Sodium/bile acid cotransporter also known as the Na⁺- taurocholate

cotransport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

ing

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

(NTCP) or

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...

transporter (LBAT) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''SLC10A1'' (solute carrier family 10 member 1)

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Structure

Sodium/bile acid

cotransporter Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They e ...

s are integral membrane glycoproteins. Human NTCP contains 349 amino acids and has a mass of 56 kDa.

Function

Bile acid:sodium symporters participate in the

enterohepatic circulation Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Ent ...

s. Two homologous transporters are involved in the reabsorption of bile acids. One of these absorbs bile acids from the intestinal lumen, the bile duct, and the kidney with an apical localization ( ileal sodium/bile acid cotransporter). The other is this protein and is expressed in the

basolateral membrane Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via the ...

s of hepatocytes (NTCP). As a cotransporter, NTCP binds two sodium ions and one (conjugated)

bile salt Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Prima ...

molecule, thereby providing a

hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

influx of bile salts. Other transported molecules include

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Wi ...

thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

s and various

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

Hepatitis virus entry

NTCP is a cell surface receptor necessary for the entry of

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

and

hepatitis D virus Hepatitis D is a type of viral hepatitis caused by the hepatitis delta virus (HDV). HDV is one of five known hepatitis viruses: hepatitis A, A, hepatitis B, B, hepatitis C, C, D, and hepatitis E, E. HDV is considered to be a Satellite (biology), s ...

. This entry mechanism is inhibited by

myrcludex B Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication for the treatment of chronic hepatitis D (in the presence of hepatitis B). The most common side effects include raised levels of bile salts in the blood and reactions ...

cyclosporin A Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, ...

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

propranolol Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anx ...

bosentan Bosentan, sold under the brand name Tracleer and Safebo among others, is a dual endothelin receptor antagonist medication used in the treatment of pulmonary artery hypertension (PAH). Bosentan is available as film-coated tablets (62.5 mg o ...

ezetimibe Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also ...

bexarotene Bexarotene, sold under the brand Targretin, is an antineoplastic (anti-cancer) agent used for the treatment of cutaneous T cell lymphoma (CTCL). It is a third-generation retinoid. It was approved by the U.S. Food and Drug Administration (FDA) ...

as well as NTCP substrates like taurocholate, tauroursodeoxycholate and bromosulfophthalein.

SLC10A1-deficiency

Individuals that lack functional NTCP have been identified. These individuals display highly elevated bile salt levels in plasma, but without a clear phenotype. In areas of the world with a high prevalence of HBV, there are multiple individuals who carry the NTCP p.S267F polymorphism on both alleles; this makes NTCP inactive as a bile acid transporter, but provides protection against HBV infection. NTCP-deficient mice have also been created. These mice have reduced hepatic bile salt uptake but plasma bile salt levels are less clearly elevated, as the rodent-specific OATP1a/1b transporters provide can partially replace the function of NTCP. Nevertheless, this NTCP-knockout animal model pointed to possible additional (non-HBV) aspects of NTCP-deficiency. NTCP-deficient mice are partially protected against the problems associated with a high-calorie diet, including excessive weight gain and to liver damage in cholestasis. These effects of NTCP deficiency have not yet been replicated in humans.

Structure

Function

Hepatitis virus entry

SLC10A1-deficiency

See also

References

Further reading