Biographical Memoirs Volume 79 (2001) / Chapter Skim
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Mary Ellen Jones
Mary Ellen Jones
Pages 182-201
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From page 183... ...
to demonstrate talent for devising new analytical procedures, for cleverly designing experimental approaches, en cl for insightful analyses of the emerging information. Jones was the first woman scientist to hoist an enclowoc!
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From page 184... ...
Mary Ellen {ones was born on December 25, 1922, in La Grange, Illinois, one of four chiTciren of Elmer en c! Laura Klein {ones.
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From page 185... ...
her dissertation research uncler the supervision of Joseph Fruton, completing her studies in only three years while characterizing the catalytic properties of cathepsin C Fruton was a very helpful mentor en cl instillecl in her the paradigms for goocl experimental design.
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From page 186... ...
She died in Waltham, Massachusetts, on August 23, 1996. Mary Ellen {ones was an energetic and almost tireless worker, highly flexible, and yet very focused.
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From page 187... ...
that the reaction mechanism involvecl an enzyme-aclenylate intermediate. When some years later DNA polymerase was first being characterized by Arthur Kornberg and his colleagues, they would observe a similar reaction with a pyrophosphoryl cleavage of the nucleoticle precursors, thereby helping to establish the general nature of the mechanism clescribec!
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From page 188... ...
By inclucling the enzyme carbonic anhycirase, they were able to demonstrate that bicarbonate was the immediate substrate for the carboxy phosphate step in the synthesis of carbamoyl phosphate.
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From page 189... ...
In 1955 it was completely unclear as to whether the synthesis began with the formation of carboxyphosphate and whether this came from bicarbonate or from a carboxy! group on an amino acid, because it was already establishecl that N-acetyI-glutamate was a necessary factor in the synthesis of citrulline.
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From page 190... ...
For almost 10 years there would be uncertainty and confusion about why two ATP molecules were needed for the synthesis of carbamoyl phosphate, what the true nitrogen source was, and whether there was more than one carbamoyl phosphate-synthesizing enzyme in any specific cell or tissue. By 1967 this was largely settled, and Mary Ellen Jones had been pivotal in clarifying the most important details in Figure I
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From page 191... ...
phosphate synthetase activity in mouse tumor cells by reaclily measuring i4C-bicarbonate incorporation into carbon 2 of uracil (1965~. This experimental design was excellent, as it combinecl a tissue source likely to have higher enzyme levels (tumors consume nucleoticles more steaclily)
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From page 192... ...
In the following year Jones and Hager reported the first isolation of the glutamine- dependent carbamoyl phosphate synthetase from cytoplasmic extracts of Ehrlich ascites cells and from rat liver (1966~. The critical factor impeding earlier efforts was now apparent with their demonstration that the enzyme was extremely unstable.
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From page 193... ...
Fetal liver had two carbamoyl phosphate synthetase activities, now designated as CPS I and CPS II. CPS I is only in the mitochondrion and preferentially utilizes ammonia in the formation of citrulline by the enzyme ornithine carbamoyltransferase (OCT)
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From page 194... ...
Expanding these studies to eight bacterial species, they showocl that the sizes of the ACT enzymes, measured by column chromatography, suggested that there were three major classes for this enzyme in the different types of bacteria (1969~. Using the same methoclology for cell extracts from the eight bacterial species, they now characterized the three types of ACT.
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From page 195... ...
. The purification of UMP synthase from human tissue by her student Laura Livingstone was extenclecl with her postcloc B
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From page 196... ...
A clever strategy involvecl culturing cells in the presence of azauricline, a nucleosicle easily absorbed by cells, en cl then converted to azaUMP, a very strong inhibitor of OMP decarboxylase. It was anticipated that the nucleoticle wouIcl bind to the enzyme in the cells en cl thereby stabilize it cluring purification experiments.
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From page 197... ...
postcloc {uliette Bell, working in collaboration with Marion O'Leary, macle a strong case for a mechanism where cleavage of the scissile C-C bond was the rate-determining step (1990~. Using kinetic isotope effects with i3C-oMP as a function of pH, they now proposed that a proton from the enzyme was neeclec!
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From page 198... ...
She was equally quick to explore using the kinetic isotope effect as an approach to evaluating the mechanism of the enzyme. The last scientific effort of Mary Ellen {ones was a review paper that we wrote together (1996~.
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From page 199... ...
Source of carbamyl phosphate for pyrimidine biosynthesis in mouse Ehrlich ascites cells and rat liver. Science 154:422.
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From page 200... ...
Uridylic acid synthesis in Ehrlich ascites carcinoma. Properties, subcellular distribution, and nature of enzyme complexes of the six biosynthetic enzymes.
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From page 201... ...
Orotic aciduria fibroblasts express a labile form of UMP synthase.
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