Tissue distribution of human enzymes involved in prodrug activation
| Liver | Kidney | Intestine | Brain | Lung | Adrenal | Testis | Skin | Spleen | Heart | Serum | Stomach | Lymph node | Muscle | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aldehyde oxidasea | ++ | +/++ | + | ND | ++ | ++ | ++ | ND | − | ND | − | ± | − | ND |
| Amino acid oxidaseb | ||||||||||||||
| l-AAO | 0.33 | 0.35 | − | ND | ND | − | − | − | ND | ND | ND | − | − | − |
| d-AAO | 4.51 | 5.94 | − | 0.48 | ND | − | − | − | ND | ND | ND | − | − | − |
| Cytochrome P450c | 0.26−1.02 | 0.03 | − | − | − | 0.23−0.54 | 0.005 | − | − | − | − | − | − | − |
| DT-diaphorased | 17 | 117 | 17 | − | 10 | − | − | − | − | − | − | 387 | − | − |
| Thymidine phosphorylasee | 1.37 | 0.22 | 0.42 | − | 1.44 | − | − | − | 1.12 | 0.35 | − | 0.23 | 1.51 | ND |
| Glutathione S-transferasef | ||||||||||||||
| Cytosolic | 1.80 | 1.41 | 0.66 | − | 0.61 | − | − | − | − | − | − | − | − | − |
| Microsomal | 100 | 34 | 23 | 24 | 15 | − | − | 1 | 14 | − | − | − | 3 | |
| Deoxycytidine kinaseg | − | − | 37 | 14 | − | − | − | − | − | 36 | − | − | − | 11 |
| Cysteine conjugate β-lyaseh | 0.43 | 0.13 | − | − | − | − | − | − | − | − | − | − | − | − |
ND, no detectable enzyme activity or no staining observed; −, no data available.
↵ a Based on immunohistochemical staining. ±, equivocal staining; +, low staining; ++, moderate staining (Moriwaki et al., 2001).
↵ b Expressed as μmol/min/mg for four individuals with d-alanine as a substrate (Holme and Goldberg, 1982).
↵ c Expressed as nmol/mg of microsomal protein (Vainio, 1980).
↵ d Expressed as nmol/min/mg of protein with dichloroindophenol as a substrate (Schlager and Powis, 1990). A similar tissue distribution was observed with menadione as a substrate.
↵ e Expressed as nmol/h/mg of protein with thymidine as a substrate; intestine activity represents the sum of colon and small intestine (Yoshimura et al., 1990).
↵ f Cytosolic GST expressed as nmol/min/mg of protein with benzo[a]pyrene-4,5-oxide as a substrate (Pacifici et al, 1988). Microsomal GST expressed as percentage of liver mRNA expression that is known to closely correlate with GST protein and enzyme activity (Buetler et al., 1995; Estonius et al., 1999).
↵ g Expressed as pmol/min/mg of protein with deoxycytidine as a substrate (Arner et al., 1992, #559). Intestine value represents colon, and heart value represents ventricle.
↵ h Expressed as nmol/min/mg of protein with S-(2-chloro-1,1,2-trifluoroethyl)-l-cysteine as a substrate (Rooseboom et al., 2000, 2002). Similar tissue distribution was observed with various SeCys conjugates (Rooseboom et al., 2002).