Kinetic and pH Studies on Human Phenylethanolamine N-Methyltransferase

Phenylethanolamine N-methyltransferase (PNMT) catalyzes the conversion of norepinephrine (noradrenaline) to epinephrine (adrenaline) while, concomitantly, S-adenosyl-l-methionine (AdoMet) is converted to S-adenosyl-l-homocysteine. This reaction represents the terminal step in catecholamine biosynthesis and inhibitors of PNMT have been investigated, inter alia, as potential antihypertensive agents. At various times the kinetic mechanism of PNMT has been reported to operate by a random mechanism, an ordered mechanism in which norepinephrine binds first, and an ordered mechanism in which AdoMet binds first. Here we report the results of initial velocity studies on human PNMT in the absence and presence of product and dead end inhibitors. These, coupled with isothermal titration calorimetry and fluorescence binding experiments, clearly shown that hPNMT operates by an ordered sequential mechanism in which AdoMet binds first. Although the log V pH-profile was not well defined, plots of log V/K versus pH for AdoMet and phenylethanolamine, as well as the pKi versus pH for the inhibitor, SK&F 29661, were all bell-shaped indicating that a protonated and an unprotonated group are required for catalysis

The role of controllability in optimizing quantum dynamics

This paper discusses the important role of controllability played on the complexity of optimizing quantum mechanical control systems. The study is based on a topology analysis of the corresponding quantum control landscape, which is referred to as the optimization objective as a functional of control fields. We find that the degree of controllability is closely relevant with the ruggedness of the landscape, which determines the search efficiency for global optima. This effect is demonstrated via the gate fidelity control landscape of a system whose controllability is restricted on a SU(2) dynamic symmetry group. We show that multiple local false traps (i.e., non-global suboptima) exist even if the target gate is realizable and that the number of these traps is increased by the loss of controllability, while the controllable systems are always devoid of false traps.Comment: 13 pages, 3 figure

Hot Jupiters in binary star systems

Radial velocity surveys find Jupiter mass planets with semi-major axes a less than 0.1 AU around ~1% of solar-type stars; counting planets with $a$ as large as 5 AU, the fraction of stars having planets reaches ~ 10% {Marcy,Butler}. An examination of the distribution of semi-major axes shows that there is a clear excess of planets with orbital periods around 3 or 4 days, corresponding to a~0.03$ AU, with a sharp cutoff at shorter periods (see Figure 1). It is believed that Jupiter mass planets form at large distances from their parent stars; some fraction then migrate in to produce the short period objects. We argue that a significant fraction of the `hot Jupiters' (a<0.1 AU) may arise in binary star systems in which the orbit of the binary is highly inclined to the orbit of the planet. Mutual torques between the two orbits drive down the minimum separation or periapse r_p between the planet and its host star (the Kozai mechanism). This periapse collapse is halted when tidal friction on the planet circularizes the orbit faster than Kozai torque can excite it. The same friction then circularizes the planet orbit, producing hot Jupiters with the peak of the semimajor axis distribution lying around 3 days. For the observed distributions of binary separation, eccentricity and mass ratio, roughly 2.5% of planets with initial semimajor axis a_p ~ 5au will migrate to within 0.1au of their parent star. Kozai migration could account for 10% or more of the observed hot Jupiters.Comment: accepted to ApJ main journal, added one figure and expanded discussion

The equilibrium model for the effect of temperature on enzymes: Insights and implications

A new, experimentally-validated “Equilibrium Model” describes the effect of temperature on enzymes, and provides a new mechanism for the reversible loss of enzyme activity with temperature. It incorporates two new, fundamental parameters that allow a complete description of the effect of temperature on enzyme activity: ΔHeq and Teq. ΔHeq emerges as an intrinsic and quantitative measure of enzyme eurythermal adaptation, while Teq, the equilibrium temperature, has fundamental and technological significance for our understanding of the effect of temperature on enzymatic reactions. For biotechnological purposes, these parameters need to be considered when enzymes are applied or engineered for activity at high temperatures