iodine Thyroid hormones are synthesized from the amino acid tyrosine The synthesis requires the iodination of tyrosine molecules and the combination of two iodinated tyrosine residues T3 ID: 927770
Download Presentation The PPT/PDF document "An important component in the synthesis ..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Slide2Slide3Slide4An important component in the synthesis of thyroid hormones is
iodine
. Thyroid hormones are synthesized from the amino acid tyrosine.
The synthesis requires the iodination of tyrosine molecules and the combination of two iodinated tyrosine residues.
T3
is frequently considered the
physiologically active hormone,
and consequently the one on which most athletes and bodybuilders focus their energies on.
T4
is a
prohormone
and a
reservior
for the most active thyroid hormone (T3).
T4
is converted as required in the tissues by
Iodothyronine
deiodinase
.
Slide5Thyroglobulin (Tg)
is a dimeric protein produced by the follicular cells of the thyroid and used within the thyroid gland.
(Tg) is a precursor of thyroid hormones which are produced when thyroglobulin's tyrosine residues are combined with iodine and a protein is subsequently cleaved..Each thyroglobulin molecule contains approximately 100-120 tyrosine residues, but only (20) of these are iodinated by thyroperoxidase in the folliculear colloid.
Therfore
,each
Tg
molecule form only approximately
10
thyroid hormone molecules.
Slide6Slide7Slide8Slide9Slide10Slide11The nature of the enzyme thyroperoxidase
Oxidation of iodide to active iodine, iodination of tyrosine residues and coupling of iodotyrosines are catalyzed by a heme-containing particulate bound peroxidase called thyroperoxidase which requiresH2O2 for its activity.
Iodine trapping:
The thyroid gland concentrates iodine by
actively and selectively transporting
it from the circulation. The transport mechanism is called as iodide trapping or iodide-pump.
The iodide trapping is done :_
1-
Against electrical gradient.
2-
Against concentration gradient.
Iodide transporter pump is located in the basal plasma membrane in association with Na+-K+ dependent ATP
ase
and requires a simultaneous activity of the
soduim
pump.
Energy is provided by hydrolysis of ATP followed by a K+ influx and Na+ efflux.
Slide12Iodide Metabolism
Concentration of iodide (I ¯ ) :-
The thyroid along with other epithelial tissue mammary gland, salivary and stomach is able to concentrate I ¯ against electrochemical gradient.
Oxidation of I ¯ :-
The thyroid is only tissue that can oxidize (I ¯) to higher valence state (I+) .This step involves a heme-containing
peroxidas
and occurs at the luminal surface of the follicular cell.
Iodination of Tyrosine:-
Oxidized iodide reacts with tyrosyl residues in thyroglobulin .The 3 position of the aromatic ring is iodinated first and then the 5 position to form MIT and DIT, this occurs within seconds in luminal thyroglobulin.
Coupling of
iodotyrosyls
:-
The coupling of two DIT molecules to form T4 or of MIT and DIT to form T3 occurs within the thyroglobulin molecule.
Slide13Plasma transport
Most of the thyroid hormone circulating in the
blood is bound to transport proteins. Only a very small fraction of the circulating
hormone
is free (unbound) and biologically active
Slide14T3 and T4
in plasma are carried by tow specific plasma proteins: 1-Thyroxine binding globulin (TBG) .
2-Thyroine binding prealbumin
(TBPA).
When binding capacity of the above two
carreir
proteins is
saturated,then
they can be bound to serum albumin also.
Slide15Slide16Control of TSH Secretion
TSH stimulates the synthesis and release of thyroid hormones from the thyroid gland. The secretion of TSH from the anterior pituitary gland is controlled by:-
1-
Circulating concentrations of thyroid hormones.
Thyroid hormones reduce TSH secretion by negative feedback.
2-
Thyrotrophic-releasing hormone (TRH).
TSH secretion is stimulated by TRH, produced in the hypothalamus .
Slide17Slide18Slide19Slide20Thyroid Function Tests
1- The concentration of TBG and its degree of saturation with T3 and T4.
2-
Concentration of free T3 and T4.
3-
The status of hypothalamus and anterior pituitary with their respective outputs of TRH and TSH .
4-
The response of the pituitary to TRH and response of the thyroid to TSH .
Slide21Slide22Slide23Slide24Slide25Hypothyroidism
Slide26Hypothyroidism
is the result from any condition that results in thyroid hormone deficiency.
Iodine deficiency: Iodide is absolutely necessary for production of thyroid hormones; without adequate iodine intake, thyroid hormones cannot be synthesized.
Primary thyroid disease
:
Inflammatory diseases of the thyroid that destroy parts of the gland are clearly an important cause of hypothyroidism.
Congenital hypothyroidism
: May be due to absence of the thyroid gland (
athyreosis
) or may occur
secondarly
to defects of thyroid hormone synthesis.
Secondary hypothyroidism
: Results from pituitary or hypothalamic disease that produce a deficiency of TSH .
Slide27Laboratory Evaluation of Hypothyroidism
Hypothyroidism may be suspected by symptoms and signs, but the diagnosis needs to be confirmed biochemically.
Free T4 levels are low, T3 levels may within normal limits. TSH is raised in primary hypothyroidism which is the most common cause of hypothyroidism. If TSH is not elevated, it is important to look for pituitary or hypothalamic disease.
In older individuals, biochemical screening for hypothyroidism with a single TSH is recommended.
Thyroid autoantibodies suggest Hashimoto's thyroiditis
LDL may be elevated
Slide28Hyperthyroidism
Slide29