Research from Everest: Can leucine help burn fat and spare muscle tissue during exercise?

Research on Mt. Everest climbers is adding to the evidence that an amino acid called leucine — found in foods, dietary supplements, energy bars and other products — may help people burn fat during periods of food restriction, such as climbing at high altitude, while keeping their muscle tissue. It was one of two studies reported here today at the 242nd National Meeting & Exposition of the American Chemical Society (ACS) on the elite corps of men and women who have tackled the highest peak on Earth, mountaineering’s greatest challenge.

In a pilot study of the feasibility of supplementing the diet of climbers with the branch chain amino acid, leucine, scientists studied 10 climbers for 6-8 weeks as they ascended Mt. Everest, which towers 29,000 feet above sea level. Since Sir Edmund Hillary and Sherpa guide Tenzing Norgay made the first successful climb in 1953, over 2,500 people have scaled Mt. Everest in the Himalayas. Thousands more tried and failed, with more than 216 deaths. The researchers were studying the physiological benefits of adding leucine to the climbers’ diets to help them stay healthy. The researchers are from the University of Utah.

Wayne Askew, Ph.D., and his co-investigator, Stacie Wing-Gaia, Ph.D., who headed the leucine study, explained that the extreme weather conditions, low oxygen levels, treacherous terrain and strenuous exercise during such climbs create a huge nutritional challenge. Weight loss at high altitude is exactly the opposite problem that is on the minds of millions of people in the United States and other countries who are trying to shed excess weight. Climbers often cannot or do not eat enough calories, failing to replenish their bodies with important nutrients. They lose both fat and muscle during an arduous climb, endangering their strength and motor coordination. At high altitudes, fat and muscle loss occurs not only when they are climbing, but also at rest.

“The significant part about this weight loss is that a disproportionate amount comes from the muscle mass,” said Askew. “This can be a problem on long expeditions at high altitude because the longer climbers are there and the higher they go, the weaker they get. The body breaks down the muscle for energy, so climbers don’t have it available for moving up the mountain.

“We knew that leucine has been shown to help people on very low-calorie, or so-called ‘calorie-restricted diets’, stay healthy at sea level,” said Askew. “It’s one of the components, the building blocks, of protein. But no one had tested whether leucine would help people stay healthy and strong at high altitudes, so we added leucine to specially prepared food bars that we gave to the climbers.”

Askew didn’t climb Mt. Everest, but members of his research team, Dr. Wing-Gaia and Dr. Rodway, went to base camp and measured expedition members’ fat and muscle by using an ultrasound device placed on the skin. They are currently examining the data to see whether climbers who ate the leucine bar retained more muscle than those who ate a bar without leucine. One finding that was apparent early on in the study was that the food item in which the leucine was delivered was critically important. The Everest climbers had difficulties consuming the three food bars per day that contained the additional leucine. Askew stressed that this was a small pilot study to test the feasibility of leucine supplementation at altitude, so definitive conclusions of its benefits at altitude await the results of a more controlled clinical study. The researchers plan to improve the palatability of the leucine food vehicle in consultation with military food product developers at Natick Research Development and Engineering Center and conduct a more controlled study at high altitude, possibly with the U.S. Army Institute of Environmental Medicine at their laboratory on Pike’s Peak.

Askew pointed out that the findings also could help people at lower altitudes who want to lose weight while preserving their lean body mass, or who are elderly and don’t eat or exercise enough to maintain their strength. He predicts that consumers might one day see leucine-rich bars on grocery store shelves, especially at high-altitude locations, such as Aspen and Denver, where high-altitude skiing and climbing activities are popular.

In the other Everest report, John Finley, Ph.D., described a study in which he gave Mt. Everest climbers a type of fat called “medium-chain triglycerides” in their cookies and hot chocolate. They also took an aspirin every day.

“We tried to improve climbers’ performances by feeding them medium-chain triglycerides — fat that we thought would be metabolized better as quick energy,” said Finley, who is with Louisiana State University.

At high altitudes, the air pressure is low and the oxygen is less dense — making less oxygen available for breathing. In response, the body makes more oxygen-carrying red blood cells. This thickens the blood and puts a strain on the heart and lungs, increasing the risk of potentially dangerous blood clots. That’s why Finley also had the climbers take aspirin, which is known for thinning the blood and reducing the risks of having a heart attack or stroke. “We found that we could reduce the risk factors involved in having more viscous blood at high altitudes by giving the climbers aspirin,” he said.

Finley himself went on the climb and collected urine and fecal samples. The climbers who consumed the medium-chain triglycerides lost less weight and performed better than others on the expedition. The data also suggested that fats aren’t absorbed well at high altitudes when the body is losing a lot of weight, possibly because too little bile is produced by the liver to dissolve the fats, he explained.

Finley doesn’t have plans to commercialize the medium-chain triglyceride hot chocolate and cookies, but suggests that people going to high-altitude locations talk with their health-care providers about taking a daily aspirin.

Provided by American Chemical Society (news : web)

New salts for chemical soups

Organozinc reagents are an important class of organometallic compounds with a wide range of applications. German chemists have developed a novel route for the synthesis of so-called organozinc pivalates in a stable powdered form. They promise to be extremely useful in many industrial contexts.

In order to meet future demands for new pharmaceuticals, innovative materials and agricultural pesticides, the chemical industry is dependent on the ongoing development of effective methods for the synthesis of complex organic compounds. Because they are so versatile, organometallic molecules are of special significance in this context. Among these, reagents containing zinc atoms have certain advantages over the corresponding organolithium or -magnesium compounds, as they are compatible with a broader array of functional groups.

Ludwig-Maximilians-Universitat Munchen chemists led by Professor Paul Knochel have now developed a simple "one-pot" method for the economical synthesis of organozinc pivalates. Up until now, such functionalized organozinc compounds were only available in liquid form, and were difficult to transport and store due to their susceptibility to degradation upon contact with air or moisture. The new synthetic route permits their formation as salt-stabilized solids, which can easily be recovered in powder form. "In this form, the reagents can be stored in an argon atmosphere for months without loss of activity," says Knochel. "They can even be exposed to air for short periods without risk of degradation or ignition."

One of the most prominent applications for organozinc reagents is their use for the so-called Negishi cross-coupling, a type of reaction that provides a simple means of linking carbon atoms together in a virtually unlimited variety of ways, and earned its discoverer a share of the Nobel Prize for Chemistry in 2010. "The new class of organozinc pivalates makes it possible to employ different solvents in the Negishi cross-coupling reaction and greatly extends the spectrum of coupling partners it can be applied to," says Sebastian Bernhardt, who is the lead author on the new study. "The new reagents contain magnesium salts, which also facilitate the addition of organozinc pivalates to carbonyl groups." This opens the way to their use for a whole series of applications relevant to the industrial manufacture of fine chemicals. The new scheme for synthesis of these compounds is the subject of an international patent application. (suwe)

More information: Preparation of Solid Salt-Stabilized Functionalized Organozinc Compounds and their Application to Cross-Coupling and Carbonyl Addition Reactions
Sebastian Bernhardt, Georg Manolikakes, Thomas Kunz, Paul Knochel; Angewandte Chemie International Edition, August, 24, 2011,

Provided by Ludwig-Maximilians-Universitat Munchen

Genetic code used to engineer a living protein

Yale University researchers have successfully re-engineered the protein-making machinery in bacteria, a technical tour de force that promises to revolutionize the study and treatment of a variety of diseases.

"Essentially, we have expanded the genetic code of E. coli, which allows us synthesize special forms of proteins that can mimic natural or disease states," said Jesse Rinehart of the Department of Cellular and Molecular Physiology and co-corresponding author of the research published in the August 26 issue of the journal Science.

Since the structure of DNA was revealed in the 1950s, scientists have been working hard to understand the nature of the genetic code. Decades of research and recent advances in the field of synthetic biology have given researchers the tools to modify the natural genetic code within organisms and even rewrite the universal recipe for life.

"What we have done is taken synthetic biology and turned it around to give us real biology that has been synthesized," Rinehart explained.

The Yale team — under the direction of Dieter Söll, Sterling Professor of Molecular Biophysics and Biochemistry, professor of chemistry and corresponding author of the paper — developed a new way to influence the behavior of proteins, which carry out almost all of life's functions. Instead of creating something new in nature, the researchers essentially induced phosphorylation, a fundamental process that occurs in all forms of life and can dramatically change a protein's function. The rules for protein phosphorylation are not directly coded in the DNA but instead occur after the protein is made. The Yale researchers fundamentally rewrote these rules by expanding the E. coli genetic code to include phosphoserine, and for the first time directed protein phosphorylation via DNA.

This new technology now enables the production of human proteins with their naturally occurring phosphorylation sites, a state crucial to understanding disease processes. Previously, scientists lacked the ability to study proteins in their phosphorylated or active state. This has hindered research in diseases such as cancer, which is marked by damagingly high levels of protein activation.

"What we are doing is playing with biological switches — turning proteins on or off — which will give us a completely new way to study disease states and hopefully guide the discovery of new drugs," Rinehart said.

"We had to give some very ancient proteins a few modern upgrades," Söll said.

Söll and Rinehart now are attempting to create proteins in states known to be linked to cancer, type 2 diabetes, and hypertension. Both men, however, stressed the technique can be done for any type of protein.

"Dr. Söll and his colleagues have provided researchers with a powerful new tool to use in uncovering how cells regulate a broad range of processes, including cell division, differentiation and metabolism," said Michael Bender, who oversees protein synthesis grants at the National Institute of General Medical Sciences of the National Institutes of Health.

Provided by Yale University (news : web)

Scientifically taking the guilt out of guilty pleasures

Red wine and chocolate are part of the working week for Australian Institute for Bioengineering and Nanotechnology researcher Dr. Aaron Micallef.

More specifically, Dr. Micallef has designed and prepared new compounds that mimic the activity of antioxidants found in wine and chocolate.

He hopes the compounds can promote the body's natural antioxidant defences, neutralise damaging free radicals in the body and fight the onset of diseases associated with free radical damage, such as heart disease and arthritis.

To mark National Science Week, Dr. Micallef will explain the research as part of a wine and chocolate tasting event at the Queensland Museum at South Bank on August 26.

He will talk about antioxidants, wine and chocolate; their relationship to his AIBN research; and his role as a free radical chemist and associate investigator for the ARC Center of Excellence for Free Radical Chemistry and Biotechnology.

“I want people to realise there are links between chemistry, chemical research, the foods we eat and our health,” Dr. Michallef said.

“Free radicals are implicated in many processes in the body, such as inflammation, ageing and cancer. They can be very damaging, but we are conducting research into how we can use antioxidants to neutralise free radicals and prevent this damage," he said.

“Eating foods rich in antioxidants can help mop up damaging free radicals in the body. It means we are taking the guilt out of pleasures such as red wine and chocolate.

“I have a soft spot for a good glass of red wine and dark chocolate myself, so the research is definitely very appealing.”

Reactive free radicals are believed to be the cause of the accumulated damage in cells that contributes to ageing and degenerative diseases. Antioxidants can protect against this damage, either neutralising the radicals directly or promoting the body's natural antioxidant defences.

Dr. Micallef said his synthetic compounds would have potential applications in fighting disease if they were found to mimic the protective properties of the antioxidants found in red wine and chocolate.

Called Radical Wine and Chocolate, the tasting event will be held at the Queensland Museum from 5.30pm on August 26, with three guest speakers and tastings and sales of wines from Ballandean Estate and Sirromet Winery. Chocolates to taste and buy will be from Bittersweet, Mayfield and Ballandean Estate.

Provided by University of Queensland (news : web)