A comparative review of the structure and biosynthesis of thyroglobulin

Thyroglobulin, the major iodoglycoprotein of the thyroid (M-r 669 kDa) has a sedimentation coefficient of 19 S and an isoelectric point (pI) of 4.4-4. 7. The protein has been isolated and purified from saline extracts of the g land of several animal species, by methods such as ammonium sulfate fractio nation, DEAE-cellulose chromatography and Sepharose 4B/6B gel-filtration. D EAE-cellulose chromatography of thyroglobulin from many species, by linear gradient, yielded a complex elution pattern, while camel thyroglobulin show ed only a major and minor peak. As an iodoprotein, the protein has 0.1-2.0% iodine. The amino acid and iodoamino acid composition of thyroglobulins, i n general, is similar. However, a high thyroxine content (15 mol/mol protei n) has been noted for buffalo species. Asparagine or aspartic acid has been reported as the major N-terminal amino acid for thyroglobulins of several animal species whereas glutamic acid is the sole N-terminal amino acid for buffalo thyroglobulin. As a glycoprotein, thyroglobulin contains 8-10% tota l carbohydrate with galactose, mannose, fucose, N-acetyl glucosamine and si alic acid residues. The carbohydrate in the protein is distributed as two d istinct units, A and B. In addition, human thyroglobulin has carbohydrate u nit C. The occurrence of sulfate and phosphate as Gal-3-SO4 and Man-6-PO4, respectively, has been reported in few species. The quaternary structure of native thyroglobulin is comprised of two equal sized subunits of 330 kDa. However, the protein appears to contain 4-8 non-identical units in few spec ies. The synthesis of thyroid hormones occurs in the matrix of the protein and is regulated by pituitary thyrotropin. The role of tyrosine residues 5 and 130 in thyroxine synthesis has been well documented. (C) 1999 Elsevier Science Inc. All rights reserved.