P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis

Studies of cancer metabolism have focused on the production of energy and the interconversion of carbons between cell cycles. More recently, amino acid metabolism, especially non-essential amino acids (NEAAs), has been investigated, underlining their regulatory role. One of the important mediators in energy production and interconversion of carbons in the cell is Δ1-pyrroline-5-carboxylate (P5C)—the physiological intracellular intermediate of the interconversion of proline, ornithine, and glutamate. As a central component of these conversions, it links the tricarboxylic acid cycle (TCA), urea cycle (UC), and proline cycle (PC). P5C has a cyclic structure containing a tertiary nitrogen atom (N) and is in tautomeric equilibrium with the open-chain form of L-glutamate-γ-semialdehyde (GSAL). P5C is produced by P5C synthase (P5CS) from glutamate, and ornithine via ornithine δ-amino acid transferase (δOAT). It can also be converted to glutamate by P5C dehydrogenase (P5CDH). P5C is both a direct precursor of proline and a product of its degradation. The conversion of P5C to proline is catalyzed by P5C reductase (PYCR), while proline to P5C by proline dehydrogenase/oxidase (PRODH/POX). P5C-proline-P5C interconversion forms a functional redox couple. Their transformations are accompanied by the transfer of a reducing-oxidizing potential, that affect the NADP+/NADPH ratio and a wide variety of processes, e.g., the synthesis of phosphoribosyl pyrophosphate (PRPP), and purine ribonucleotides, which are crucial for DNA synthesis. This review focuses on the metabolism of P5C in the cell as an interconversion mediator of proline, glutamate, and ornithine and its role in the regulation of survival and death with particular emphasis on the metabolic context.

Lead thiolates. The formation of water-soluble lead(II) thiolates and the crystal structure of 2-(Morpholin-4-yl)ethanethiolatolead(II) nitrate

The solubilized thiolate ligand 2-(morpholin-4-yl)ethanethiolate, mes, and its ammonium conjugate acid, Hmes, form crystalline complexes Pb2(Hmes)3(N03)4, Pb(mes)2, Pb(mes)(N03), Pb(mes)- (O2CCH3) and Pb(mes)(O2CCF3). These lead(II) thiolate complexes are soluble in aqueous media. Crystals of Pb(mes)(NO3) contain chains of alternating lead and bridging thiolate sulfur atoms [Pb-S 2.646(4), 2.793(4) �], with the lead coordinated also by the tertiary nitrogen atom [Pb-N 2.61(1) �]. The nitrate ions weakly bridge lead atoms along the chain [Pb-O 2.69(2), 2.88(2), 2.98(2), 3.03(2) �]. Crystal data: Pbca, a l3.396(2), b 21.900(3), c 7.348(1) �, Z 8(x PbSN2O4- C6H12), 1602 observed data, R 0.057.

The Crystal and Molecular Structure of the Antihistaminic Drug Triprolidine Hydrochloride Monohydrate [trans-1-(p-Tolyl)-1-(2-pyridyl)-3-(1-pyrrolidino)-prop-1-ene]

The title compound crystallizes from anisole with 4 molecules per unit cell. The space group of this cell is P21/c and the cell parameters are a = 14.777(2) Å, b = 9.5785(8) Å, c = 13.099(1) Å, and β = 90.48(2)°. Diffractometer data with CuKα radiation to 2θ = 129° were collected and the structure solved and refined to weighted and unweighted R factors of 0.077 and 0.051 respectively. The 2-pyridyl ring and the p-tolyl system make dihedral angles of 29.7 and 55.3° respectively with the plane of the double bond. The inter-aryl dihedral angle is 106.5°. The protonated tertiary nitrogen atom is hydrogen bonded to the chloride ion and two chloride ions are connected via hydrogen bonds in a distorted square planar arrangement by two water molecules. The pyridyl ring is involved in a π orbital overlap linkage with another pyridyl ring on the same side of the molecule as is the hydrogen bond from the nitrogen function. Brief characteristics of a flexible receptor protein which will bind antihistamine drugs are given.

The fluorescence of indoles and aniline derivatives

1. The variations in the excitation and fluorescence wavelengths and fluorescence intensities of a number of indole and aniline derivatives over a wide range of acidity and alkalinity (36n-sulphuric acid to 10n-potassium hydroxide) have been studied. 2. The changes in fluorescence with pH of the indoles and anilines had many characteristics in common, and the most fluorescent species were found to be the non-ionized or neutral forms showing fluorescence maxima at about λ 350mμ. 3. In 10n-potassium hydroxide most of the compounds examined, except those containing a tertiary nitrogen atom, showed a bathochromic shift in fluorescence wavelength attributable to an anion due to a negatively charged nitrogen, but in strong acid (3n-sulphuric acid) these compounds were non-fluorescent, except the anisidines and the 5-hydroxyindoles. 4. p-Anisidine but not the o- and m-isomers showed excited-state ionization in acid solution. 5. Of the hydroxyindoles only the 5-hydroxy derivatives showed a fluorescence (λmax. 520–540mμ) in acid solution. It is suggested that this fluorescence is due to a proton-transfer reaction in the excited state, and various arguments for this suggestion are given. 6. Stokes shifts for the various ionic and neutral species of the indoles and anilines have been calculated, and the large shifts found with indole and p-anisidine may be due to solvent–solute interaction.

LYCOPODIUM ALKALOIDS: XVI. ANNOTINE

Annotine, C16H21O3N, is shown to be pentacyclic and to contain a tertiary hydroxyl group, a lactone function, a tertiary nitrogen atom, and a dialkylated double bond. The position of the double bond and the tertiary hydroxyl group relative to the nitrogen atom has been established by Emde degradation of annotine methiodide. The presence of a lactone function is inferred from the reduction of annotine to dihydroannotinol, a hemiacetal, which reacts with 1 mole of ethyl mercaptan. The reduction of the lactone to a diol in an annotine derivative has been carried out. The chemical studies and the examination of annotine and its derivatives by modern instrumental methods allow the assignment of a plausible structure to the alkaloid.