, we studied interactions between piperine and a fragment of skeletal myosin consisting of the full-length RLC and a fragment of the heavy chain (HCF).

What do we know about sibling attended birth? An integrative literature review.

Objective: to consolidate existing research in the field of sibling attended birth (SAB) into a body of knowledge to inform decision-making processes and guide midwifery practice throughout the sibling attended birth experience.

Design: An integrative literature review.

Data Sources: CINAHL Complete, Cochrane Library, PubMed, Index New Zealand, Australia/New Zealand Reference Centre, grey literature databases REVIEW METHODS: An extensive search of five electronic databases as well as 17 grey literature databases was conducted.

Piperine's mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle.

We identify a target for treating obesity and type 2 diabetes, the consumption of calories by an increase in the metabolic rate of resting skeletal muscle. The metabolic rate of skeletal muscle can be increased by shifting myosin heads from the super-relaxed state (SRX), with a low ATPase activity, to a disordered relaxed state (DRX), with a higher ATPase activity. The shift of myosin heads was detected by a change in fluorescent intensity of a probe attached to the myosin regulatory light chain in skinned skeletal fibers, allowing us to perform a high-throughput screen of 2,128 compounds.

Spectroscopic Studies of the Super Relaxed State of Skeletal Muscle.

In the super-relaxed state of myosin, ATPase activity is strongly inhibited by binding of the myosin heads to the core of the thick filament in a structure known as the interacting-heads motif. In the disordered relaxed state myosin heads are not bound to the core of the thick filament and have an ATPase rate that is 10 fold greater. In the interacting-heads motif the two regulatory light chains appear to bind to each other.