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Literature summary for 2.4.1.17 extracted from

  • Blevins-Primeau, A.S.; Sun, D.; Chen, G.; Sharma, A.K.; Gallagher, C.J.; Amin, S.; Lazarus, P.
    Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites (2009), Cancer Res., 69, 1892-1900.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.4.1.17

Application

Application Comment Organism
pharmacology isoform UGT1A8173Ala/277Tyr variant exhibits no detectable glucuronidation activity against the trans isomers of either 4-hydroxytamoxifen or endoxifen. Little or no difference in tamoxifen glucuronidating activity is observed for the UGT1A8173Gly/277Cys or UGT1A10139Lys variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7268Tyr variant exhibits significant 2- and 5fold decreases in activity against the trans isomers of 4-hydroxytamoxifen and endoxifen, respectively, compared with wild-type UGT2B7268His. Functional polymorphisms in tamoxifen-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in tamoxifen metabolism and response to tamoxifen therapy Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information isoform UGT1A8173Ala/277Tyr variant exhibits no detectable glucuronidation activity against the trans isomers of either 4-hydroxytamoxifen or endoxifen. Little or no difference in tamoxifen glucuronidating activity is observed for the UGT1A8173Gly/277Cys or UGT1A10139Lys variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7268Tyr variant exhibits significant 2- and 5fold decreases in activity against the trans isomers of 4-hydroxytamoxifen and endoxifen, respectively, compared with wild-type UGT2B7268His Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0037
-
 trans-4-hydroxytamoxifen isoform UGT2B7, variant 268His, pH 7.4, 37°C Homo sapiens
0.0087
-
 trans-4-hydroxytamoxifen isoform UGT2B7, variant 268Tyr, pH 7.4, 37°C Homo sapiens
0.013
-
 trans-endoxifen isoform UGTA10, variant 139Lys, pH 7.4, 37°C Homo sapiens
0.023
-
 trans-4-hydroxytamoxifen isoform UGT1A8, variant 173Ala/277Cys, pH 7.4, 37°C Homo sapiens
0.04
-
 trans-endoxifen isoform UGTA10, variant 139Glu, pH 7.4, 37°C Homo sapiens
0.043
-
 trans-4-hydroxytamoxifen isoform UGT1A8, variant 173Gly/277Cys, pH 7.4, 37°C Homo sapiens
0.052
-
 trans-4-hydroxytamoxifen isoform UGTA10, variant 139Lys, pH 7.4, 37°C Homo sapiens
0.096
-
 trans-4-hydroxytamoxifen isoform UGTA10, variant 139Glu, pH 7.4, 37°C Homo sapiens
0.098
-
 trans-endoxifen isoform UGT1A8, variant 173Ala/277Cys, pH 7.4, 37°C Homo sapiens
0.101
-
 trans-endoxifen isoform UGT2B7, variant 268His, pH 7.4, 37°C Homo sapiens
0.101
-
 trans-endoxifen isoform UGT2B7, variant 268Tyr, pH 7.4, 37°C Homo sapiens
0.135
-
 trans-endoxifen isoform UGT1A8, variant 173Gly/277Cys, pH 7.4, 37°C Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
tamoxifen + UDP-glucuronate
-
 Homo sapiens UDP + ?
-
 ?
trans-4-hydroxytamoxifen + UDP-glucuronate
-
 Homo sapiens UDP + ?
-
 ?
trans-endoxifen + UDP-glucuronate
-
 Homo sapiens UDP + ?
-
 ?