Our bodies are constantly renewing themselves, discarding ageing tissues and replacing them with fresh ones. Without this turnover, our systems would fail, so turnover is a fundamental part of what we are.
The biochemistry of this is complex, however, and researchers are trying to learn what initiates and sustains this process. Dr William Reville, senior lecturer in biochemistry and director of electron microscopy at University College, Cork, is studying turnover in skeletal muscle.
Dr Reville was a member of the research team at Iowa University which first identified an enzyme, calpain, associated with this process. He has continued to study muscle turnover and currently has two postgraduate students involved in the work at UCC.
"We are studying protein turnover. Everything in the body is broken down and replaced, it is a basic function of life," he explained. Muscle makes up 40 per cent of all body weight and 70 per cent of the dry weight of muscle is protein.
Muscle cells are long cylindrical structures often extending the entire length of the muscle. Most of the protein content is given over to contraction and is organised into long fibre-like elements called myofibrils. These in turn are made up of many overlapping arrays of fine myofilaments.
Understanding these processes is about much more than satisfying scientific curiosity, Dr Reville said. "If we understand the mechanisms of turnover in normal muscle, we might be able to discover what takes place in diseased muscle," he said.
"It appears from research that many wasting muscle diseases such as Duchenne muscular dystrophy involve disorders in protein turnover, where breakdown greatly exceeds synthesis, leading to wasting."
Duchenne MD is invariably fatal and is the second-most common human genetic disease, so progress in this area could have a major impact.
Dr Reville's work focuses on the myofibrils and their interaction with the calpain enzyme which breaks them down. Expression of calpain has been shown to be increased in patients with muscle wasting diseases.
This is only a first step, however. His research has shown that the myofilaments at the surface of the myofibril are only loosely connected, and this is necessary to achieve flexibility. They are so loose that shaking can dislodge 5 per cent of surface myofilaments and exposure to calpain takes off up to 50 per cent of these "easily releasable myofilaments" (ERMs).
Research suggests that ERMs play a special role in turning over the myofibril protein, Dr Reville said. Early theories suggest that myofilaments deep inside the myofibril gradually migrate towards the surface as they age and in turn are discarded. Calpain mediates this removal of surface myofilaments.
His research group can "watch" what happens during this breakdown through use of UCC's electron microscope. "We need to be able to see the filaments coming off and we can only do that using an electron microscope. The electron microscope has been a central part of the research."
Dr Reville's research is also relevant to agriculture and meat production. The Department of Agriculture, Forestry and Food has funded his work for some years, recognising its potential value.
Meat production is about delivering maximum muscle mass at the lowest possible cost and so is inextricably linked to the turnover process, he said. The object is to try to speed up synthesis or to slow breakdown to increase mass. From his research he believes the "more productive line of attack" involves slowing breakdown rather than accelerating synthesis.
The work also applies to beef's tenderness. Freshly killed beef is tender but soon rigor mortis sets in and it becomes tough. It must hang in a cooler for at least two weeks to become tender again, a process brought about by the same protein breakdown system.
"We are interested in the mechanism whereby the meat goes tender again over that period," he said. It is driven by an enzyme reaction and the idea would be to speed up the process.