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Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function
Katsuhisa Inoue1, Lina Zhuang, Vadivel Ganapathy
1Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA.
Biochemical and Biophysical Research Communications
|November 26, 2002
Summary
Researchers cloned and characterized the human sodium-coupled citrate transporter (NaCT), identifying its gene location and expression patterns. This transporter facilitates citrate entry into cells, crucial for metabolic pathways.
Area of Science:
- Molecular Biology
- Biochemistry
- Human Genetics
Background:
- Citrate is a key metabolic intermediate with high blood concentrations.
- Understanding citrate transport is vital for metabolic pathway research.
Purpose of the Study:
- To clone and functionally characterize the human sodium-coupled citrate transporter (NaCT).
- To investigate the transporter's substrate specificity, kinetics, and physiological relevance.
Main Methods:
- Gene cloning and expression in mammalian cells.
- Functional assays measuring citrate uptake.
- Analysis of substrate specificity and transport kinetics.
Main Results:
- Human NaCT (77% identity to rat NaCT) cloned; gene located on chromosome 17p12-13.
- NaCT mRNA predominantly expressed in liver, with moderate levels in brain and testis.
- NaCT mediates Na(+)-coupled, electrogenic citrate transport with high specificity.
- Michaelis-Menten constant for citrate is ~650 µM; transport activation by Na(+) is sigmoidal.
Conclusions:
- Human NaCT is the first identified plasma membrane transporter for preferential cellular citrate uptake.
- NaCT's liver expression and citrate selectivity suggest a role in utilizing circulating citrate for energy, fatty acid, and cholesterol synthesis.