IN-VIVO MEASUREMENT OF FATTY-ACIDS AND CHOLESTEROL-SYNTHESIS USING D2O AND MASS ISOTOPOMER ANALYSIS

The synthesis of palmitate, stearate, and cholesterol in liver and ner vous tissues (brain, cord, and nerve) of Sprague-Dawley rats was deter mined using deuterated water (D2O) and mass isotopomer analysis. Rats were given 4% deuterium in their drinking water after each receiving a n intraperitoneal priming dose. Animals were killed at 1, 2, 4, and 8 wk for deuterium enrichment in body water and determination of mass is otopomer distribution in lipids from various tissues. In 1 wk, the enr ichment in the body water reached a plateau of 2.6%, which is 65% of t hat in the drinking water. We observed the maximum incorporation numbe r (N) in all lipids to be higher than those previously observed, being 22, 24, and 30 for liver palmitate, stearate, and cholesterol, respec tively, and N may vary among tissues. Using a single exponential model , we found the half-time (t(1/2)) and the plateau levels of the newly synthesized lipids of the nervous tissues (t(1/2) values ranging from 5 to 28 days) to be different from those of the liver (t(1/2) values l ess than or equal to 4 days) in this relatively long-term study. Mass isotopomer distribution analysis and D2O can be used not only to quant itate the replacement rate of many lipids in various compartments but may also be used to elucidate the tissue-specific synthetic pathways f rom N.