Sulfur-substituted and alpha-methylated fatty acids as peroxisome proliferator-activated receptor activators.

FA with varying chain lengths and an alpha-methyl group and/or a sulfur in the beta-position were tested as peroxisome proliferator-activated receptor (PPAR)alpha, -delta(beta), and -gamma ligands by transient transfection in COS-1 cells using chimeric receptor expression plasmids, containing cDNAs encoding the ligand-binding domain of PPARalpha, -delta, and -gamma. For PPARalpha, an increasing activation was found with increasing chain length of the sulfur-substituted FA up to C14-S acetic acid (tetradecylthioacetic acid = TTA). The derivatives were poor, and nonsignificant, activators of PPARdelta. For PPARgamma, activation increased with increasing chain length up to C16-S acetic acid. A methyl group was introduced in the alpha-position of palmitic acid, TTA, EPA, DHA, cis9,trans11 CLA, and trans10,cis12 CLA. An increased activation of PPARalpha was obtained for the alpha-methyl derivatives compared with the unmethylated FA. This increase also resulted in increased expression of the two PPARalpha target genes acyl-CoA oxidase and liver FA-binding protein for alpha-methyl TTA, alpha-methyl EPA, and alpha-methyl DHA. Decreased or altered metabolism of these derivatives in the cells cannot be excluded. In conclusion, saturated FA with sulfur in the beta-position and increasing carbon chain length from C9-S acetic acid to C14-S acetic acid have increasing effects as activators of PPARalpha and -gamma in transfection assays. Furthermore, alpha-methyl FA derivatives of a saturated natural FA (palmitic acid), a sulfur-substituted FA (TTA), and PUFA (EPA, DHA, c9,t11 CLA, and t10,c12 CLA) are stronger PPARalpha activators than the unmethylated compounds.

[Lorentz Eldjarn--a catalyst for chemistry in Norwegian medicine]. / Lorentz Eldjarn--ein katalysator for kjemi i norsk medisin.

Lorentz Eldjarn, MD (born 1920) was professor of clinical biochemistry at the University of Oslo. He modernised clinical chemistry both nationally and internationally. He introduced both quality control and mass spectrometry in clinical chemistry. In the 1950s he studied the radioprotective compound cystamine and showed that it forms mixed disulfides with protein SH groups. In part, this explains its radioprotective effect. In 1961, he founded the Department of Clinical Biochemistry at the University of Oslo, where most of the Norwegian clinical chemists were trained in the following years. His introduction of mass spectrometry as an analytical tool in clinical chemistry led to the detection of three new errors of metabolism in his institute: methylmalonic aciduria, beta-hydroxyisovaleric aciduria, and pyroglutamic aciduria. In 1975, he was awarded the "Distinguished Clinical Chemist Award" of the International Association of Clinical Chemists, and in 1976 the Scandinavian Jahre research prize. After he resigned from his university position in 1978, he has continued his work to develop stable standard sera for clinical chemistry.