Hydrolysis of aminoacetonitrile: Peptide formation

Zusammenfassung Neutrale oder alkalische Hydrolyse von Aminoacetonitril gibt mindestens 6-Aminosäuren neben Glycin, welches das einzige Produkt bei saurer Hydrolyse ist. Die anderen-Aminosäuren entstehen durch die Hydrolyse der peptidähnlichen Polymere, welche durch die Polymerisierung des aus dem Aminoacetonitril gebildeten Cyanwasserstoffes mit basischen Katalysatoren gebildet werden. Im Zusammenhang mit der chemischen Evolutionstheorie weisen diese Resultate darauf hin, dass-Aminonitrile nur eine kleine oder gar keine direkte Rolle in der Aufeinanderfolge der Reaktionen gespielt haben, welche zur vorbiologischen Synthese von Polypeptiden und Proteinen führten.     

The effect of pancreozymin and acetylcholine on the membrane potential of the pancreatic acinar cells

Zusammenfassung Acetylcholin und Pancreozymin induzieren beide eine Depolarisation der Azinuszellmembran in der Bauchspeicheldrüse. Nur die Wirkung von Acetylcholin wird von Atropin blockiert. Das Ruhepotential kann auch durch eine erhöhte Kaliumkonzentration im Extrazellularraum reduziert werden, diese Wirkung wird nicht von Atropin beeinflusst. Die Acetylcholin-induzierte Depolarisation ist nicht von extrazellularer Kalziumkonzentration abhängig, sondern ist wahrscheinlich eine notwendige Bedingung für den Sekretionsprozess.

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Supported by grants from The Carlsberg Foundation, The Wellcome Trust and I. and H. Weismann's legat. Present address: Inst. Med. Physiol. C, Univ. Copenhagen, Denmark.

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Cholecystokinin-Pancreozymin was kindly provided by GIH research unit, Chemistry Department, Karolinska Institutet, Stockholm.     

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 × 10(-8) to P = 1.9 × 10(-11)). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 10(-4)), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.     

A mutant T4 lysozyme displays five different crystal conformations

Phage T4 lysozyme consists of two domains between which is formed the active-site cleft of the enzyme. The crystallographically determined thermal displacement parameters for the protein suggested that the amino terminal of the two domains undergoes 'hinge-bending' motion about an axis passing through the waist of the molecule. Such conformational mobility may be important in allowing access of substrates to the active site of the enzyme. We report here a crystallographic study of a mutant T4 lysozyme which demonstrates further the conformational flexibility of the protein. A mutant form of the enzyme with a methionine residue (Met 6) replaced by isoleucine crystallizes with four independent molecules in the crystal lattice. These four molecules have distinctly different conformations. The mutant protein can also crystallize in standard form with a structure very similar to the wild-type protein. Thus the mutant protein can adopt five different crystal conformations. The isoleucine for methionine substitution at the intersection of the two domains of T4 lysozyme apparently enhances the hinge-bending motion presumed to occur in the wild-type protein, without significantly affecting the catalytic activity or thermal stability of the protein.