ParaThyroid Hormone Synthesis,Storge Secretion and Transportation

TOTAL ParaThyroid Hormone Synthesis,Storge Secretion and Transportation INFORMATION

1. parathyroid Hormone Synthesis, Storge ,Secretion and Transportation ParaThyroid Hormone Synthesis,Storge Secretion and Transportation P rasented B y Gutti.Pavan Msc -I Biochemistry The Institute of Science 1

2. Hormones Hormone : A chemical substance produced in the body that controls and regulates the activity of certain cells or organs. Many   Hormones   aresecretd by special glands Hormones are the body's chemical messengers and are part of the Endocrine system. 4/5/2018 Parathyroid Hormones 2

3. TYPES OF HORMONES Hormone class Components Exmples Amine Hormone Amiino acids with modified groups Adrenailne , thyroxin Proteine Hormone Long chian of linked Amino acids ADH , insulin Steroid Hormone Derived from the lipid cholesterol Cortisol,aldosterone , estrogen Peptide Hormone Short chian of linked Amino acids Glucagon , prolactin ,ACTH Parathyroide Hormone 4/5/2018 Parathyroid Hormones 3

4. Parathyroid Hormone (PTH) Parathyroid hormone is secreted from four parathyroid glands, which are small glands in the neck, located behind the thyroid gland Parathyroid Hormones is secreted by the chief cells of the parathyroid glands as polypeptide containg 84 amino acids . It acts to increase the concentration of calcium (Ca 2+ ) in the blood.  is important in  bone remodeling , which is an ongoing process in which  bone tissue  is alternately  resorbed  &  rebuilt over time. 4/5/2018 Parathyroid Hormones 4

5. PTH Parathyroid hormone regulates calcium levels in the blood, largely by increasing the levels when they are too low. It does this through its actions on the   kidneys , bones and  intestine : Bones – parathyroid hormone stimulates the release of calcium from large calcium stores in the bones into the bloodstream. This increases bone destruction and decreases the formation of new bone.   Kidneys – parathyroid hormone reduces loss of calcium in urine. Parathyroid hormone also stimulates the production of active vitamin D in the kidneys.   Intestine – parathyroid hormone indirectly increases calcium  absorption  from food in the intestine, via its effects on vitaminD   metabolism . 4/5/2018 Parathyroid Hormones 5

6. Parathyroid Hormone chemical structure 4/5/2018 Parathyroid Hormones 6

7. Parathyroid Hormone Synthesis Serum PTH concentrations are dependent upon the release of PTH stored in secretory granules within the parathyroid gland and by the synthesis of new PTH. Ca 2+ , phosphorus, and vitamin D metabolites play a role in regulating PTH release and synthesis 4/5/2018 Parathyroid Hormones 7

8. Bio Synthesis PTH of Flow Chart Parathyroid hormone (PTH) is a polypeptide of 84 amino acids that is synthesized and secreted by the parathyroid glands . The hormone acts on the target organs, bone and kidney, to promote the flow of calcium into the extracellular fluid . The secretion of PTH, in turn, is regulated by the concentrations of calcium in blood and extracellular fluid, thus maintaining calcium homeostasis . In our studies of the factors controlling the synthesis and release of PTH, we identified a biosynthetic pathway for the hormone that involves its formation via two sequential proteolytic cleavages from a larger biosynthetic precursor . The initial product synthesized in parathyroid gland slices in vitro or by translation of parathyroid gland mRNA in cell free systems is pre- propara thyroid hormone (Pre- ProPTH ) of 115 amino acids . This initial prehormone , either during growth of the nascent chain or within I min of completion of synthesis, is converted to an intermediate precursor, proparathyroid hormone ( ProPTH ) of 90 amino acids, by removal of the amino-terminal sequence of 25 amino acids. After a delay of -15 min, ProPTH undergoes a second proteolytic cleavage, resulting in the removal of the amino-terminal sequence of six amino acids, with the resultant formation of PTH,the major hormonal product stored in and secreted from the parathyroid gland 4/5/2018 Parathyroid Hormones 8

9. BIOSYNTHESIS OF PARATHYROID HORMONE The biosynthesis of precursor and secretory forms of parathyroid hormone ( PTH ). Within the nucleus, transcription of the gene encoding PTH is followed by processing of the pre-mRNA through removal of intervening sequences. The mature mRNA leaves the nucleus and attaches to polyribosomes in the cytoplasm. The signal or pre-sequence of the hormone then binds to a signal recognition particle that interacts with a docking protein on the membrane of the endoplasmic reticulum, facilitating entry of the nascent peptide into the cisternae . The signal sequence is removed, leaving the precursor proPTH . The NH 2 -terminal hexapeptide of this molecule is then removed in the Golgi apparatus, and the mature hormone, PTH 1–84, is packaged into secretory granules 4/5/2018 9 Parathyroid Hormones

10. BIOSYNTHESIS PTH 4/5/2018 10 Parathyroid Hormones

11. PTH storage & located 4/5/2018 11 Parathyroid Hormones

12. PTH secretion Secrete parathyroid hormone Humoral stimuli Most important regulator of Ca2+ homeostasis of the blood Hypercalcemic hormone 4/5/2018 12 Parathyroid Hormones

13. PTH secretion 4/5/2018 13 Parathyroid Hormones

14. 4/5/2018 14 Parathyroid Hormones

15. Difference between High (Ca 2+ ) and low (Ca 2+ ) 4/5/2018 15 Parathyroid Hormones

16. PTH Tranasport The two most important hormones for maintaining calcium levels in the body are  parathyroid hormone (PTH)  and  1,25(OH) 2 D  (the  active form of vitamin D ). The major regulator is PTH, which is part of a negative feedback loop to maintain [Ca ++ ] ECF  (see  Humoral regulation ). PTH secretion is stimulated by hypocalcemia , and it works through three mechanisms to increase Ca ++  levels: PTH stimulates the release of Ca ++  from bone, in part by stimulating  bone resorption . PTH decreases urinary loss of Ca ++  by stimulating  Ca ++   reabsorption . PTH indirectly stimulates  Ca ++  absorption  in the small intestine by stimulating synthesis of 1,25(OH) 2 D in the kidney 4/5/2018 16 Parathyroid Hormones

17. Homeostasis 4/5/2018 17 Parathyroid Hormones

18. Bones, Kidneys ,Intestine Bones :   parathyroid hormone stimulates the release of calcium from large calcium stores in the bones into the bloodstream. This increases bone destruction and decreases the formation of new bone.   Kidneys : parathyroid hormone reduces loss of calcium in urine. Parathyroid hormone also stimulates the production of active  vitamin d  in the kidneys.   Intestine: parathyroid hormone indirectly increases calcium  absorption  from food in the intestine, via its effects on vitamin D  metabolism . 4/5/2018 18 Parathyroid Hormones

19. Summary PTH increases blood calcium concentrations when calcium ion levels fall below normal. First, PTH enhances reabsorption of calcium by the kidneys; it then stimulates osteoclast activity and inhibits osteoblast activity. Finally, PTH stimulates synthesis and secretion of calcitriol by the kidneys, which enhances Ca2+ absorption by the digestive system. 4/5/2018 19 Parathyroid Hormones

20. Diseases and Disorders of the Parathyroid When the parathyroid releases too much or too little PTH, it adversely affects your body in a variety of ways. Below are common diseases and disorders associated with the parathyroid glands 4/5/2018 20 Parathyroid Hormones

21. Hyperparathyroidism   Hyperparathyroidism:  CAUSES: The most common disease of parathyroid glands is hyperparathyroidism, which is characterized by excess PTH hormone, regardless of calcium levels. In other words, the parathyroid glands continue to make large amounts of PTH . SYMPTOMS: Bone pain , Muscle weekness , Long bone fractures , kidneystone Treatment : Optimize the levels of serum calcium and phosphate ions control of PTH and vitamin D 4/5/2018 21 Parathyroid Hormones

22. Hypoparathyroidism CAUSES Hypoparathyroidism  is the combination of symptoms due to inadequate parathyroid hormone production. This leads to decreased blood levels of calcium ( hypocalcemia ) and increased levels of blood phosphorus ( hyperphosphatemia ). SYMPTOMS: Drcreased ca ions levels in blood, sensitive nerves , uncontrollable spasms of the limbs Treatment : daily calcium and vitamin D supplements 4/5/2018 22 Parathyroid Hormones

23. Osteoporosis CAUSES: Osteoporosis:  When one of the parathyroid glands is overactive, it releases too much PTH hormone. This causes your bones to release calcium constantly into the blood stream. Without enough calcium in your bones, they lose their density and hardness. SYMPTOMS: Bone pain or tenderness neck or lower back pain due to fractures , stoped posture Treatment : biphosphonates ,vitamin D 4/5/2018 23 Parathyroid Hormones

24. REFERENCE Books: Harpers lllustrated Biochemistry-Robert . k.Murry , Daryl.k.Granner JOURNALS : The mechanism of parathyroid hormone action on calcium reabsorption by the distal tubule. Bouhtilauy , lajeunesse .- Endocrine society ( PUBMED) NCBI The Regulation of Parathyroid Hormone Secretion and Synthesis Published in final edited form as: J Am Soc Nephrol . 2011 February ; 22(2): 216–224. doi:10.1681/ASN.2010020186. parathyroid interaction: implications in chronic kidney disease-kidney international journal Volume77, issue 4, febuary 2010 , pages 292-298 Biosynthesis of Parathyroid Hormone The New England journal of Medicine journal September 14, 1978 ,DOI : 1110.1056 /NEJM 19780914299110 The Regulation of Parathyroid Hormone Secretion and Synthesis Journal of the American ociety of nephrology Published online before printDecember 16, 2010, doi:10.1681/ASN.2010020186 Stimulation of ovine placental transport of calcium and magnesium by mid‐molecule fragments of human parathyroid hormone‐related protein The physiological society- AD.Care , SK.Abbas , afirst published : 1 july 1990 https://doi.org/10.1113/expphysiol.1990 INTERNET https://en.wikipedia.org/wiki/Parathyroid_hormone http://emedicine.medscape.com/article/2089334-overview http://www.parathyroid.com/hypoparathyroidism.htm http://www.parathyroid.com/parathyroid-function.htm https://www.endocrineweb.com/conditions/parathyroid/parathyroid-function https://www.hormone.org/hormones-and-health/hormones/parathyroid-hormone 4/5/2018 24 Parathyroid Hormones