Orosomucoid

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orosomucoid 1
Identifiers
SymbolORM1
Entrez5004
HUGO8498
OMIM138600
RefSeqNM_000607
UniProtP02763
Other data
LocusChr. 9 q31-qter
orosomucoid 2
Identifiers
SymbolORM2
Entrez5005
HUGO8499
OMIM138610
RefSeqNM_000608
UniProtP19652
Other data
LocusChr. 9 q31-qter

Orosomucoid (ORM) or alpha-1-acid glycoprotein (α1AGp,[1] AGP or AAG) is an acute phase (acute phase protein) plasma alpha-globulin glycoprotein and is modulated by two polymorphic genes. It is synthesized primarily in hepatocytes and has a normal plasma concentration between 0.6-1.2 mg/mL (1-3% plasma protein).[2] Plasma levels are affected by pregnancy, burns, certain drugs, and certain diseases, particularly HIV.[2]

The only established function of ORM is to act as a carrier of basic and neutrally charged lipophilic compounds. In medicine, it is known as the primary carrier of basic (positively charged) drugs (whereas albumin carries acidic (negatively charged) and neutral drugs), steroids, and protease inhibitors.[2][3] Aging causes a small decrease in plasma albumin levels; if anything, there is a small increase in alpha-1-acid glycoprotein. The effect of these changes on drug protein binding and drug delivery, however, appear to be minimal.[4] AGP shows a complex interaction with thyroid homeostasis: ORM in low concentrations was observed to stimulate the thyrotropin (TSH) receptor and intracellular accumulation of cyclic AMP. High AGP concentrations, however, inhibited TSH signalling.[5][6]

Alpha-1-acid glycoprotein has been identified as one of four potentially useful circulating biomarkers for estimating the five-year risk of all-cause mortality (the other three are albumin, very low-density lipoprotein particle size, and citrate).[7]

Orosomucoid increases in amount in obstructive jaundices while diminishes in hepatocellular jaundice and in intestinal infections.

References

  1. Logan, Carolynn M.; Rice, M. Katherine (1987). Logan's Medical and Scientific Abbreviations. Philadelphia: J. B. Lippincott Company. p. 3. ISBN 0-397-54589-4.
  2. 2.0 2.1 2.2 Colombo S, Buclin T, Décosterd LA, Telenti A, Furrer H, Lee BL, Biollaz J, Eap CB (October 2006). "Orosomucoid (alpha1-acid glycoprotein) plasma concentration and genetic variants: effects on human immunodeficiency virus protease inhibitor clearance and cellular accumulation". Clinical Pharmacology and Therapeutics. 80 (4): 307–18. doi:10.1016/j.clpt.2006.06.006. PMID 17015049.
  3. Urien S, Brée F, Testa B, Tillement JP (November 1991). "pH-dependency of basic ligand binding to alpha 1-acid glycoprotein (orosomucoid)". The Biochemical Journal. 280 ( Pt 1) (1): 277–80. PMC 1130632. PMID 1741754.
  4. Rooke GA (2009). "Anesthesia for the Older Patient". In Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Clinical Anesthesia. Lippincott Williams & Wilkins. p. 879. ISBN 978-0-7817-8763-5.
  5. Zimmermann-Belsing T, Rasmussen AK, Feldt-Rasmussen U, Bøg-Hansen TC (February 2002). "The influence of alpha1-acid glycoprotein (orosomucoid) and its glycoforms on the function of human thyrocytes and CHO cells transfected with the human TSH receptor". Molecular and Cellular Endocrinology. 188 (1–2): 241–51. doi:10.1016/s0303-7207(01)00650-5. PMID 11911961.
  6. Dietrich JW, Landgrafe G, Fotiadou EH (2012). "TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis". Journal of Thyroid Research. 2012: 351864. doi:10.1155/2012/351864. PMC 3544290. PMID 23365787.
  7. Fischer K, Kettunen J, Würtz P, Haller T, Havulinna AS, Kangas AJ, Soininen P, Esko T, Tammesoo ML, Mägi R, Smit S, Palotie A, Ripatti S, Salomaa V, Ala-Korpela M, Perola M, Metspalu A (February 2014). "Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons". PLoS Medicine. 11 (2): e1001606. doi:10.1371/journal.pmed.1001606. PMC 3934819. PMID 24586121.

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