Sodium taurocholate transporting polypeptide

Since their discovery as heme thiolate proteins in the late-1950s, the cytochrome P450s have been recognized as the largest family of enzymes 

Unfavorable DDIs are clearly important and clinically relevant. Even though in some populations the number of DDIs may seem small, they are an important factor in determining whether or not a new chemical entity will successfully make it beyond a drug discovery program to development. In addition, the late discovery of a clinically significant DDI could be costly in terms of the financial investment of a particular project. Therefore it is important to screen for potential interactions early on, to aid in the selection of the most appropriate in vivo studies. In this regard, drug interactions with cyto- 

The CYPs may be involved in many DDIs because of their affinity for hydrophobic molecules of varying sizes. It is widely believed that an understanding of DDIs at the molecular level may lead to the development of more effective and safer therapeutics. In the absence of a freely available crystal structure for any of the human CYPs, there is an obvious need to build computational models in an attempt to predict drug metabolism and 

Members of the CYP3A family of enzymes are the most important in terms of human drug metabolism,because they have wide substrate 

---

Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR (1999) Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther 291, 1204-1209. 

Fig. 5. Transport of bile acids in the enterohepatic circulation. The left and right sides of the figure depict a liver and intestinal cell, respectively. Bile acids (BA) are made from unesterified cholesterol (UC) in the liver. The movement of bile acids in the enterohepatic circulation is vectorial. The major transporters thought to be responsible for the entry and exit of bile acids in liver and intestinal cells are sodium/taurocholate cotransporting polypeptide (ntcp SLClOAl), bile salt export pump (bsep ABCBll), apical/sodium bile acid cotransporter (asbt SLC10A2), and organic solute transporters a/p, (Osta/P).

ABC, ATP-binding cassette transporter superfamily ASBT, apical sodium-dependent bile salt transporter BCRP, breast cancer resistance protein BSEP, bile salt export pump MDRl, multidrug resistance MRR multidrug resistance-related protein NTCP, sodium taurocholate cotransporting polypeptide OAT, organic anion transporter OCT, organic cation transporter SLC, solute-linked carrier transporter family SLCO, solute-linked carrier organic anion transporter family. 

Wilkinson,. Pharmacol. Exp. Ther., 291, 1204 (1999). Modulation by Drugs of Human Hepatic Sodium-Dependent Bile Acid Transporter (Sodium Taurocholate Cotransporting Polypeptide) Activity. 

Figure 2.1 Hepatocyte basolateral bile acid transporters. Protein-bound bile acids returning in portal blood are taken up by the hepatocyte via the sodium taurocholate co-transporting polypeptide (NTCP) and organic-anion-transporting polypeptide (OATP). In cholestasis bile acids may be returned to blood by the multi-drug-resistance-associated protein 3 (MRP3).

Kouzuki, H., Suzuki, H., Ito, K., Ohashi, R. and Sugiyama, Y. (1998) Contribution of sodium taurocholate co-transporting polypeptide to the uptake of its possible substrates into rat hepatocytes. The Journal of Pharmacology and Experimental Therapeutics, 286, 1043-1050. 

---