Table 1.
Intestinal and hepatic UGT protein abundance and mRNA expression 1.
Small Intestine (pmol/mg prot) | Liver (pmol/mg prot) | Small Intestine/Liver Ratio 2 | Small Intestine (pmol/mg prot) | Liver (pmol/mg prot) | Small Intestine/Liver Ratio | Small Intestine/Liver Ratio | Small Intestine (pmol/mg prot) | Liver (pmol/mg prot) | Small Intestine/Liver Ratio | Small Intestine (Copy Number Normalized to GAPDH) | Liver (Copy Number Normalized to GAPDH) | Small Intestine/Liver Ratio | Small Intestine/Liver Ratio Assumed in ACAT Model Built in GP 9.8 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
UGT1A1 | 7.2 | 18.3 | 0.0157 | 39.6 | 124 | 0.0128 | 0.0280 | 0.33 | 0.87 | 0.0152 | 582 | 1430 | 0.0326 | 0.0196 |
UGT1A3 | <0.5 | 9.9 | 1.93 | 20.6 | 0.0037 | 0.00284 | 0.04 | 0.3 | 0.0053 | 24 | 131 | 0.0149 | NA | |
UGT1A4 | 5.3 | 4.6 | 0.0461 | 1.6 | 84 | 0.0008 | <0.99 | 3.95 | BLQ | 618 | 0.0462 | |||
UGT1A5 | 72 | 9 | 0.667 | 0.401 | ||||||||||
UGT1A6 | 2.3 | 5.2 | 0.0177 | <2 | 22.6 | <0.22 | 1.02 | 95 | 468 | 0.0162 | 0.0188 | |||
UGT1A7 3 | 8.4 | BLQ | <2 | <1 | 26 | 5 | 0.4150 | 4.52 3 | ||||||
UGT1A8 3 | 6.1 | BLQ | <2 | <1 | 70 | BLQ | NA 3 | |||||||
UGT1A9 | 6.6 | 26.7 | 0.0099 | <2 | 61.2 | <0.03 | 1.43 | 38 | 1210 | 0.0025 | 0.0156 | |||
UGT1A10 3 | 4.7 | BLQ | 17.9 | <1 | 4.35 | <1.91 | 968 | BLQ | NA 3 | |||||
UGT2B7 | 15.7 | 200 | 0.0031 | 0.00589 | 0.77 | 6.01 | 0.0051 | 1930 | 4220 | 0.0366 | 0.0268 | |||
UGT2B15 | <2 | 99.7 | <0.72 | 3.76 | 738 | 18,500 | 0.00319 | 0.00496 | ||||||
UGT2B17 | 112 | 54.3 | 0.0825 | 1.91 | 0.21 | 0.364 | 2680 | 197 | 1.09 | 0.655 | ||||
Source | Harbourt et al. [9] 4 | Sato et al. [11] 4 | Drozdzik et al. [34] 5 | Basit et al. [8] 6 | Ohno and Shizuo [10] 4 | |||||||||
Sample type | Microsome fraction | Microsome fraction | Tissue homogenate | S9 fraction | Total RNA |
1 Results below the limit of quantification or limit of detection = BLQ. Uridine 5′-diphospho-glucuronosyltransferase = UGT. Empty cells indicate no data. 2 The small intestine-to-liver ratio is the ratio of the estimated total small intestine abundance to the total hepatic abundance using the data from the same study for both tissues. These are calculated assuming total microsomal (or S9) protein abundance in the small intestine is 4% of total microsomal (or S9) protein abundance in the liver. Total RNA samples are assumed to represent the UGT levels in intestinal mucosa; intestine to liver ratio is calculated assuming intestinal mucosa mass is 8% of liver mass. 3 UGT1A7, UGT1A8, and UGT1A10 are considered to be extrahepatic enzymes [29]. However, low hepatic UGT1A7 expression has been reported [10] and has been used for parameterizing the current GastroPlus physiology model. Otherwise, the intestinal abundance of extrahepatic enzymes is represented relative to the whole small intestine instead of relative to liver in the ACAT model. 4 Harbourt et al. [9], Sato et al. [11] and Ohno and Shizuo [10] report UGT levels in the human small intestine without specifying the part of small intestine used for sample preparation. 5 Drozdzik et al. [34] report UGT abundance in several segments of intestine and include estimates of total small intestine and liver UGT protein abundance. 6 Basit et al. [8] report UGT abundance in samples prepared from the first half of the small intestine.