Findings are informing human research into rare, sometimes fatal disease
Glycogen storage disorders, which affect the body’s ability to process sugar and store energy, are rare metabolic conditions that frequently manifest in the first years of life. Often accompanied by liver and muscle disease, this inability to process and store glucose can have many different causes, and can be difficult to diagnose.
Now, researchers at the University of Missouri who have studied enzymes involved in metabolism of bacteria and other organisms have catalogued the effects of abnormal enzymes responsible for one type of this disorder in humans. Their work could help with patient prognosis and in developing therapeutic options for this glycogen storage disease.
“In February of this year, I found an article in the New England Journal of Medicine (NEJM) that caught my eye,” said Lesa Beamer, associate professor of chemistry and biochemistry at MU. “It was a landmark study identifying a new, inherited metabolic disorder in humans called phosphoglucomutase 1 (PGM1) deficiency, and affects the human versions of the very same enzymes I had studied.”
The NEJM study was the first to characterize the multiple effects of the disorder in humans and pinpointed the enzyme involved. The disorder, described initially in 21 patients, is considered rare but will likely be found more often now that genetic tests have been developed.
According to the study, the disease often affects patients in early childhood or adolescence, and can cause hypoglycemia, muscle disease, hormonal abnormalities, and cardiac problems. Many patients exhibit exercise intolerance and, because the condition could not previously be diagnosed, these problems sometimes led to early deaths.
Beamer’s lab researches similar enzymes in bacteria that play important roles in carbohydrate (sugar) metabolism, including sugars like glucose. These enzymes perform the same chemical reaction as the human protein involved in the newly identified inherited disease, and share many other similarities.
“Once the disease involving the human equivalent had been identified, we were able to put the knowledge we’ve gained to immediate use,” Beamer said. “Using the information provided by the NEJM study, we recreated the mutated proteins that cause the disorder in a test tube, and conducted detailed biochemical analyses.
Our study was the first to systematically characterize and index these mutant proteins for comparison with the symptoms in human patients. Because patient studies are complex and time-consuming, our biochemical analyses are proving essential to understanding the complicated clinical presentation of this inherited disorder.”
The early-stage results of this research are promising. If additional studies are successful, Beamer believes that her bacterial enzyme research could assist with further research studying the development of human genetic health tests and therapeutics within the next few years. Her lab currently is collaborating with human medical researchers to “fast track” the study of this rare disease.
Beamer holds joint appointments in the Department of Chemistry in the College of Arts and Science and the Department of Biochemistry in the School of Medicine and the College of Agriculture, Food and Natural Resources at MU.
The study, “Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency,” was funded in part by the National Science Foundation (Award: MCB-1409898) and was published in The Journal of Biological Chemistry.”
Jeff Sossamon | EurekAlert!
Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University
Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
27.03.2017 | Earth Sciences
27.03.2017 | Life Sciences
27.03.2017 | Life Sciences