Compounds and Method of Use as Anti-Infection Compounds and Therapeutic Agents to Regulate Cholesterol Metabolism

A compound is provided which comprises at least a portion of an amino acid linker-domain from squalene synthase. In alternative forms, the compound can include the amino-acid linker-domain from various fungus, including S. cerevisiae or the compound can be the functional equivalent and/or mimics an amino acid linker-domain from squalene synthase. A pharmaceutical composition includes the compound and may further include a pharmaceutical carrier. A method is provided for treating or controlling cholesterol metabolism and ergosterol metabolism in non-fungal organisms. One method includes a therapeutic treatment in humans by administering a therapeutically effective amount of the compound or pharmaceutical composition, to a patient in need of treatment, therefrom

Genomic and experimental evidence for multiple metabolic functions in the RidA/YjgF/YER057c/UK114 (Rid) protein family.

BackgroundIt is now recognized that enzymatic or chemical side-reactions can convert normal metabolites to useless or toxic ones and that a suite of enzymes exists to mitigate such metabolite damage. Examples are the reactive imine/enamine intermediates produced by threonine dehydratase, which damage the pyridoxal 5'-phosphate cofactor of various enzymes causing inactivation. This damage is pre-empted by RidA proteins, which hydrolyze the imines before they do harm. RidA proteins belong to the YjgF/YER057c/UK114 family (here renamed the Rid family). Most other members of this diverse and ubiquitous family lack defined functions.ResultsPhylogenetic analysis divided the Rid family into a widely distributed, apparently archetypal RidA subfamily and seven other subfamilies (Rid1 to Rid7) that are largely confined to bacteria and often co-occur in the same organism with RidA and each other. The Rid1 to Rid3 subfamilies, but not the Rid4 to Rid7 subfamilies, have a conserved arginine residue that, in RidA proteins, is essential for imine-hydrolyzing activity. Analysis of the chromosomal context of bacterial RidA genes revealed clustering with genes for threonine dehydratase and other pyridoxal 5'-phosphate-dependent enzymes, which fits with the known RidA imine hydrolase activity. Clustering was also evident between Rid family genes and genes specifying FAD-dependent amine oxidases or enzymes of carbamoyl phosphate metabolism. Biochemical assays showed that Salmonella enterica RidA and Rid2, but not Rid7, can hydrolyze imines generated by amino acid oxidase. Genetic tests indicated that carbamoyl phosphate overproduction is toxic to S. enterica cells lacking RidA, and metabolomic profiling of Rid knockout strains showed ten-fold accumulation of the carbamoyl phosphate-related metabolite dihydroorotate.ConclusionsLike the archetypal RidA subfamily, the Rid2, and probably the Rid1 and Rid3 subfamilies, have imine-hydrolyzing activity and can pre-empt damage from imines formed by amine oxidases as well as by pyridoxal 5'-phosphate enzymes. The RidA subfamily has an additional damage pre-emption role in carbamoyl phosphate metabolism that has yet to be biochemically defined. Finally, the Rid4 to Rid7 subfamilies appear not to hydrolyze imines and thus remain mysterious

Phenylketonuria in South Africa - A report on the status quo

During the 1980s a pilot newborn screening programme for the early detection (and treatment) of amino acidopathies, especially phenylketonuria (PKU), was conducted by the Department of National Health and Population Development. The motivation for this pilot programme was the high priority accorded PKU screening in Europe and North America and the presumed similarly high incidence of this condition among South Africans of European origin. From a cohort of 59 600 newborns screened in the Pretoria area over a period of 8 consecutive years (1979 - 1986), only 1 case of PKU (and 1 of tyrosinaemia) was found. Statistically this result is compatible (Poisson distribution, 95% confidence interval) with a 'true' incidence of not more than 3/59 600 (or about 1/20000) newborns. It is concluded from this result and other relevant information that newborn screening for PKU and other amino acidopathies is not cost-effective and justifiable, especially against the background of prevailing demographic conditions and more pressing health priorities in South Africa. This particular screening programme was discontinued in 1986. The results and conclusions are presented here. for the record

Improved Enzymatic Method for Determining Mannitol and its Application to Dog Serum after Mannitol Infusion

Peer Reviewe

Baclofen Toxicity Causing Acute, Reversible Dyskinesia.

The following unique case demonstrates an episode of acute dyskinesia secondary to oral baclofen toxicity. We discuss an 80-year-old man with a history of Stage III chronic kidney disease, coronary artery disease, diabetes and stroke who presented to the Emergency Department with new onset of behavioral changes and irregular jerking movements. The patient had been recently prescribed baclofen 10mg twice daily for a back strain he suffered; he subsequently was admitted to the hospital, and his symptoms resolved within 48 hours of admission and discontinuance of baclofen

A semi-classical over-barrier model for charge exchange between highly charged ions and one-optical electron atoms

Absolute total cross sections for electron capture between slow, highly charged ions and alkali targets have been recently measured. It is found that these cross sections follow a scaling law with the projectile charge which is different from the one previously proposed basing on a classical over-barrier model (OBM) and verified using rare gases and molecules as targets. In this paper we develop a "semi-classical" (i.e. including some quantal features) OBM attempting to recover experimental results. The method is then applied to ion-hydrogen collisions and compared with the result of a sophisticated quantum-mechanical calculation. In the former case the accordance is very good, while in the latter one no so satisfactory results are found. A qualitative explanation for the discrepancies is attempted.Comment: RevTeX, uses epsf; 6 pages text + 3 EPS figures Journal of Physics B (scehduled March 2000). This revision corrects fig.

Polypeptides, Nucleic Acid Molecules, and Methods for Synthesis of Triterpenes

This application relates to the polypeptides, nucleic acid molecules, vectors, transfected cells, and methods for synthesis of triterpenes, including botryococcene

Method and System for Producing Triterpenes

A method and system are provided for the production of triterpene including methylated triterpenes. The method and system include isolated nucleic acid sequences encoding triterpene methyltransferases such as triterpene methyltransferases 1, 2, 3. Advantageously, the method and system includes transgenic plant cells via an expression vector for triterpene methyltransferase and optionally various triterpene synthase and prenyltransferase all with tags directing these enzymes to the chloroplast of the transgenic plant cells for using the chloroplast methyl erythritol phosphate (MEP) pathway in the triterpene biogenesis

How Safe is "Too" Safe?

Safety expenditures usually follow the law of diminishing returns, i.e. marginal cost of risk reduction increases progressively with the level of safety achieved. Though the risk of a facility can in principle be reduced below any given value it is not possible to reduce the risk to zero, to reach "absolute safety". This poses the question about the level at which further risk reduction is no longer cost-effective. This paper demonstrates that these considerations are only valid if a system element (e.g. a plant) is analyzed. When the total economic system is considered another source of risk has to be added: the occupational and public health effects associated with the production of safety equipment. Using some simplifying assumptions and data from national economic input-output tables and occupational accident statistics it is possible to derive a linear relationship between the cost of the safety equipment and the health effects caused by its production. When this relation is combined with the. exponential risk-cost relationship of the facility under consideration, the combined curve exhibits a minimum value where the health effects of producing the safety feature equals the health effects avoided when it is installed. It is shown that if one probable health effect at some unknown future, time is avoided by use of $30 million of safety equipments, one equivalent health effect will certainly occur at the present time. The problem of balancing these two effects is a societal decision which is not addressed herein