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52 Cards in this Set
- Front
- Back
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What are the chemical names for the thyroid hormones T3 and T4?
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T3: Triiodothyronine
T4: Thyroxine |
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Very briefly describe the structure of the thyroid follicles.
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Thyroid follicles have a central luminal region filled with colloid, surrounded by a layer of follicular epithelial cells. These cells concentrate iodide, produce thyroglobulin and T3 and T4
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What is the limiting step of hormone synthesis in normal thyroid?
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The intake of iodine by the follicular cells
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What enzyme is involved in the iodine pump mechanism?
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ouabain-sensitive sodium/potassium ATPase
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What is the approximate normal thyroid to serum iodide ratio?
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The thyroid concentrates iodine 25x more than the serum.
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What are the effects of ClO4- and SCN-?
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-They inhibit the ouabain-sensitive sodium/potassium ATPase which uptakes iodine by the follicular cells
-SCN- are sometimes used to unmask the details of thyroid deficiencies |
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What is iodinated by the reaction involving hydrogen peroxide, iodide ion and thyroid peroxidase?
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tyrosyl residues on thyroglobulin
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What is the function of thyroglobuilin?
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It is the storage form of thyroid hormones T4 and T3
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What is special about the structure of Thyroglobulin?
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Acts as a template to line up iodinated tyrosyl residues allowing for coupling reactions.
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To what proteins are T3 and T4 bound while in circulation?
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-thyroxine binding globulin (TBG) (75% T4 and 50% T3)
-thyroxine binidng prealbumin (TBPA)(20% of T4 and no T3) also known as transthyretin -albumin (50% T3 and 5% T4) |
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What happens to most of the T4 in target tissues?
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T4 is converted into T3 by the enzyme 5'deiodinase
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What is reverse T3?
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inactivated form, formed usually in largest amount in chronic diseases, starvation and in the fetus
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Where is the thyroid hormone receptor located?
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The thyroid receptor is located in the nucleus
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To what superfamily of receptors does it belong?
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is a member of the steroid receptor superfamily (even tho thyroid hormones are not steroids)
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What are the general effects of thyroid hormones?
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-Anabolic for most tissues (Stimulates oxidation in many tissues)
-most effects have slow onset -generally increase production of DNA, RNA, epidermal growth factor, nerve growth factor and increase growth hormone synthesis -T3 exerts a general thermogenic effect |
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Goiter?
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Goiter is disorder caused by desensitized TSH receptors, which cause hypertrophy of the thyroid gland, and subsequently excess thyroid hormone production.
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Graves’ disease?
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Graves’ disease is hyperactivity caused by a the binding of thyroid stimulating antibody to TSH receptors.
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Cretinism?
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Neonatal thryroid hormone deficiency, retardation of the brain maturation and growth
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myxedema
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Hypothyroidism in adults. Results slow speech, slow reflexes, poor memory, fatigue and constipation
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How do antithyroid drugs work?
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Antithyroid drugs act by inhibiting the uptake of Iodide ions by the thyroid follicle cells (oganification of iodine)
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What is (131)^I used for?
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ablation of thyroid cells to treat hyperthyroidism.
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Name 3 types of bone cells
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Osteoblasts, Osteoclasts, Osteocytes
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Which of the bone cells add calcium to bones, and which degrade bone, removing calcium?
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Osteoblasts build up bones by adding calcium minerals.
Osteoclasts degrade bone, removing calcium. |
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What is the mechanism by which bone is cut by these cells?
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Osteoclasts secrete collagenase, other enzyme and acids to tunnel through mineralized bone, forming cavities that are invaded by other cells.
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Name the 3 major hormones involved in calcium homeostasis
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Parathyroid hormone (PTH)
Calcitrol Calcitonin |
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Which of the above hormones are peptides?
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PTH
Calcitonin |
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Where is PTH synthesized?
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in the chief cells of the parathyroid gland
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Where is calcitonin synthesized?
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secreted by parafollicular cells of the thyroid gland
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Where is calcitrol synthesized?
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-Kidney and placenta (Synthesis starts in the skin (Vitamin D precursor) then occurs in the liver, and is modified in the kidney)
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What is the effect of PTH upon circulating calcium ion concentrations?
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-rate of PTH secretion an serum PTH concentration vary inversely with the free calcium ion concentration
- Stimuation by serum calcium ions activated release of IP3 causing calcium concentration to rise (increase in cAMP and modulation of PTH secretion) |
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What is the effect of calcitonin upon circulating calcium ion concentrations?
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Decreases the activity and number of osteoclasts, inhibiting release of calcium from bones. (decreases circulating calcium)
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What is the effect of calcitrol upon circulating calcium ion concentrations?
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Responsible for translocation of calcium across the intestinal membrane against the concentration gradient. (increases circulating concentration).
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What are islets of langerhans?
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Collections of cells in the pancreas that fulfill the endocrine function and play an important role in maintaining homeostasis
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what percentage of the organ do the islets of langerhans constitute?
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They compose 1-2% of the organ.
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What are the main cell types in the islets and what do they secrete?
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They are composed of α,β,δ and F cells which secrete insulin (β cells) glucagons (α cells), somatostatin and pancreatic peptide.
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Briefly describe the structure of insulin
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Insulin is a heterodimeric structure with an α chain of 21 amino acids and a β chain of 30 amino acids. They are held together by 2 disulfide bonds. There is also an additional disulfide bond on the a chain. Insulin is very close in structure to porcine and bovine.
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What reactions take place between the synthesis of preproinsulin to the final cleavage in the secretory granules?
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1) Preproinsulin has signal peptide sequence removed= proinsulin.
2) Proinsulin is folded and disulfide bridges are made. 3)Proinsulin is packed into secretory granules and forms complex w/ zinc 4) Proinsulin is converted to insulin and C peptide by cleavage at 2 points. which are released into the portal circulation. |
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What are the contents of the secretory granules that are released?
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Insulin and C peptide
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Comment briefly on the magnitude of the effects that insulin has on cells.
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-Anabolic effects, producing fuel storage, growth and modification of many tissue functions
-Stimulates uptake of glucose into the cells (except for liver, brain and erythrocytes). |
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Name 3 enzyme activities that are increased and three that are decreased by insulin action.
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Activities increased by the action of insulin:
Glucokinase activity Phosphofructokinase activity Pyruvate kinase activity Acetyl CoA carboxylase activity HMG-CoA reductase activity Glycogen synthase activity Protein synthesis Activities decreased by the action of insulin: G6P phosphatase PEP-carboxykinase F1,6-bisphosphotase Protein degradation |
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Very briefly describe the location and structure of the insulin receptor.
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Heterotetrameric w/ 2 α subunits and 2 β subunits.
-The α subunits are outside plasma membrane, and are joined by a disulfide bond. -The β subunits extend from the cytoplasm through plasma mebrane, and are joined to the α subunits by disulfide bond but not each other. |
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What reaction does the insulin receptor perform upon itself when insulin binds?
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When insulin binds, it carries out auto-phosphorylation of the beta chains by a protein tyrosine kinase reaction--> various chemical signals (IRS-1, SHPT2, GRB-2)
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What cells are not stimulated by insulin to transport glucose?
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Liver, brain and erythrocytes are not stimulated
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In terms of insulin receptors, what is “down regulation?” In what circumstances are cells “up regulated?”
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"Down regulation” is the reduction of insulin receptors on the surface of a cell. This happens by internalization when insulin binds.
Cells are upregulated when they have not been exposed to significant amounts of insulin and have an increased number of insulin receptors |
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Is the glucose transporter the same or different than the insulin receptor?
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The glucose transporter is very different than the insulin receptor. Glucose transporters are facilitated transporters where insulin receptors are complex tetramers that trigger a cascade of reactions.
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What is the effect that glucacon has on insulin secretion and vice versa?
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Glucagon is an insulin antagonist. Insulin suppresses glucagon secretion and glucagon stimulates insulin release.
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What general types of effects does glucagon have?
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-Catabolic effects which cause breakdown and usage of energy stores.
-Glucagon generally activates a pathway for the phosphorylation of various enzymes. Activities increased by the action of glucagon: Glycogen breakdown Gluconeogenesis Ketogenesis Lipolysis (in adipose tissue) Activities decreased by the action of glucagon: Glycogen synthesis |
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What is the general type of receptor used with glucagon?
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The glucagon receptor is a G-protein receptor.
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Give a very brief description of the structure of glucagon.
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Glucagon is a 29 AA straight-chain poypeptide chain.
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What are two locations where somatostatin is secreted?
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Somatostatin is secreted by the D cells in the pancreas as well as the hypothalamus.
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What is the function of somatostatin?
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Its function is to inhibit growth hormone secretion, as well as insulin and glucagon secretion. Also blocks the release of TSH, supresses gall bladder contraction and supressed the process of food by the gastrointestinal tract
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What is somatostatin used for clinically?
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Somatostatin can be used to treat gastric bleeding (hemorrhaging), to prevent acromegaly (too much growth hormone) and to prevent pancreatitis.
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