5′-Nucleotidase 

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5′-Nucleotidase (5NT) is an intrinsic membrane glycoprotein that is present as an enzyme in a wide variety of mammalian cells. ^[1] It facilitates the hydrolysis of the phosphate group from 5’-nucleotides, resulting in corresponding nucleosides.

The reference range of 5NT is 2-15 U/L. ^[2]

5’-Nucleotidase (5NT) levels are elevated the following:

Obstructive or cholestatic liver disease

Hepatitis

Intrinsic liver damage

Primary liver malignancy and metastasis

Biliary cirrhosis

Use of hepatotoxic drugs

Specimen: Serum separation tube (SST)

Container: Vacutainer, red/black top (SST; see image below)

Collect 1 mL; minimum, 0.4 mL

Method: Routine venipuncture

Special instructions: Allow sample to clot completely at room temperature, then separate immediately

Related tests include serum alkaline phosphatase and gamma-glutamyltransferase (GGT).

5′-Nucleotidase (5NT) is an intrinsic membrane glycoprotein that is present as an enzyme in a wide variety of mammalian cells. ^[1] It facilitates the hydrolysis of the phosphate group from 5’-nucleotides, resulting in corresponding nucleosides.

Despite its widespread distribution in the human body, serum elevations of 5NT are medically useful in identifying hepatobiliary disease.

The test can be used in conjunction with elevated alkaline phosphatase levels or other clinical findings suggestive of liver/gall bladder disease. It is especially useful (in the absence of pregnancy) when the differential diagnoses include hepatobiliary disease processes versus those of an osseous nature because it is not elevated in osteoblastic bone pathologies.

GGT can be used in a similar manner, but, generally, GGT levels are elevated in any hepatocellular injury, while 5NT is more specific to situations resulting in obstructive or cholestatic liver disease. Currently, laboratory testing for GGT is less cumbersome and more available than 5NT. ^{[3, 4, 5, 6, 7]}

The following are pathologic states in which 5NT is elevated:

Obstructive or cholestatic liver disease ^[8]

Hepatitis

Intrinsic liver damage (elevated in acute alcohol use, chronic alcohol use, and cirrhosis)

Malignancy (primary hepatic; metastasis [5NT is especially useful in monitoring/confirming])

Biliary cirrhosis

Nonpathologic conditions in which 5NT levels are elevated include the following:

Pregnancy

Use of hepatotoxic medications (eg, acetaminophen, halothane, isoniazid [INH], methyldopa, nitrofurantoin)

Sunderman FW. The clinical biochemistry of 5′-nucleotidase. Ann Clin Lab Sci. 1990. 20:123-139.

Gomella LG, Haist SA. Laboratory Diagnosis: Chemistry, Immunology, Serology. Gomella LG, Haist SA, eds. Clinician’s Pocket Reference: The Scut Monkey. 11th ed. New York: McGraw-Hill; 2007. Chapter 4.

Burris CA, Ashwood ER, Burns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis: Elsevier Saunders; 2006.

Pagani F, Panteghini M. Biological variation in serum activities of three hepatic enzymes. ClinChem. 2001. 47:355-35.

Zukowska P, Kutryb-Zajac B, Toczek M, Smolenski RT, Slominska EM. The role of ecto-5′-nucleotidase in endothelial dysfunction and vascular pathologies. Pharmacol Rep. 2015 Aug. 67 (4):675-81. [Medline].

Holmes AP, Nunes AR, Cann MJ, Kumar P. Ecto-5′-Nucleotidase, Adenosine and Transmembrane Adenylyl Cyclase Signalling Regulate Basal Carotid Body Chemoafferent Outflow and Establish the Sensitivity to Hypercapnia. Adv Exp Med Biol. 2015. 860:279-89. [Medline].

Wolff G, Truse R, Decking U. Extracellular Adenosine Formation by Ecto-5′-Nucleotidase (CD73) Is No Essential Trigger for Early Phase Ischemic Preconditioning. PLoS One. 2015. 10 (8):e0135086. [Medline].

Snider NT, Altshuler PJ, Wan S, Welling TH, Cavalcoli J, Omary MB. Alternative splicing of human NT5E in cirrhosis and hepatocellular carcinoma produces a negative regulator of ecto-5′-nucleotidase (CD73). Mol Biol Cell. 2014 Dec 15. 25 (25):4024-33. [Medline].

Eshchar J, Rudzki C, Zimmerman HJ. Serum levels of 5′-nucleotidase in disease. Am J ClinPathol. 1967. 47:598-606.

Hill PG, Sammons HG. An Assessment of 5’Nucleotidase as a Liver Function Test. QJM. 1967. 36(4):457-468.

Usman Khalid, MD Resident Physician, Department of Internal Medicine, St Louis University School of Medicine

Usman Khalid, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

Judy Lin, MD

Disclosure: Nothing to disclose.

5′-Nucleotidase 

Research & References of 5′-Nucleotidase |A&C Accounting And Tax Services
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