University of Stockholm

Partner 4: SU

Team Leader: Gustav Dallner, PhD (University of Stockholm)

Team Members:

  • Jerker Olsson, MD (Huddinge Hospital, University of Stockholm)
  • Kerstin Brismar, MD (Karolinska Medical Hospital)
  • Jacob Grunler, MD (Karolinska Medical Hospital)
  • Eva Swiezewska, PhD (Institute of Biochemistry and Biophysisc, Polland Academy of Sciences)
  • Tadeusz Chojnacki, PhD (Institute of Biochemistry and Biophysisc, Polland Academy of Sciences)

The group in Stockholm is working with the biosynthesis, metabolism and the enzymatic reduction of CoQ in human and experimental systems. They published new methods for synthesis of biosynthetic intermediates, new HPLC methods for isolation and identification of metabolic products, characterized several enzymes participating in the biosynthesis and studied the CoQ function in humans and in primary cultures.

The genetically characterized cells from patients incubated with labeled precursors and the enzymes with inappropriate catalytic activity are studied and identified with chromatography and fluorometrically (Dallner). In order to give final proof for the deficiency, the substrate for the reaction has to be chemically synthesized and the appearing products identified with mass spectrometry and NMR (Swiezewska).

A defect can be apparent not mainly because of the lack of CoQ but because of the low rate of cellular capacity to regenerate CoQ for antioxidant action by reducing enzymes (Olsson). Depending on the type and degree of deficiency, cells display various types of abnormalities concerning expression of signaling molecules and adhesion factors which is analyzed in detail with flow cytometry (Brismar). The CoQ deficiency caused by the low rate of synthesis is corrected by incubating the cells with CoQ. Recently, labeled CoQ was successfully synthesized, with labeling which remains after metabolic degradation (Chojnacki). Utilizing the labeled CoQ there is a unique possibility to establish how this lipid is distributed in the cell, which is the mechanism of the functional recovery, which metabolic modifications take place and how metabolites produced influence cellular activities (Grünler).

The scientists above are well established experts of their own field and previously closely cooperated in several projects. The Stockholm group is coordinated by Prof. Gustav Dallner at the Department of Biochemistry and Biophysics, Stockholm University. During the last ten years he is investigating the structure, biosynthesis and metabolic function of CoQ.

Assoc. Prof. Jerker Olsson at the Department of Pathology, Huddinge University Hospital, Stockholm has a long record on studies of the polyisoprenoid lipid biosynthesis and turnover in experimental and human cancer.

Dr Olsson has a laboratory with an up to date equipment park, also serving as core facility for the clinical research.

Prof. Kerstin Brismar is an expert of IGF and IGF-binding proteins and an authority in cellular signaling involving integrins and interleukins.

The group of Dr Jacob Grünler performed during many years extensive investigations on isolation and chemical analysis of cellular membranes and developed HPLC procedures for isolation of CoQ metabolites.

The groups of Prof. Ewa Swiezewska and Prof. Tadeusz Chojnacki at the Institute of Biochemistry and Biophysics, Polish Academy of Sciences are well known investigators of the scientific world and often visiting and working with the coordinating group in Stockholm. They are performing advanced organic synthesis of unlabelled and labeled intermediates and substrates of the mevalonate pathway and also intermediates of CoQ biosynthesis.

Among the above-mentioned senior investigators 7 are men and 7 are woman.

Gustav Dallner gustav@dbb.su.se

 
Ubigenes :: Genetics of coenzyme Q deficiency in humans