Biographical Memoirs Volume 56 (1987) / Chapter Skim
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Merton Franklin Utter
Merton Franklin Utter
Pages 474-499
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that this concept is incorrect. They discovered phosphoenolpyruvate carboxykinase and pyruvate carboxylase, two enzymes that in concert convert pyruvate to phosphoenolpyruvate by a sequence that differs from the glycolytic pathway.
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Prior to his death, Utter's studies had increasingly centered on the interface between disease processes and basic biochemistry. His laboratory was considered one of the leading centers studying inborn errors in the metabolism of pyruvate, and his collaboration was constantly sought by clinical investigators anxious to verify the absence of specific enzymes in patients suffering from various cTiseases.
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In 1956 Merton Utter was promoted to professor, and in 1965 he became chairman of the Biochemistry Department ant] continued in that position until 1976.
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not been demonstrated in bacteria, ant] consideration of their intermediary metabolism was in large part based on what was known from studies of enzymes from yeast anct animal tissue.
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At about the same time, a mass spectrometer for measurement of i3C was being constructed by the group in the laboratory, as well as a thermal diffusion column five stories high for concentration of this stable isotope. It was the ingenuity and hard work of graduate students such as Merton Utter that made the laboratory of C
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In 1943 Utter published "The Role of Phosphate in the Anaerobic Dissimilation of Pyruvic Acid" and in 1944 the "Formation and Reactions of Acety~phosphate in Escherichia coli" and "Reversibility of the Phosphorociastic Split of Pyruvate." (At that time, Fritz Lipmann had just discoverecI the role of acety~phosphate in metabolism.) Anyone who is familiar with the history of biochemistry recognizes from the titles that Merton Utter's early work was at the forefront of biochemistry, just as it has been at the forefront of carbohyctrate metabolism to this clay.
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Subsequently, the enzyme was named the malic enzyme and shown to catalyze the following reaction: malic enzyme CON + pyruvate + NADPH ~ ~ malate + NADP Following this discovery, Ochoa and collaborators suggested that this enzyme catalyzed the primary reaction in the fixation of CO2 and that oxalacetate is former! by coupling the following two reactions: malic enzyme CO' + pyruvate + NADPH ~ ~ malate + NADP malic dehydrogenase Malate + NAD _ - oxalacetate + NADH Sum: CO, + pyruvate + NADPH + NAD ~ oxalacetate + NADP + NADH Ephraim Racker summarized the status of work in this field at a meeting on CO2 fixation in 1950, when he proposed a toast to the "wouldn't work reaction." Although the enzymatic basis for the Wood and Werkman reaction continued to be elusive, Utter and K
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inclepenclently proposed that pyruvate might be converted to P-enolpyruvate by the combined action of the malic enzyme and P-enolpyruvate carboxykinase by the following sequence: malic enzyme Pyruvate + CO2 + NADPH ~ ~ malate + NADP malic dehydrogenase Malate + NAD - oxalacetate + NADH P-er~olpyruvate Oxalacetate + GTP ~ - P-enolpyruvate + GDP + CO2 carboxykinase Sum: Pyruvate + GTP + NADPH + NAD > P-enolpyruvate + GDP + NADP + NADH The thermodynamics of this sequence are not particularly favorable, but by coupling the oxidation of NADH to other reactions it was considered possible to maintain a high ratio of NADPH/NAD, thereby favoring the synthesis of the P-enolpyruvate.
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Utter tract thus found the enzymatic basis of the "wouldn't work reaction," twenty-five years after it had been postulated as a possible mechanism for the formation of dicarboxylic acids by CO2 fixation. Pyruvate carboxylase, when coupled with Penolpyruvate carboxykinase, catalyzecI the formation of Penolpyruvate as illustrated below.
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for control of metabolic pathways and remains a major legacy of Merton Utter's scientific work. Structure of Biotin Enzymes.
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Although there is not complete agreement, the overall configuration of pyruvate carboxylase from chicken, sheep, anct rat appears to be a tetrahedron-like structure consisting of two pairs of subunits in different planes orthogonal to each other, with the opposing pairs of subunits interacting on their convex surfaces (F. Mayer, I
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He developed sensitive enzymatic assays for pyruvate dehy cirogenase, pyruvate carboxylase, P-enolpyruvate carboxyki nase, and pyruvate kinase using easily obtained tissues, such as cultured skin fibroblasts, reticulocytes, or lymphocytes. He was able to demonstrate, for example, that contrary to the prevailing opinion, Leigh's disease clid not involve a clefi ciency in pyruvate carboxylase.
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judicious manner made him a valued member of numerous national panels concerned with research policy. Merton Utter spent virtually his complete university career as a member of the Department of Biochemistry at Case Western Reserve University School of Medicine.
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, 1953-1954 Paul Lewis Award in Enzyme Chemistry, 1956 National Science Foundation Senior Research Fellow (Oxford) , 1960-1961 National Science Foundation Senior Research Fellow (Leicester)
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MERTON FRANKLIN UTTER PROFESSIONAL SOCIETIES American Society of Biological Chemists American Association for the Advancement of Science American Chemical Society American Society of Microbiologists Biochemical Society (England) New York Academy of Sciences Society of Experimental Biology and Medicine 489
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Dissimilation of phosphoglyceric acid by Escherichia coli. Biochem.
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Purification of oxalacetic carboxylase from chicken liver.
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Equilibrium and kinetic studies of the pyruvic kinase reaction.
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Pyruvate carboxylase. VII A possible role for tightly bound manganese.
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Secondary activation effects of mitochondrial isocitrates dehydrogenases from yeast. Biochim.
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Pyruvate carboxylase from chicken liver. Steady state kinetic studies indicate a "two-site" ping pony mechanism.
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Noce. Decarboxylation of oxalacetate to pyruvate by purified avian liver phosphoenolpyruvate carboxykinase.
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Eject of thyroid hormone on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase.
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The mitochondrial and cytosolic forms of avian phosphoenolpyruvate carboxykinase (GTP) are encoded by different messenger RNAs.
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Frey. Stereochemical course of thiophosphoryl group transfer catalyzed by mitochondrial phosphoenolpyruvate carboxykinase.
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