Biosynthesis of plant sterols. Conversion of cholesterol to pregnenolone inDigitalis purpurea

Résumé Un échantillon purifié de cholestérol-4-C¹⁴ a été absorbé par des feuilles de 2 plantes deDigitalis purpurea. Après 18 jours on a extrait les plantes et séparé les composés radioactifs. Environ 1% des métabolites globales a été constaté en forme de pregnénolone. Ainsi le cholestérol peut agir comme précurseur des stérols végétaux.

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This work was supported by Grants No. CA-07137, No. A-5326 and No. FR-05528 from the U.S. Public Health Service, and No. G-21799 from the National Science Foundation.     

Biosynthesis of plant sterols. Conversion of cholesterol to pregnenolone in Digitalis purpurea

Zusammenfassung Der bei der Bestrahlung mit ionisierenden Strahlen auftretende Sättigungseffekt, d.h. die Abweichung von der Linearität des Verhältnisses zwischen der Strahlendosis und der Zahl der geschädigten Molekeln bei höheren Dosisleistungen, wird unter Zugrundelegung eines einfachen Modells, welches sowohl die Erzeugung als auch die Rekombination der Strahlenschäden berücksichtigt, mathematisch beschrieben.     

Ras, PI(3)K and mTOR signalling controls tumour cell growth

All eukaryotic cells coordinate cell growth with the availability of nutrients in their environment. The mTOR protein kinase has emerged as a critical growth-control node, receiving stimulatory signals from Ras and phosphatidylinositol-3-OH kinase (PI(3)K) downstream from growth factors, as well as nutrient inputs in the form of amino-acid, glucose and oxygen availability. Notably, components of the Ras and PI(3)K signalling pathways are mutated in most human cancers. The preponderance of mutations in these interconnected pathways suggests that the loss of growth-control checkpoints and promotion of cell survival in nutrient-limited conditions may be an obligate event in tumorigenesis.     

The proteasome antechamber maintains substrates in an unfolded state

Eukaryotes and archaea use a protease called the proteasome that has an integral role in maintaining cellular function through the selective degradation of proteins. Proteolysis occurs in a barrel-shaped 20S core particle, which in Thermoplasma acidophilum is built from four stacked homoheptameric rings of subunits, α and β, arranged α(7)β(7)β(7)α(7) (ref. 5). These rings form three interconnected cavities, including a pair of antechambers (formed by α(7)β(7)) through which substrates are passed before degradation and a catalytic chamber (β(7)β(7)) where the peptide-bond hydrolysis reaction occurs. Although it is clear that substrates must be unfolded to enter through narrow, gated passageways (13?? in diameter) located on the α-rings, the structural and dynamical properties of substrates inside the proteasome antechamber remain unclear. Confinement in the antechamber might be expected to promote folding and thus impede proteolysis. Here we investigate the folding, stability and dynamics of three small protein substrates in the antechamber by methyl transverse-relaxation-optimized NMR spectroscopy. We show that these substrates interact actively with the antechamber walls and have drastically altered kinetic and equilibrium properties that maintain them in unstructured states so as to be accessible for hydrolysis.