Our study underscores the importance of thoroughly characterizing the genetic make up of unique populations when considering pharmacogenetic testing for individualized therapy.

Swayback disease, a neurodegenerative disorder of lambs, and Menkes disease, the human equivalent, are caused by a deficiency of dietary copper. Reports of low enzymic activity suggest that several copper-containing enzymes, including cytochrome-c oxidase (COX), may influence the progress of these diseases. To investigate its role in the development of neurodegenerative disorders, in particular swayback disease, we isolated COX from the brains and livers of swayback-diseased lambs. Comparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) combined with densitometric analysis revealed that whereas the structure of COX from the liver of diseased animals was normal, the corresponding brain enzyme was subunits II-, III-, and IV-deficient; the deficiency was 55, 30, and 65% respectively. The activities of liver and brain COX from normal and diseased lambs were compared by polarographic assay at low ionic strength. Whereas the enzyme from normal brains and both forms of the liver enzyme yielded characteristic biphasic Eadie-Hofstee plots, the brain enzyme from diseased animals displayed a single phase with a K(m) of 4.7 +/- 2.4 x 10(-6) M: the K(m) values of COX from the normal brain were 12 +/- 2.5 x 10(-6) and 5.5 +/- 0.5 x 10(-7) M. We conclude that the altered enzyme structure accounts for the uncharacteristic kinetics and low activity we have observed for the isolated brain enzyme. We also conclude that the altered enzyme structure partly accounts for the low oxidase activity and decreased ATP synthesis that has been widely reported for brain tissue from swayback-diseased animals. We postulate that the subunit deficiency probably results from incomplete crosslinking between the subunits and the membrane, and predict that similar structural and kinetic factors may also account for low COX activity in Menkes disease.

Die bisher unbekannten Verbindungen (I): BaCa2In6O12 und (II): BaSr2In6O12 wurden einkristallin dargestellt und die Kristallstrukturen aufgeklärt. (I) und (II) kristallisieren hexagonal, Raumgruppe C 6h2P63/m, mit(I): a = 9,880; c = 3,211 Å und (II): a = 9,9443; c = 3,2671 Å, Z = 1. Mit den metastabilen Kristallstrukturen von AM2Ln6O12 sind beide Stoffe isotyp, ohne selbst metastabil zu sein. Im [In6O12]6−‐Gerüst wird einer der Tunnel mit Ca2+‐ bzw. Sr2+‐Ionen besetzt. Ein zweiter Tunnel nimmt Ba2+ auf vier verschiedenen Plätzen in statistischer Verteilung auf. (I) und (II) belegen die Existenz des AM2Ln3O12‐Typs bei kleinen Ln3+‐Teilchen.

(I) Ba2SrIn2O6 und (II) Sr0,93Ba0,07In2O4 wurden einkristallin dargestellt und mit Röntgenmethoden untersucht. I kristallisiert tetragonal, Raumgruppe D 4h17 – I4/mmm, a = 4,168; c = 21,290 Å; Z = 2; II Raumgruppe D 2h16 – Pnma, a = 9,858; b = 3,273; c = 11,520 Å; Z = 4. I zeigt gegenüber der früher untersuchten Verbindungen BaSr2In2O6 eine unerwartete statistische Verteilung von Ba2+ und Sr2+ im La2SrCu2O6‐Typ. II markiert die Grenze des Existenzbereiches des Calciumferrat(III)‐Typs bei Erdalkalimetall‐Oxoindaten in Richtung großer M2+‐Ionenradien.

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