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Robert Gerson Shulman (born March 3, 1924) is an American biophysicist and Sterling Professor Emeritus of Molecular Biophysics and Biochemistry and a senior research scientist at the Department Diagnostic Radiology at Yale University. [1]
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Robert Gerson Shulman (born March 3, 1924) is an American biophysicist and Sterling Professor Emeritus of Molecular Biophysics and Biochemistry and a senior research scientist at the Department Diagnostic Radiology at Yale University. [1]
Shulman was born in New York City and in 1943 graduated Phi Beta Kappa from Columbia University where he majored in chemistry and studied literature with Lionel Trilling, who encouraged Shulman's life-long interest in the humanities. After graduating, Shulman joined the United States Navy Reserve. He served in the Pacific during the last days of World War II as a Lt,jg USNR on the USS Saratoga. After the war he entered Columbia as a graduate student. His wartime work with radar brought him to the lab of Charles Townes, who was working with microwave spectroscopy. In a 2019 oral history, Shulman said: "When [Townes] was a physics student at Cal Tech, there was a book on electricity and magnetism ...and Charlie had read that book, and proofread it, and he had solved all the problems presented in the book to make sure that they were done properly. So he was the most thorough, best-studied scientist I knew." Shulman received his Ph.D. in Chemistry at Columbia in 1949, and from 1949 to 1950 was a fellow at California Institute of Technology. At Cal Tech he met Alex Rich, his roommate, who worked with Linus Pauling. “They were a grand bunch of scientist-professors there, many of whom became my heroes. Once I finally went into biology I really appreciated what they did and how wonderful they were.” (2019 Oral History)
After this postdoc year, Dr. Shulman took a job at Howard Hughes' Hughes Aircraft, working with Harper Q. North who was running the company's semi-conductor program as part of the research group producing the Hughes Germanium Diodes, which were marketed as "Fusion-sealed in a glass." In 1953, he joined the physics research department at Bell Telephone Laboratories in Murray Hill, N.J., where he began research on the use of NMR in condensed matter physics particularly studying magnetic materials like paramagnetic fluorides where he defined the covalent bonds and the exchange reactions responsible for their anti-ferromagnetism in these primarily ionic compounds. Eventually he became interested in Russian claims that DNA was a magnetic material which he showed were mistaken. In 1961 he received a Guggenheim Fellowship to study abroad as a visiting Professor of Physics at the Ecole Normale in Paris which, because his interests had shifted to biological materials, he transferred, with the blessing of the Guggenheim, to the Laboratory for Molecular Biology in Cambridge. "There was all sorts of speculation about DNA," he said while still at Bell Labs "so I went back to Alex Rich, who was by then an established biologist. I said, 'I'd like to go into biology, where should I go on my sabbatical?' The answer was 'Go work with Francis Crick if you can.'"[ citation needed ] In 1961–1962, he worked with Crick and Sidney Brenner in Cambridge, "in the old courtyard of the Cavendish Lab", helping to put "the finishing touches to Crick’s hypothesis as to how the DNA code was read for synthesizing proteins".[ citation needed ]
At Cambridge talking about what experiments to do next about how the genetic code was read, Francis walked around saying, "I feel as if at any minute the whole hypothesis is going to go down the drain. We'll do an experiment and it will disprove it all, and we'll be left with nothing."[ citation needed ] "I feel it every day I come in here, frightened by that."[ citation needed ] And that was such a wonderful thing to have heard about science. ..."I realize this is a hypothesis. We’re doing experiments that support the hypothesis, and it gives us confidence that the hypothesis is an accurate description of the world, some part of the world. But it's a hypothesis and we must never forget that. There was timidity, tentativeness in Francis's attitude towards scientific results, in that despite the success of his creative hypotheses he remained open to any results that will disprove it. And so it was really a lovely illustration of what science could be." (2019 Oral History). Another day Francis, in a discussion, said we could do Sidney's experiment which meant trying to experimentally identify chain terminators in the DNA which I volunteered to do and with guidance from Leslie Barnett managed to accomplish. But instead of continuing in Molecular Biology I was more interested in charting new directions for biological NMR and returned to Bell Labs to follow NMR and other spectroscopic studies of biological materials and organisms. With Terry Eisinger and Bill Blumberg I built up a group of young scientists which eventually became the Biophysical Research Department. Over several decades, we pioneered in the use of nuclear magnetic resonance (NMR), magnetic resonance imaging (MRI), other forms of spectroscopy and EXAFS to study biochemical processes. The research soon focused on non-invasive nuclear magnetic resonance studies in vivo of humans and animals [2]
A propos of the direction he took on returning to Bell Labs, Dr. Shulman said, "I note that at that time (1962) metabolism had yielded center stage of biological research to the genetics made available by Crick’s DNA findings. However, I proposed to study metabolism which had been the traditional function of biochemistry, at that time generally ignored in the search for genetic knowledge, but which I felt could be re invigorated by the physical methods developed at Bell Labs. In this way I was combining the development of a physical technique with an extension of its applicability to biological problems by which I followed the practices of the two world-famous laboratories where I had worked. With that intention I returned to Bell Labs and started a biophysics department which attracted a wonderful group of scientists, where we studied biomolecules and developed in vivo methods of following by NMR the biochemical pathways of stable isotopes. Members of this Department subsequently went on to exciting developments, on their own, which earned one Nobel Prize, Kurt Wuthrich, the invention of fMRI by Seiji Ogawa, and of neural nets by John Hopfield.” (2019 Oral History). They extended NMR in vivo and filled many important positions in academia, industry and government.ral History)
Dr. Shulman joined the faculty at Yale in 1979. [3] He was a Guggenheim Fellow in 1962. He is a member of the National Academy of Sciences and the Institute of Medicine. To the surprise of his new colleagues, he left the study of biomolecular structure in favor of in vivo pathways. "Helped from the beginning by Jeff Alger, Kamil Ugurbil and Jan den Hollander and soon after by Kevin Behar and Doug Rothman, the first of several graduate students, we continued the studies of in vivo metabolism in yeast, human muscle and brain. Yeast studies were conducted during the 1980s and their results were the basis of a Metabolic Control Analysis of glucose pathways of yeast in 2015 and 2020. Human muscle studies led to the important result that kinase activities changed the activity of enzymes not, as usually considered, to control pathway flux but to maintain homeostasis of biochemical intermediates. This established the ability to measure glycogen in vivo which, with the cooperation of two clinical colleagues, Gerry Shulman and Ralph De Fronzo, and actually performed by Doug Rothman who had become the scientific strength of our effort, was used to measure glucose pathways in Type 2 Diabetics as compared to controls. This showed that the flux of glycogen synthesis, which stored glucose as muscle glycogen, was controlled, not by Glycogen Synthase, as had been assumed, but by glucose transporters that were inadequately mobilized in Type 2 patients, and has subsequently been developed by Doug Rothman and Gerry Shulman as the mechanism of this prevalent pathology. "13CNMR studies of the human brain, once again led by Doug Rothman, measured the flux of the glutamate/glutamine cycle thereby quantitatively unifying electrical, neurotransmitter and electrical brain measurements which now form the basis of brain function. To the extent that these in vivo measurements of brain, yeast and muscle have succeeded in showing the powers of NMR and other spectroscopic measurements of energy the goal that I set in 1962 of unifying the strengths of Bell Labs and the LMB of Cambridge is being reached. In addition to the collaborators mentioned or unfortunately neglected in this account thanks are due to the Guggenheim Foundation whose far-sighted understanding of science made it possible." He was a Guggenheim Fellow in 1962. He is a member of the National Academy of Sciences and the Institute of Medicine (Now The National Academy of Medicine.
He is married to Stephanie S. Spangler, and has two surviving sons Mark R. Shulman and James L. Shulman.
Glycolysis is the metabolic pathway that converts glucose into pyruvate, and in most organisms, occurs in the liquid part of cells, the cytosol. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body.
Kurt Wüthrich is a Swiss chemist/biophysicist and Nobel Chemistry laureate, known for developing nuclear magnetic resonance (NMR) methods for studying biological macromolecules.
Phosphoglucomutase is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction.
The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The small molecule chemicals found in a given metabolome may include both endogenous metabolites that are naturally produced by an organism as well as exogenous chemicals that are not naturally produced by an organism.
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. In mammals, including humans, GSK-3 exists in two isozymes encoded by two homologous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction and bipolar disorder.
Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects.
Glycogen synthase is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase that catalyses the reaction of UDP-glucose and n to yield UDP and n+1.
1,4-alpha-glucan-branching enzyme, also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the GBE1 gene.
The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.
Alexander J. Varshavsky is a Russian-American biochemist and geneticist. He works at the California Institute of Technology (Caltech) as the Morgan Professor of Biology. Varshavsky left Russia in 1977, emigrating to United States.
The history of biochemistry can be said to have started with the ancient Greeks who were interested in the composition and processes of life, although biochemistry as a specific scientific discipline has its beginning around the early 19th century. Some argued that the beginning of biochemistry may have been the discovery of the first enzyme, diastase, in 1833 by Anselme Payen, while others considered Eduard Buchner's first demonstration of a complex biochemical process alcoholic fermentation in cell-free extracts to be the birth of biochemistry. Some might also point to the influential work of Justus von Liebig from 1842, Animal chemistry, or, Organic chemistry in its applications to physiology and pathology, which presented a chemical theory of metabolism, or even earlier to the 18th century studies on fermentation and respiration by Antoine Lavoisier.
UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme involved in carbohydrate metabolism. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,
Enzyme activators are molecules that bind to enzymes and increase their activity. They are the opposite of enzyme inhibitors. These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. An example of an enzyme activator working in this way is fructose 2,6-bisphosphate, which activates phosphofructokinase 1 and increases the rate of glycolysis in response to the hormone glucagon. In some cases, when a substrate binds to one catalytic subunit of an enzyme, this can trigger an increase in the substrate affinity as well as catalytic activity in the enzyme's other subunits, and thus the substrate acts as an activator.
In vivo magnetic resonance spectroscopy (MRS) is a specialized technique associated with magnetic resonance imaging (MRI).
Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.
Functional magnetic resonance spectroscopy of the brain (fMRS) uses magnetic resonance imaging (MRI) to study brain metabolism during brain activation. The data generated by fMRS usually shows spectra of resonances, instead of a brain image, as with MRI. The area under peaks in the spectrum represents relative concentrations of metabolites.
Glycogen phosphorylase, liver form (PYGL), also known as human liver glycogen phosphorylase (HLGP), is an enzyme that in humans is encoded by the PYGL gene on chromosome 14. This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 14. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Feb 2011].
Rolf Gruetter is a Swiss physicist and neurobiologist specialized in magnetic resonance, biomedical imaging and brain metabolism. He is a professor of physics at EPFL and the head of the Laboratory Functional and Metabolic Imaging at the School of Basic Sciences.