EXAMINING THE EFFECT OF STEROL CARRIER PROTEIN-2 ON PHYTANIC ACID TOXICITY

Program year: 1997/1998Digitized from print original stored in HDRAlthough peroxisomes are essential organelles involved in the conversion of hydrogen peroxide to water, they also contain unique metabolic pathways in lipid metabolism. One of these is the a-oxidation of branched-chain fatty acids such as phytanic acid. Phytanic acid accumulates to toxic levels in patients with defective or deficient numbers of peroxisomes. Little is known about how phytanic acid is taken up into the cell and incorporated into the peroxisome. Sterol carrier protein-2 (SCP-2), a lipid-binding protein concentrated in peroxisomes, may function in phytanic acid uptake and metabolism. Fluorescence techniques have shown that SCP- 2 can bind phytanic acid, but it is not known whether SCP-2 enhances uptake and/or metabolism of phytanic acid in intact cells. SCP-2 is concentrated in the peroxisomes, but significant amounts are also on the mitochondria and cytosol. To examine SCP-2 function and location of function, transfected L-cells over-expressing SCP-2 were exposed to a phytanic acid-albumin complex or a palmitic acid-albumin complex, and their relative toxicities were compared. The data show that SCP-2 enhanced the toxicity of phytanic acid, which undergoes a-oxidation in the peroxisome, but not that of palmitic acid, which undergoes normal β-oxidation in the mitochondria. However, further study is needed to resolve the mechanism whereby SCP-2 mediates the toxicity 01 phytanic acid