Distribution and metabolism of dolichol and dolichyl phosphate in rat liver.

Abstract

The dolichol and dolichyl phosphate (Dol-P) content of various tissues and liver subcellular fractions obtained from rats have been measured directly using high pressure liquid chromatographic methods developed in this laboratory. Spleen contained the highest concentration of dolichol, while other tissues including serum had smaller amounts. Although considerable differences in homologue distribution patterns were observed among the tissues examined, a number of purified subcellular fractions obtained from liver (nuclei, mitochondria, cytosol, and microsomes) exhibited a single common pattern. Only some 5% of liver dolichol appeared in the microsomal compartment of the cell where glycoprotein formation occurs, while 50% of the dolichol in this tissue was found in a lysosome-enriched fraction. The concentrations of dolichol present in liver nuclei, mitochondria, whole microsomes (also rough and smooth, endoplasmic recticulum (RER and SER, respectively), and cytosol were considerably lower (on a protein basis) than those present in whole liver. Besides the lysosome-enriched fraction, only plasma membranes and Golgi contained dolichol at concentrations equal to or greater than those present in liver homogenates. The low concentrations of dolichol found in microsomes suggest that the amounts of dolichol available for Dol-P formation via the CTP-dependent kinase reaction may be rate limiting. Most of the Dol-P in liver could be recovered in the microsomal fraction. Dol-P accounted for 4 and 40% of the sum of alcohol + dolichyl fatty acyl ester + Dol-P forms present in whole liver and in microsomes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)