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!
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
Colorectal cancer risk factors decrypted
16.07.2018 | Max-Planck-Institut für Stoffwechselforschung
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Transportation and Logistics
16.07.2018 | Agricultural and Forestry Science