Orosomucoid Explained

orosomucoid 1
Hgncid:8498
Symbol:ORM1
Entrezgene:5004
Omim:138600
Refseq:NM_000607
Uniprot:P02763
Chromosome:9
Arm:q
Band:31
Locussupplementarydata:-qter
orosomucoid 2
Hgncid:8499
Symbol:ORM2
Entrezgene:5005
Omim:138610
Refseq:NM_000608
Uniprot:P19652
Chromosome:9
Arm:q
Band:31
Locussupplementarydata:-qter

Orosomucoid (ORM) or alpha-1-acid glycoprotein (α1AGp, AGP or AAG) is an acute phase protein found in plasma. It is an 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).[1] Plasma levels are affected by pregnancy, burns, certain drugs, and certain diseases, particularly HIV.[1]

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 (negatively charged) drugs (whereas albumin carries acidic (positively charged) and neutral drugs), steroids, and protease inhibitors.[1] [2] 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.[3] AGP shows a complex interaction with thyroid homeostasis: AGP in low concentrations was observed to stimulate the thyrotropin (TSH) receptor and intracellular accumulation of cyclic AMP. High AGP concentrations, however, inhibited TSH signalling.[4] [5]

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).[6]

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

See also

Notes and References

  1. Colombo S, Buclin T, Décosterd LA, Telenti A, Furrer H, Lee BL, Biollaz J, Eap CB . 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 . October 2006 . 17015049 . 10.1016/j.clpt.2006.06.006 . 684478 .
  2. Urien S, Brée F, Testa B, Tillement JP . pH-dependency of basic ligand binding to alpha 1-acid glycoprotein (orosomucoid) . The Biochemical Journal . 280 (Pt 1) . 1 . 277–80 . November 1991 . 1741754 . 1130632 . 10.1042/bj2800277.
  3. Book: Rooke GA . Anesthesia for the Older Patient . Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC . Clinical Anesthesia . Lippincott Williams & Wilkins . 2009 . 978-0-7817-8763-5 . 879 .
  4. Zimmermann-Belsing T, Rasmussen AK, Feldt-Rasmussen U, Bøg-Hansen TC . 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 . February 2002 . 11911961 . 10.1016/s0303-7207(01)00650-5 . 22815279 .
  5. Dietrich JW, Landgrafe G, Fotiadou EH . TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis . Journal of Thyroid Research . 2012 . 351864 . 2012 . 23365787 . 3544290 . 10.1155/2012/351864 . free .
  6. 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 . 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 . February 2014 . 24586121 . 3934819 . 10.1371/journal.pmed.1001606 . free .