Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large family (14 children) with congenital goiter whose parents are first cousins was studied. Thyroid tissue was obtained, after 125I in vivo labeling, from one of the siblings (JBM). Gel filtration of thyroid proteins indicated that thyroglobulin (Tg) eluted as a single symmetrical peak in the same position as authentic 19S Tg. Gel electrophoresis in a 7.5% sodium dodecyl sulfate-polyacrylamide gel revealed a major band with the same mobility and immunoreactivity as normal 19S Tg. Hydrolysis of the patient's Tg indicated that most of the radioactivity was mono- and diiodotyrosines. The yield of T4 from JBM Tg (26 pmol/mg protein) was 5-fold less than normal thyroid tissue (140 pmol/mg protein) and approximately half of that in thyroid tissue from endemic goiter (51 pmol/mg). Total T3 released from JBM Tg was similar to the other two tissues. When the carbohydrate content of normal and patient Tg was analyzed, there was no differences in glucosamine, galactose or mannose content. However, unlike normal and endemic-goiter Tg, that had a mean sialic acid content of 7.3 and 5.6 micrograms/mg protein, respectively, the sialic acid concentration of the patients Tg was only 0.3 microgram/mg. Sialyltransferase activity was readily demonstrated in homogenate from normal thyroid or endemic goiter, but no sialyltransferase activity was detectable in a homogenate of JBM-thyroid tissue. We conclude that the finding of severely hyposialylated Tg is linked to a defect in iodotyrosine coupling seen in this patient with a possibly abnormal migration of Tg into the follicular lumen.
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PMID:Hyposialylated thyroglobulin in a patient with congenital goiter and hypothyroidism. 172 28

The integrity of the Tg structure as a protein is essential for adequate synthesis of thyroid hormone. Also a large supply of iodine and of thyroid hormone is stored into the Tg molecule and available for secretion on demand. Mutations in Tg gene or hyposialylated Tg due to a defective sialyltransferase activity would cause a structurally defective protein and severely impair the functional ability of Tg. In this review we attempt to cover the abnormalities in the synthesis of Tg described in both animals and man. Hereditary congenital goiter with or without hypothyroidism is the phenotypic major clinical finding in these species. Affected animals include sheep, bovine cattle, bongo antelope, goats, and mice. As in man the inheritance mode is autosomal recessive. In most animal studies structurally abnormal Tg is present. The molecular basis for the defective Tg synthesis was attributable to nonsense mutation in exon 9 (Afrikander cattle) and in exon 8 (Dutch goats). In man the Tg defective synthesis has been reported in 89 subjects and frequently more than one sibling is affected in a given generation. Characteristically these patients exhibit hereditary congenital goiter with relatively low Tg levels that do not increase after stimulation with bovine TSH. High PBI concentrations with low serum T4 values indicate the serum presence of iodinated proteins (mainly iodoalbumin). Also iodinated peptides are frequently excreted into the urine. Tissue studies confirm that there is an absent Tg peak at gel filtration, and virtually no immunoassayable Tg is present in the tissue extracts. The molecular basis of these defects have been recently reported in a patient and includes low tissue Tg mRNA probably due to premature degradation of a defective Tg mRNA. The responsible mutation is a cytosine to thymine transition creating a stop codon at position 1510. The point mutation is removed by the preferential accumulation of a 171 nt deleted Tg mRNA. In another subject molecular studies revealed that exon 4 was missing from the major Tg transcript due to a cytosine to guanine transversion at position minus 3 in the acceptor splice site of intron 3. It is anticipated that other mutations responsible for these defects will be identifiable in the near future.
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PMID:Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism. 832 50

Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor.
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PMID:Thyroid sialyltransferase mRNA level and activity are increased in Graves' disease. 1605 79