Irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by H2O2

A concentration-dependent inactivation of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase was found on reincubation of rat liver microsomal preparations with H2O2 and at lower concentrations in the presence of KCN which inhibited the contaminating catalase. The inactivation was not affected in the presence quenchers of hydroxyl radicals and singlet oxygen and was also obtained when H2O2 was added during the reaction. HMG-CoA, but not NADPH, partially protected the enzyme from H2O2-inactivation. Even at high concentration DTT was unable to reverse this inactivation. The soluble 50 kDa-enzyme was similarly inactivated by H2O2, and the tryptic-digest of the inactivated protein indicated the presence of a disulfide-containing peptide. The results support the view that H2O2 by directly acting on the catalytic domain possibly converts an active thiol group to an inaccessible disulfide and irreversibly HMG-CoA reductase.

Molecular structure of Lantadene-B&C, triterpenoids ofantana camara, red variety: Lantadene-B, 22β-angeloyloxy-3-oxoolean-12-en-28-oic acid; Lantadene-C, 22 β-(S)-2′-methyl butanoyloxy-3-oxoolean-12-en-28-oic acid

(I)Lantadene-B: C35H52O5,M r =552.80, MonoclinicC2,a=25.65(1),b=6.819(9),c=18.75(1) Å,beta=100.61(9),V=3223(5) Å3,Z=4,D x =1.14 g cm–3 CuKagr (lambda=1.5418A),mgr=5.5 cm–1,F(000)=1208,R=0.118,wR=0.132 for 1527 observed reflections withF o ge2sgr(F o ). (II)Lantadene-C: C35H54O5·CH3OH,Mr=586.85, Monoclinic,P21,a=9.822(3),b=10.909(3),c=16.120(8)Å,beta=99.82(4),V=1702(1)Å3,Z=2,D x =1.145 g cm–3, MoKagr (lambda=0.7107Å), mgr=0.708 cm–1 F(000)=644,R=0.098, wR=0.094 for 1073 observed reflections. The rings A, B, C, D, and E aretrans, trans, trans, cis fused and are in chair, chair, sofa, half-chair, chair conformations, respectively, in both the structures. In the unit cell the molecules are stabilized by O-HctdotO hydrogen bonds in both the structures, however an additional C-HctdotO interaction is observed in the case of Lantadene-C.

On the involvement of intramolecular protein disulfide in the irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by diallyl disulfide

Treatment with diallyl disulfide, a constituent of garlic oil, irreversibly inactivated microsomal and a soluble 50 kDa form of HMG-CoA reductase. No radioactivity was found to be protein-bound on treating the soluble enzyme with [35S]diallyl disulfide, indicating the absence of the mixed disulfide of the type allyl-S-S-protein. SDS-PAGE and Western blot analyses of the diallyl-disulfide-treated protein showed no traces of the dimer of the type protein-S-S-protein, but clearly indicated BME-reversible increased mobility, as expected of an intramolecular protein disulfide. The sulfhydryl groups, as measured by alkylation with iodo[2-14C]acetic acid, were found to decrease in the diallyl-disulfide-treated enzyme protein. Tryptic peptide analysis also gave support for the possible presence of disulfide-containing peptides in such a protein. It appears that diallyl disulfide inactivated HMG-CoA reductase by forming an internal protein disulfide that became inaccessible for reduction by DTT, and thereby retaining the inactive state of the enzyme.

Organometallic chemistry of diphosphazanes *1: VIII. Synthesis, spectroscopic studies and crystal structure of fac-[Mo(CO)3(MeCN)Ph2PN(iPr)P(Ph)(DMP)], and its reactions with tertiary phosphines

The reaction of fac-[Mo(CO)3(MeCN)3] with the unsymmetrical diphosphazane Ph2PN(iPr)P(Ph)(DMP) (L) gives the complex fac-[Mo(CO)3(MeCN)(L)] (2) in almost quantitative yield. The structure of the complex has been determined by an X-ray diffraction study. The compound reacts with PR3 (where R = Ph, OPh) to give fac-[Mo(CO)3(PR3)(L)] (3a, 4a), which undergoes an intramolecular isomerization to afford mer-[Mo(CO)3(PR3)(L)] (3b, 4b). Synthesis of cis-[Mo(CO)4(L)] (1) and fac-[MO(CO)3L] (2a) and their spectroscopic data are also reported.

Annales Societatis zoologicae-botanicae Fennicae Vanamo tom. 3

Kielet suomi ja saksa.

Insights into conformational and packing features in a series of aryl substituted ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

The supramolecular structures of eight aryl protected ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine- 5-carboxylates have been analyzed to determine the role of different functional groups on the molecular geometry, conformational characteristics and the packing of these molecules in the crystal lattice. Out of these the para fluoro substituted compound on the aryl ring exhibits conformational polymorphism, due to the different conformation of the ester moiety. This behaviour has been characterized using both powder and single-crystal X-ray diffraction, optical microscopy and differential scanning calorimetry performed on both these polymorphs. The compounds pack via the cooperative interplay of strong N-H center dot center dot center dot O=C intermolecular dimers and chains forming a sheet like structure. In addition, weak C-H center dot center dot center dot O=C and C-H center dot center dot center dot pi interactions impart additional stability to the crystal packing.

Microwave Irradiation Assisted Method for the Rapid Synthesis of fine Particles of alpha Al2O3 And alpha (Al1-XCrx)(2)O-3 And Their Coatings on Si(100)

Chromium substituted beta diketonate complexes of aluminium have been synthesized and employed as precursors for a novel soft chemistry process wherein microwave irradiation of a solution of the complex yields within minutes well crystallized needles of alpha (Al1 XCrx)(2)O-3 measuring 20 30 nm in diameter and 50 nm long By varying the microwave irradiation parameters and using a surfactant such as polyvinyl pyrrolidone the crystallite size and shape can be controlled and their agglomeration prevented These microstructural parameters as well as the polymorph of the Cr substituted Al2O3 formed may also be controlled by employing a different complex Samples of alpha (Al1 XCrx)(2)O-3 have been characterized by XRD FTIR and TEM The technique results in material of homogeneous metal composition, as shown by EDAX and can be adjusted as desired The technique has been extended to obtain coatings of alpha (Al1 XCrx)(2)O-3 on Si(100)