- Alternating conformations and switching tasks, a dimer’s oppositely oriented halves relieve the cellular stress that can build up when molecular oxygen is used for power generation. When one half of the dimer acts like a proton pump, the other half converts NADH to NADP+—and vice versa.Both of these mutually exclusive tasks are necessary to create NADPH, which is used for amino acid biosynthesis and to remove reactive oxygen species. Yet somehow both tasks are accomplished by one enzyme, nicotinamide nucleotide transhydrogenase (TH).The details of TH’s task juggling ways emerged from structural studies of the ancient enzyme, which is found throughout the animal kingdom as well as in plants and many simpler species. In humans and other higher organisms, TH works within mitochondria, the tiny double-hulled oxygen reactors that help power most cellular processes.Although oxygen is great for efficient energy production, it has a serious downside: the accumulation of reactive oxygen species. These have been linked with diseases such as diabetes, cancer, and Alzheimer's and Parkinson's diseases, as well as with cell death and aging. To support their use of oxygen, cells have had to evolve defense mechanisms, of which TH is a part.TH has long been thought to participate in the production of NADPH, which is crucial for defusing oxygen-free radicals. But TH has been hard to study. It has exceptionally loose structural components, and so it is difficult to evaluate using X-ray crystallography. With its structure poorly understood, TH has given up few functional secrets.Until recently. In the January 9 issue of Science, researchers based at The Scripps Research Institute (TSRI) presented a new structural model for TH, which they used to support speculation about TH’s mechanisms. The details, which appeared in an article entitled, “Division of labor in transhydrogenase by alternating proton translocation and hydride transfer,” included the structure of TH’s transmembrane portion and the way in which TH’s parts relate to the enzyme’s whole.“We present the 2.8 Å crystal structure of the transmembrane proton channel domain of TH from Thermus thermophilus and the 6.9 Å crystal structure of the entire enzyme (holo-TH),” wrote the authors. “The membrane domain crystallized as a symmetric dimer, with each protomer containing a putative proton channel.”Most interesting were revelations about TH’s “domain III” structures. These appear directly above TH’s transmembrane structure, just inside the mitochondrial matrix. They serve to bind NDPH’s precursor molecule, NADP+, during conversion to NADPH. Structural biologists haven't understood how two such structures could work side by side in the TH dimer and not interfere with each other's activity. The new structural data suggest that these side-by-side structures are highly flexible and always have different orientations.“Our most striking finding was that the two domain III structures are not symmetric—one of them faces up while the other faces down," said Josephine H. Leung, first author of the Science article and a graduate student in the laboratory of C. David Stout, Ph.D., an associate professor at TSRI.One of structures is oriented apparently to catalyze the production of NADPH, while the other is turned toward the membrane, perhaps to facilitate transit of a proton. The new structural model suggests that with each proton transit, the two domain III structures flip and switch their functions. "We suspect that the passage of the proton is what somehow causes this flipping of the domain III structures," Leung noted."Despite its importance, TH has been one of the least studied of mitochondrial enzymes," stated Dr. Stout. "Our new study helps clear up some mysteries—suggesting how the enzyme structure might harness protons and indicating that its two sides are able to alternate functions, always staying in balance."
- Kaynak: http://www.genengnews.com/gen-news-highlights/dynamic-duo-a-dimeric-enzyme-clobbers-oxidative-stress/81250786/
Female mice that are fed a comparable human dose of fructose have both their reproductive abilities and their lifespans cut shorter than those that are fed regular table sugar or sucrose, new research shows.
“This is the most robust study showing there is a difference between high-fructose corn syrup and table sugar at human-relevant doses,” said biologist Wayne Potts from the University of Utah in the US, who led the study, in a press release.
Interestingly, the study found that there was no difference in the affects of fructose and normal sugar in male mice, which the researchers believe may indicate that both sugars are equally toxic to males.
The results which are being published in The Journal of Nutrition, and they’re worrying, as high-fructose corn syrup is now found in many processed foods, from soft drinks to muesli bars.
While many studies have shown that both types of sugar aren’t great for you, the team was interested in investigating whether their affects differed. Previous studies had suggested that fructose was worse for animals - but hadn’t tested the sugars in the way humans normally consume them.
And it turns out that high-fructose sugar blends and table sugar are chemically quite distinct. Corn syrup contains far higher levels of fructose than glucose, which means the two remain as separate molecules called monosaccharides. But, in the white powdered table sugar we use when baking, there are roughly equal parts of fructose and glucose, and they bond to form a disaccharide compound.
To figure out how the two sugars affected mice, the researchers looked at mice that were either fed a diet where 25 percent of the calories were in the form of high-fructose and glucose monosccharides, like the type found in corn syrup, or where 25 percent came from table sugar.
This is comparable to the percentage of calories the average American consumes each day from added sugar, which ranges from 13 to 25 percent. And almost half of that comes from high-fructose sugars found in cane syrup.
“When the diabetes-obesity-metabolic syndrome epidemics started in the mid-1970s, they corresponded with both a general increase in consumption of added sugar and the switchover from sucrose being the main added sugar in the American diet to high-fructose corn syrup making up half our sugar intake,” explained Potts in the release.
The team then studied the two groups of mice for 40 weeks and observed how long the mice lived, how many children they had and how well they managed to hang on to their mice “houses” while competing with other individuals.
The female on the high-fructose diet had 1.87 times higher death rates than those on the sucrose diet, and they also produced 26.4 percent fewer children, suggesting that their reproductive rates had been affected.
The males showed no difference, but a study by the same group in 2013 found that males that were fed a high-fructose diet were less likely to be able to reproduce and hold their territory than those that were fed starch, which suggests that sugar in general is bad for the guys.
But regardless of the sex of the mice, there was no difference between the two diet groups when it came to how much they ate, weight gain and glucose intolerance.
The scientists still aren’t sure exactly what’s causing the difference in the two types of sugars, but table sugar, or sucrose, is broken down into monosaccharides before the body absorbs it, so whatever is causing the difference must be occurring before the food is absorbed.
“So we speculate that the different sugars could favour different microbes in the guts of mice. Other research has shown differences in bacterial communities in the gut to be associated with metabolic diseases in rodents and in humans. It’s possible one form of sugar causes more bacteria to get across your gut than another,” said James Ruff, the study’s first author, in the release.
Obviously there's a lot more research to be done on what the affect of these sugars is on humans, but it's interesting research to consider next time you reach for a second can of coke.
Kaynak:http://www.sciencealert.com/fructose-is-more-toxic-than-table-sugar-and-cuts-lifespan-and-reproduction-of-female-mice
