| Phenyl-2-aminoethylselenide (PAESe) and its derivatives are a novel class of compounds targeting the enzyme dopamine beta-monooxygenase (DMB, E.C. 1.14.17.1). DBM catalyzes the final step in the synthesis of the adrenergic neurotransmitter norepinephrine (NE). Norepinephrine modulates vascular tone and its levels contribute to the physiology of hypertension. PAESe and its derivatives have exhibited antihypertensive abilities in spontaneously hypertensive rats (SHR). It had been speculated that the therapeutic activity of these compounds was due to a relaxation of the vasculature. To test this hypothesis, pulsed Doppler ultrasound imaging is being used here to quantitate blood flow velocities, acceleration, and left ventricular ejection time from the aortic arch of SHR's and relate this to the physiological effect of the drug.;Exploring the uses of enzymes in synthetic methods is a novel approach to synthesize compounds previously made by multistep traditional chemical methods. Enzymes exhibit stereoselectivity and high catalytic rates under relatively mild conditions giving them advantages over non-enzymatic catalysis. Traditional enzymology is carried out in aqueous media, however in synthetic situations the use of water as a solvent is not always practical. Changes in regioselectivity, chemoselectivity, and stereoselectivity of enzymes have been observed when enzymes have been placed in low water systems. Using ureidoglycolate lyase (UGL, E.C. 4.3.2.3), a bacterial lyase that catalyzes a key step in the metabolism of purines, in organic media an investigation into these characteristics was undertaken.;Polyhydroxybutyrate (PHB) is a polymer if D-(-)-beta-hydroxybutyric acid, generated by various strains of bacteria in response to a variety of environmental conditions. PHB is of considerable interest as an alternative polymer based on its biodegradable properties. In vivo, the polymer is produced in a biosynthetic pathway involving three enzymes, beta-ketothiolase (E.C. 2.3.1.16), acetoacetyl CoA reductase (E.C. 1.1.1.36), and PHB synthase. Using purified forms of all three enzymes, the production of PHB in an in vitro system was undertaken. |
