Disposition of morphine in man

The disposition of morphine was investigated by means of radioimmunoassay after a single intravenous dose (10 milligrams per 70 kilograms) was administered to 10 adult normal male subjects who had not received other drugs for 2 weeks preceding the study. A multiphasic decline in serum concentrations of morphine occurred. Detectable blood concentrations of morphine, or of a metabolite, or of both persisted for 48 hours after a single intravenous dose.     

Biosynthesis of the morphine alkaloids

Tracer experiments, supported throughout by the analogous chemical transformations, have firmly established the biosynthetic sequence tyrosine -->norlaudanosoline --> reticuline --> salutaridine --> salutaridinol-I -->thebaine --> codeine --> morphine in Papaver somniferum. In general, the farther a precursor lies along this sequence, the more efficient its conversion to morphine in the intact plant. Several intermediates remain to be discovered, such as those lying between tyrosine and norlaudanosoline and between thebaine and codeine. Proof that morphine is made only by the reticuline-salutaridine route is still lacking and would require a careful comparison of the rate of morphine synthesis with the turnover rates for the various intermediates. More importantly, detailed knowledge of the mechanism of each biochemical step can come only with isolation of the enzyme system involved. The chemical oxidation of (-)-reticuline, to give salutaridine, can only be accomplished in very low (0.02 percent) yield (15, 26), whereas, even with whole plants, the biological incorporation of reticuline into the morphine alkaloids can reach 8 percent (13). One would like to know just how an enzyme system directs the oxidative cyclization of reticuline in the desired sense. Kleinschmidt and Mothes and Fairbairn and Wassel (27) have shown that the latex isolated from opium poppies is capable of transforming tyrosine into morphine. Perhaps further work with opium latex will provide the key to the remaining problems of morphine biosynthesis.     

Neuroanatomical correlates of morphine dependence

Naloxone hydrochloride, an opioid antagonist, was applied to several discrete brain regions of morphine-dependent rats to precipitate abstinence. Severe withdrawal signs were elicited after administration in the thalamus but not in neocortical, hippocampal, hypothalamic, or tegmental areas of the brain.     

The structure of abelsonite

Abelsonite, a C(31) nickel-porphyrin of the deoxophylloerythroetioporphyrin type, is shown to have methyl groups in the 2, 3, 7, 12, and 18 positions and ethyl groups in the 8 and 17 positions by high-resolution, high-field (1)H nuclear magnetic resonance and nuclear Overhauser effect studies. Removal of the nickel by treatment with methanesulfonic acid permitted confirmation of the structure on the free base porphyrin and demonstrated structural integrity under the conditions required for demetallation. The structure is best accounted for geochemically by the hypothesis that abelsonite is derived from a chlorophyll.     

The structure of arthropod hemocyanins

Hemocyanins are large multi-subunit copper proteins that transport oxygen in many arthropods and molluscs. Comparison of the amino acid sequence data for seven different subunits of arthropod hemocyanins from crustaceans and chelicerates shows many highly conserved residues and extensive regions of near identity. This correspondence can be matched closely with the three domain structure established by x-ray crystallography for spiny lobster hemocyanin. The degree of identity is particularly striking in the second domain of the subunit that contains the six histidines which ligate the two oxygen-binding copper atoms. The polypeptide architecture of spiny lobster hemocyanin appears to be the same in all arthropods. This structure must therefore be at least as old as the estimated time of divergence of crustaceans and chelicerates, about 540 to 600 million years ago.     

The zeolite cage structure

Zeolites are typically aluminosilicates whose framework structures have pores of molecular dimensions. They are widely used as ion exchangers and sorbents and in hydrocarbons conversion catalysis and separations. Recent zeolite research has focused on widening the scope of synthetic procedures, on further exploiting zeolites in commercial processes, and on applying modern characterization techniques to unraveling the complexities of zeolite structural properties.     

Cellular adaptation to morphine in rats

The respiration of KCl-stimulated cortical slices of brain from control rats is markedly depressed by morphine, whereas the respiration of those from rats chronically dosed with morphine is unaffected. The results demonstrate an adaptation to morphine at the cellular level which is concomitant with the adaptation of the whole animal to morphine     

The local structure of amorphous silicon

It is widely believed that the continuous random network (CRN) model represents the structural topology of amorphous silicon. The key evidence is that the model can reproduce well experimental reduced density functions (RDFs) obtained by diffraction. By using a combination of electron diffraction and fluctuation electron microscopy (FEM) variance data as experimental constraints in a structural relaxation procedure, we show that the CRN is not unique in matching the experimental RDF. We find that inhomogeneous paracrystalline structures containing local cubic ordering at the 10 to 20 angstrom length scale are also fully consistent with the RDF data. Crucially, they also matched the FEM variance data, unlike the CRN model. The paracrystalline model has implications for understanding phase transformation processes in various materials that extend beyond amorphous silicon.     

The structure of human 5-lipoxygenase

The synthesis of both proinflammatory leukotrienes and anti-inflammatory lipoxins requires the enzyme 5-lipoxygenase (5-LOX). 5-LOX activity is short-lived, apparently in part because of an intrinsic instability of the enzyme. We identified a 5-LOX-specific destabilizing sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron. Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence.     

The structure of a retinal-forming carotenoid oxygenase

Enzymes that produce retinal and related apocarotenoids constitute a sequence- and thus structure-related family, a member of which was analyzed by x-ray diffraction. This member is an oxygenase and contains an Fe2+-4-His arrangement at the axis of a seven-bladed beta-propeller chain fold covered by a dome formed by six large loops. The Fe2+ is accessible through a long nonpolar tunnel that holds a carotenoid derivative in one of the crystals. On binding, three consecutive double bonds of this carotenoid changed from a straight all-trans to a cranked cis-trans-cis conformation. The remaining trans bond is located at the dioxygen-ligated Fe2+ and cleaved by oxygen.