2006 - Institut für Klinische Chemie - UniversitätsSpital Zürich
2006 - Institut für Klinische Chemie - UniversitätsSpital Zürich
2006 - Institut für Klinische Chemie - UniversitätsSpital Zürich
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Universität <strong>Zürich</strong> > Medizinische Fakultät > <strong>Klinische</strong> <strong>Chemie</strong>, <strong>Institut</strong> <strong>für</strong> > Prof. Dr.<br />
Arnold von Eckardstein<br />
Sphingolipid metabolism<br />
Summary / Zusammenfassung<br />
Sphingolipids are a ubiquitously distributed class of lipids that confer important structural<br />
properties to membranes and to their partition into microdomains (`membrane rafts`), and<br />
modulate the activities of various enzymes such as protein kinases, protein phosphatases and<br />
phospholipases in cells or cell-free systems. They participate in many cellular events including<br />
proliferation, differentiation, senescence, apoptosis and inflammatory responses. De novo<br />
sphingolipid biosynthesis is initiated by the condensation of L-serine with palmitoyl-CoA to<br />
generate 3-ketodihydrosphingosine. This pyridoxal-5-phosphate (PLP) dependant reaction is<br />
catalyzed by the serine-palmitoyltransferase (SPT; EC2.3.1.50). The structure, function and<br />
regulation of this key enzyme are little understood. SPT has been reported to be a heterodimer<br />
composed of two subunits - SPTLC1 and SPTLC2. We found that the native SPT complex rather<br />
is a high molecular weight complex of 700-800kD and composed of three subunits - namely<br />
SPTLC1, SPTLC2, a newly identified subunit SPTLC3. In addition we identified novel splice<br />
variants of SPTLC1 and SPTLC2. Currently we are trying to unravel the function and regulation of<br />
the three SPT isoenzymes and their splice variants and establish essays to investigate any clinical<br />
relevance of SPT activity.<br />
Publications / Publikationen<br />
Hornemann T, Richard S, Rütti MF, Wei Y, von Eckardstein A (<strong>2006</strong>). Cloning and initial<br />
characterization of a new subunit for mammalian serine-palmitoyltransferase. J. Biol. Chem. 281<br />
(49):37275-81.<br />
Hornemann T, Wei Y, von Eckardstein A (2007). Is the Serine-Palmitoyltransferase a high<br />
molecular weight complex? Biochem. J. in press<br />
Keywords / Suchbegriffe<br />
lipid metabolism, peripheral neuropathy, sphingomyelin, ceramide, serin palmitoyl transferase<br />
Project Leadership and Contacts / Projektleitung und Kontakte<br />
Dr. Thorsten Hornemann (Project Leader) thorsten.hornemann@usz.ch<br />
Prof. Arnold von Eckardstein (Project Leader) arnold.voneckardstein@usz.ch<br />
Funding Source(s) / Unterstützt durch<br />
Foundation, No project-specific funding<br />
Stiftung <strong>für</strong> wissenschaftliche Forschung an der Universität <strong>Zürich</strong>Hartmann Müller - Stiftung <strong>für</strong><br />
medizinische Forschung<br />
In Collaboration with / In Zusammenarbeit mit<br />
Prof. Ueli Suter, ICB, ETHZ<br />
Prof. Theo Wallimann, ICB, ETHZ<br />
Project 3271<br />
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