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An overview of thyroid and insulin hormones, detailing their biosynthesis, storage, release, and biochemical functions. It covers the synthesis of thyroxine (t4) and triiodothyronine (t3) by the thyroid gland, emphasizing the role of iodine and thyroglobulin. The document also explains the metabolic effects of insulin, including its influence on carbohydrate, lipid, and protein metabolism, as well as the mechanism of insulin action and glucose transport. Additionally, it touches on the biochemical functions of catecholamines and their effects on carbohydrate and lipid metabolism. Useful for students studying endocrinology, biochemistry, and related fields, offering a comprehensive look at hormone regulation and metabolic processes.
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Thyroid gland (weighs about 30 g in adults) is located on either side of the trachea below the larynx. It produces two principal hormones — thyroxine (T4; 3,5,3’,5’-tetraiodo thyronine) and 3,5,3’-triiodothyronine (T3) — which regulate the metabolic rate of the body. Thyroid gland also secretes calcitonin, a hormone concerned with calcium homeostasis
Iodine is essential for the synthesis of thyroid hormones. More than half of the body’s total iodine content is found in the thyroid gland
gradient (about 20 : 1). It is an energy requiring process and is linked to the ATPase dependent Na+-K+ pump. Iodide uptake is primarily controlled by TSH. Antithyroid agents such as thiocyanate and perchlorate inhibit iodide transport.
essential step for its incorporation into thyroid hormones. Thyroid is the only tissue that can oxidize I– to a higher valence state I+. This reaction requires H2O2 and is catalysed by the enzyme thyroperoxidase (mol. wt. 60,000). An NADPH dependent system supplies H2O2. TSH promotes the oxidation of iodide to active iodine while the antithyroid drugs (thiourea, thiouracil, methinazole) inhibit
Thyroglobulin (mol. wt. 660,000) is a glycoprotein and precursor for the synthesis of T3 and T4. Thyroglobulin contains about 140 tyrosine residues which can serve as substrates for iodine for the formation of thyroid hormones. Tyrosine (of thyroglobulin) is first iodinated at position 3 to form monoiodotyrosine (MIT) and then at position 5 to form diiodotyrosine (DIT). Two molecules of DIT couple to form thyroxine (T4). One molecule of MIT, when coupled with one molecule of DIT, triiodothyronine (T3) is produced. The mechanism of coupling is not well understood. The details of synthesis of T3 and T4 are given under tyrosine metabolism. As the process of iodination is completed, each molecule of thyroglobulin contains about 6- 8 molecules of thyroxine (T4). The ratio of T3 to T4 in thyroglobulin is usually around 1 : 10
Thyroglobulin containing T4 and T3 can be stored for several months in the thyroid gland. It is estimated that the stored thyroid hormones can meet the body requirement for 1-3 months. Thyroglobulin is digested by lysosomal proteolytic enzymes in the thyroid gland. The free hormones thyroxine (90%) and triiodothyronine (10%) are released into the blood, a process stimulated by TSH. MIT and DIT produced in the thyroid gland undergo deiodination by the enzyme deiodinase and the iodine thus liberated can be reutilized.
Two specific binding proteins—thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA)—are responsible for the transport of thyroid hormones. Both T4 and T are more predominantly bound to TBG. A small fraction of free hormones are biologically active. T4 has a half-life of 4-7 days while T3 has about one day
Triiodothyronine (T3) is about four times more active in its biological functions than thyroxine (T4). The following are the biochemical functions attributed to thyroid hormones (T3 and T4).
activities and increases the oxygen consumption in most of the tissues of the body (exception—brain, lungs, testes and retina).
share of cellular ATP. Na+-K+ ATPase activity is directly correlated to thyroid hormones and this, in turn, with ATP utilization. Obesity in some individuals is attributed to a decreased energy utilization and heat production due to diminished Na+-K+ ATPase activity.
protein synthesis by acting at the transcriptional level (activate DNA to produce RNA). Thyroid hormones, thus, function as anabolic hormones and cause positive nitrogen balance and promote growth and development.
About 40-50 units of insulin is secreted daily by human pancreas. The normal insulin concen tration in plasma is 20-30 U/ml. The important factors that influence the release of insulin from the - cells of pancreas
gastrointestinal hormones.
signal for insulin secretion.
of protein-rich meal that causes transient rise in plasma amino acid concentration. Among the amino acids, arginine and leucine are potent stimulators of insulin release
insulin.
insulin release. In emergency situations like stress, extreme exercise and trauma, the nervous system stimulates adrenal medulla to release epinephrine.
In the plasma, insulin has a normal half-life of 4 - 5 minutes. A protease enzyme, namely insulinase (mainly found in liver and kidney), degrades insulin
Insulin plays a key role in the regulation of carbohydrate, lipid and protein metabolisms.
ingested glucose is utilized to meet the energy demands of the body (mainly through glycolysis). The other half is converted to fat (~ 40%) and glycogen (~ 10%). The net effect is that insulin lowers blood glucose level (hypoglycemic effect) by promoting its utilization and storage and by inhibiting its production. L
muscle (skeletal, cardiac and smooth), adipose tissue, leukocytes and mammary glands. Surprisingly, about 80% of glucose uptake in the body is not dependent on insulin. Tissues into which glucose can freely enter include brain, kidney, erythrocytes, retina, nerve, blood vessels and intestinal mucosa.
activation as well as the quantities of certain key enzymes of glycolysis, namely glucokinase (not hexokinase) phosphofructokinase and pyruvate kinase are increased by insulin. Glycogen production is enhanced by insulin by increasing the activity of glycogen synthetase.
enzymes pyruvate carboxylase, phosphoenol pyruvate carboxykinase and glucose 6 phosphatase. Insulin also inhibits glyco-genolysis by inactivating the enzyme glycogen phosphorylase.
The net effect of insulin on lipid metabolism is to reduce the release of fatty acids from the stored fat and decrease the production of ketone bodies.
providing more glycerol 3-phosphate (from glycolysis) and NADPH (from HMP shunt). Insulin increases the activity of acetyl CoA carboxylase, a key enzyme in fatty acid synthesis.
reduces the release of fatty acids from stored fat in adipose tissue.
synthetase
of amino acids into the cells, enhances protein synthesis and reduces protein degradation.
The binding of insulin to insulin receptors signals the translocation of vesicles containing glucose transporters from intracellular pool to the plasma membrane. The vesicles fuse with the membrane recruiting the glucose transporters. The glucose transporters are responsible for the insulin–mediated uptake of glucose by the cells. As the insulin level falls, the glucose transporters move away from the membrane to the intracellular pool for storage and recycle
Insulin promotes the synthesis of enzymes such as glucokinase, phosphofructokinase and pyruvate kinase. This is brought about by increased transcription (mRNA synthesis), followed by translation (protein synthesis)
Catecholamines cause diversified biochemical effects on the body. The ultimate goal of their action is to mobilize energy resources and prepare the individuals to meet emergencies (e.g. shock, cold, low blood glucose etc.).
increase the degradation of glycogen (glycogenolysis), synthesis of glucose (gluconeogenesis) and decrease glycogen formation (glycogenesis). The overall effect of catecholamines is to elevate blood glucose levels and make it available for the brain and other tissues to meet the emergencies.
breakdown of triacylglycerols (lipolysis) in adipose tissue. This causes increase in the free fatty acids in the circulation which are effectively utilized by the heart and muscle as fuel source. The metabolic effects of catecholamines are mostly related to the increase in adenylate cyclase activity causing elevation in cyclic AMP
epinephrine) increase cardiac output, blood pressure and oxygen consumption. They cause smooth muscle relaxation in bronchi, gastro intestinal tract and the blood vessels supplying skeletal muscle. On the other hand, catecholamines stimulate smooth muscle contraction of the blood vessels supplying skin and kidney. Platelet aggregation is inhibited by catecholamines.