Mary Ellen Jones

Bio: Mary Ellen Jones is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Carbamyl Phosphate & Orotate phosphoribosyltransferase. The author has an hindex of 42, co-authored 101 publications receiving 5453 citations. Previous affiliations of Mary Ellen Jones include University of South Carolina & Brandeis University.

Pyrimidine Nucleotide Biosynthesis in Animals: Genes, Enzymes, and Regulation of UMP Biosynthesis

Abstract: PERSPECfIVES AND SUMMARY 253 INTRODUCfION 256 GENES AND PROTEIN PRODUCfS 257 Drosophila 257 Mammals 258 Multienzyme pyr1-3 258 DBO dehydrogenase 260 Multienzyme pyrj,6 260 CHARACfERlSTICS OF DHOdeHase AND MULTIENZYMES pyrI-3 AND pyrS,6 262 Activities of Multienzyme pyrl-3 262 Carbamyl phosphate synthetase 262 Aspartate transcarbamylase 263 Dihydroorotase 263 Dihydroorotate Dehydrogenase 266 Activities of Multienzyme pyrS,6 266 REGULATION OF UMP BIOSYNTHESIS 269 Regulation by Metabolites 269 Regulation by Orotic Acid and Orotidine Accumulation 273 Channeling of CA�P, CAasp, and aMP 275

Energy conservation in chemotrophic anaerobic bacteria.

Abstract: [This corrects the article on p. 100 in vol. 41.].

Low-barrier hydrogen bonds and enzymic catalysis

Abstract: Formation of a short (less than 2.5 angstroms), very strong, low-barrier hydrogen bond in the transition state, or in an enzyme-intermediate complex, can be an important contribution to enzymic catalysis. Formation of such a bond can supply 10 to 20 kilocalories per mole and thus facilitate difficult reactions such as enolization of carboxylate groups. Because low-barrier hydrogen bonds form only when the pKa's (negative logarithm of the acid constant) of the oxygens or nitrogens sharing the hydrogen are similar, a weak hydrogen bond in the enzyme-substrate complex in which the pKa's do not match can become a strong, low-barrier one if the pKa's become matched in the transition state or enzyme-intermediate complex. Several examples of enzymatic reactions that appear to use this principle are presented.

A proficient enzyme

Abstract: Orotic acid is decarboxylated with a half-time (t1/2) of 78 million years in neutral aqueous solution at room temperature, as indicated by reactions in quartz tubes at elevated temperatures. Spontaneous hydrolysis of phosphodiester bonds, such as those present in the backbone of DNA, proceeds even more slowly at high temperatures, but the heat of activation is less positive, so that dimethyl phosphate is hydrolyzed with a t1/2 of 130,000 years in neutral solution at room temperature. These values extend the known range of spontaneous rate constants for reactions that are also susceptible to catalysis by enzymes to more than 14 orders of magnitude. Values of the second-order rate constant kcat/Km for the corresponding enzyme reactions are confined to a range of only 600-fold, in contrast. Orotidine 59-phosphate decarboxylase, an extremely proficient enzyme, enhances the rate of reaction by a factor of 10(17) and is estimated to bind the altered substrate in the transition state with a dissociation constant of less than 5 x 10(-24) M.

Homocysteine Impairs the Nitric Oxide Synthase Pathway Role of Asymmetric Dimethylarginine

Abstract: Background—Hyperhomocysteinemia is a putative risk factor for cardiovascular disease, which also impairs endothelium-dependent vasodilatation. A number of other risk factors for cardiovascular disease may exert their adverse vascular effects in part by elevating plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. Accordingly, we determined if homocysteine could increase ADMA levels. Methods and Results—When endothelial or nonvascular cells were exposed to DL-homocysteine or to its precursor L-methionine, ADMA concentration in the cell culture medium increased in a dose- and time-dependent fashion. This effect was associated with the reduced activity of dimethylarginine dimethylaminohydrolase (DDAH), the enzyme that degrades ADMA. Furthermore, homocysteine-induced accumulation of ADMA was associated with reduced nitric oxide synthesis by endothelial cells and segments of pig aorta. The antioxidant pyrrollidine dithiocarbamate preserved DDAH activity and reduced ADMA accumulation. Moreover, homocysteine dose-dependently reduced the activity of recombinant human DDAH in a cell free system, an effect that was due to a direct interaction between homocysteine and DDAH. Conclusion—Homocysteine post-translationally inhibits DDAH enzyme activity, causing ADMA to accumulate and inhibit nitric oxide synthesis. This may explain the known effect of homocysteine to impair endothelium-mediated nitric oxide– dependent vasodilatation. (Circulation. 2001;104:2569-2575.)