COMPARISON OF SERINE AND HIPPURATE AS PRECURSOR EQUIVALENTS DURING INFUSION OF [N-15]GLYCINE FOR MEASUREMENT OF FRACTIONAL SYNTHETIC RATES OF APOLIPOPROTEIN-B OF VERY-LOW-DENSITY LIPOPROTEIN

Enrichment in hippurate has been measured to indicate precursor enrich ment during glycine tracer infusion studies to estimate fractional syn thetic rates of individual hepatic export proteins. However, hippurate tends to overestimate precursor enrichment. Since glycine is rapidly converted to serine by liver cells. we compared tracer enrichment in h ippurate and serine with that of glycine incorporated into apolipoprot ein (apo) B-100. Ten healthy control subjects were studied in the post absorptive state during an 8-hour primed-constant infusion of [N-15]gl ycine (10 mu mol . kg(-1) . h(-1)). Apo B of very-low-density lipoprot ein (VLDL) was isolated by standard ultracentrifugation and isopropano l precipitation. Glycine and serine were isolated from plasma and hydr olyzed apo B, hippurate was isolated from plasma, and [N-15]enrichment was determined by gas chromatography-mass spectrometry. Enrichment in serine and glycine isolated from apo B was identical at all time poin ts, and their enrichment in apo B increased asymptotically, approachin g an apparent plateau (mean +/- SD: 91% +/- 10% of calculated plateau at 8 hours) that was taken to represent hepatic protein precursor enri chment. Enrichment in both plasma serine and hippurate followed a biph asic pattern and continued to increase until the end of the study, rai sing the possibility that precursor enrichment had not reached a stead y state during the study. The apo B plateau was lower (factor 0.76 +/- 0.27) than the final enrichment in hippurate and higher (factor 1.38 +/- 0.36) than that in plasma serine; however, predictions of protein precursor enrichment based on either metabolite were flawed by a large coefficient of variation (35% v 26%). We conclude that glycine enrich ment in the hepatic protein precursor pool may not be constant during an 8-hour infusion study, and that only a rough approximation of this level may be obtained using either enrichment in plasma hippurate or p lasma serine. Copyright (C) 1995 by W.B. Saunders Company