lecture 21: iodine Flashcards
function of iodine
synthesis of thyroid hormones
T3 and T4
iodinated derivatives of tyrosine, T3 active
hypothyroidism
result from insufficient dietary iodine or ingestion of goitrogens (in staple foods)
thyroid peroxidase
1) incorporate iodide into thyroglobulin protein
2) condenses residues within TG to form T3 or T4
release of thyroid hormones
iodinated TG taken into thyroid cells, fuse with lysosomes, TG broken down, release of free thyroid hormones into circulation (T4 dominant)
deiodination
T4 de-iodinated to generate active T3
de-iodinate T3 to T2 (inactive)
can activate and deactivate
type 1 deiodinase
contributes significantly to circulating T3 conc
kidney, liver, thyroid gland
how are thyroid hormones carried in the blood?
3 proteins
1) thyroid-binding globulin
2) thyroid-binding pre-albumin
3) albumin
T4 bound more tightly (long plasma half life)
goitrogens
competitively inhibit iodide uptake by the thyroid gland
type 2 deiodinase
convert T4 to T3 for local tissue use
brain, pituitary, brown adipose tissue
type 3 deiodinase
operates exclusively on inner ring to inactivate thyroid hormones
thyroid stimulating hormone (TSH)
from pituitary, acts on thyroid gland
regulates TH levels through negative feedback
T4 travels to pituitary to become T3
Elevated TSH levels indicate hypothyroidism, whereas levels are low in hyperthyroidism. Why would this be the case?
TSH levels are controlled by negative feedback – lack of negative feedback, not producing thyroid hormone, there is no negative feedback to regulate TSH > elevated TSH
differentiation of tissues in TH
type 1 deiodinase altered during fasting, but not type 2, so brain and pituitary can still function
thyroid nuclear receptors (TR)
binds T3 in the nucleus, already bound to TREs as a heterodimer with RXR
thyroid hormone response elements (TREs)
DNA sequences in the control regions of target genes
usually found in pairs
TR must select TREs to regulate
heterodimers for TREs
in the presence of T3, TR-RXR heterodimers bind to TREs
binding of T3 leads to recruitment of co-activators, promoting transcription
TH in regulation of lipids
Thyroid hormone stimulates fatty acid synthesis by enhancing expression of the genes involved in this process
enhances lipolysis
substrate cycling
increase by hyperthyroidism, hypo decreases
carbohydrates and TH
glycolysis and gluconeogenesis stimulated by TH
increase substrate cycling
proteins and TH
hyperthyroidism: increase in mRNA synthesis, protein turnover
overall effect of elevated T3 is catabolic
goiter
enlargement of thyroid gland, iodine deficiency
low plasma levels TH > increased TSH > stimulates hyperplasia > goiter
iodine deficiency
low iodine content in soils in flooded areas, exposed to runoff etc
rich in seafood
although T3 can promote anabolic and catabolic processes, the overall effect is
catabolic
