Comparative Biochemistry and Physiology Part B 134 (2003) 189–197 1096-4959/03/$ - see front matter  2002 Elsevier Science Inc. All rights reserved. PII: S1096-4959 Ž 02 . 00250-6 Turkey intestine as a commercial source of heparin? Comparative structural studies of intestinal avian and mammalian glycosaminoglycans Mohamad Warda , Wenjun Mao , Toshihiko Toida , Robert J. Linhardt * a b c b, Department of Biochemistry Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt a Department of Chemistry, Department of Chemical and Biochemical Engineering, b Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan c Received 26 October 2002; received in revised form 30 October 2002; accepted 1 November 2002 Abstract Heparin is a glycosaminoglycan (GAG) that is extracted primarily from porcine intestinal tissues and is widely used as a clinical anticoagulant. It is biosynthesized as a proteoglycan and stored exclusively in mast cells and is partially degraded to peptidoglycan and GAG on immunologically activated mast cell degranulation. In contrast, the structurally related heparan sulfate, is the polysaccharide portion of a ubiquitous proteoglycan, localized on cell surface and in the extracellular matrix of all animal tissues. Heparin and heparan sulfate are made in the Golgi through a similar biosynthetic pathway. The current study was undertaken in a search for alternative, non-mammalian, sources of anticoagulant heparin. The heparinyheparan sulfate family of GAGs, prepared and purified from turkey intestine, were assayed for anticoagulant activity and structurally characterized. The resulting GAGs displayed a very low anticoagulant activity when compared to those obtained from porcine intestine using an identical procedure. Structural characterization studies clearly demonstrate that heparan sulfate is the major GAG in the turkey intestine. This observation is rationalized based on differences in the mammalian and avian coagulation and immune systems.  2002 Elsevier Science Inc. All rights reserved. Keywords: Heparin; Heparin sulfate; Avian; Mammalian; Intestine 1. Introduction Commercial manufacture of heparin relies on either porcine intestinal or bovine lung tissue as the raw material. These tissues are rich in mast cells, presumably resulting from the high foreign parasite burden in these tissues, e.g. bacteria and viruses (Vaheri, 1964; Regelson, 1968; Weiss, 1977). The appearance of bovine spongiform *Corresponding author. Tel.: q1-319-335-8834; fax: q1- 319-335-6634. E-mail address: Robert-linhardt@uiowa.edu (R.J. Linhardt). encephalopathy, ‘mad cow disease’, and its appar- ent link to the similar prion-based Creutzfeldt- Jakob disease in humans (Schonberger, 1998), has limited the use of bovine heparin. Moreover, it is not easy to distinguish bovine and porcine hepa- rins, making it difficult to ensure the species source of heparin (Linhardt and Gunay, 1999). Heparin exhibits anticoagulant activity primarily from its binding to the serine protease inhibitor (SERPIN) antithrombin III, which undergoes a conformation- al change, becoming a potent inhibitor of thrombin (factor IIa) and factor Xa, serine proteases of the coagulation cascade (Jordan et al., 1980a,b, 1982).