Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase isoform 8: Cloning, tissue distribution, gene structure, and enzymatic activity

2006 ◽  
Vol 449 (1-2) ◽  
pp. 64-76 ◽  
Author(s):  
Anil K. Agarwal ◽  
Robert I. Barnes ◽  
Abhimanyu Garg
Keyword(s):  
Enzymatic Activity ◽  
Tissue Distribution ◽  
Gene Structure ◽  
Functional Characterization

The Tissue Distribution and Functional Characterization of Human VR1

2001 ◽  
Vol 281 (5) ◽  
pp. 1183-1189 ◽  
Author(s):  
Daniel N. Cortright ◽  
Marci Crandall ◽  
Jennifer F. Sanchez ◽  
Tong Zou ◽  
James E. Krause ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Functional Characterization

scholarly journals Functional Characterization of 21 Rare Allelic CYP1A2 Variants Identified in a Population of 4773 Japanese Individuals by Assessing Phenacetin O-Deethylation

2021 ◽  
Vol 11 (8) ◽  
pp. 690
Author(s):  
Masaki Kumondai ◽  
Evelyn Marie Gutiérrez Rico ◽  
Eiji Hishinuma ◽  
Yuya Nakanishi ◽  
Shuki Yamazaki ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Protein Function ◽  
Rare Variants ◽  
Functional Characterization ◽  
Three Dimensional ◽  
Additional Information ◽  
Metabolic Reactions ◽  
Underlying Mechanisms ◽  
Cytochrome Content

Cytochrome P450 1A2 (CYP1A2), which accounts for approximately 13% of the total hepatic cytochrome content, catalyzes the metabolic reactions of approximately 9% of frequently used drugs, including theophylline and olanzapine. Substantial inter-individual differences in enzymatic activity have been observed among patients, which could be caused by genetic polymorphisms. Therefore, we functionally characterized 21 novel CYP1A2 variants identified in 4773 Japanese individuals by determining the kinetic parameters of phenacetin O-deethylation. Our results showed that most of the evaluated variants exhibited decreased or no enzymatic activity, which may be attributed to potential structural alterations. Notably, the Leu98Gln, Gly233Arg, Ser380del Gly454Asp, and Arg457Trp variants did not exhibit quantifiable enzymatic activity. Additionally, three-dimensional (3D) docking analyses were performed to further understand the underlying mechanisms behind variant pharmacokinetics. Our data further suggest that despite mutations occurring on the protein surface, accumulating interactions could result in the impairment of protein function through the destabilization of binding regions and changes in protein folding. Therefore, our findings provide additional information regarding rare CYP1A2 genetic variants and how their underlying effects could clarify discrepancies noted in previous phenotypical studies. This would allow the improvement of personalized therapeutics and highlight the importance of identifying and characterizing rare variants.

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