Variation in retinol utilization rate with vitamin A status in the rat

The relationship of vitamin A status to retinol (ROH) utilization rate (disposal rate, DR) and other kinetic parameters was studied in rats with low (LO), marginal (MAR) or high (HI) mean liver vitamin A levels (2.2, 43 and 985 micrograms, respectively) and low or normal plasma ROH concentrations (6.8, 46 and 42 micrograms/dL). Kinetic parameters were calculated by input-output analysis of plasma [3H]ROH turnover monitored for 35 (LO and MAR) or 115 d (HI) after injection of [3H]ROH in its plasma transport complex. There was a highly significant negative correlation between fraction of dose in plasma 5 d after injection of [3H]ROH and the natural log of liver total vitamin A. The total time an average ROH molecule spent in plasma (residence time), as well as the time spent during each pass (transit time), was significantly lower in HI (0.77 d and 1.9 h) than in LO (0.98 d and 2.7 h) and MAR (0.92 d and 2.8 h) rats; however, the total time in the system (mean sojourn time) increased markedly with vitamin A status (5, 18 and 77 d). The number of times an average ROH molecule recycled through plasma before irreversible loss (7-9 times) was similar in all groups. Most of the ROH molecules (approximately 90%) that left the plasma were recycled, not irreversibly metabolized, in all groups. Among groups, ROH DR increased significantly from 1.2 (LO) to 8.0 (MAR) to 11.8 micrograms/d (HI). For LO versus MAR and LO versus HI, differences in DR were positively related to differences in the plasma ROH pool size. These results suggest that low plasma ROH concentrations are associated not only with low liver vitamin A levels, but also with a decreased ROH DR. This decreased DR may or may not reflect a compromised functioning of ROH-dependent systems.