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Metabolic Endocrinology > ppwt 3 > Flashcards

ppwt 3 Flashcards

1
Q

what is the process of Hormone action

A

extracellular signal molecule binds to receptor protein -> intracellular signalling protein -> target protein

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2
Q

what are the 2 types of recptors

A

pathways with cell surface receptor and pathways with intracellular receptor

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3
Q

where is the receptor found for
hydrophilic hormones
hydrophobic hormones

A

hydrophilic : cell surface
hydrophobic: intracellular receptor

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4
Q

what are the rules and exceptions for lipids hormones prostaglandins and leukotrienes

A

they have cell surface recptors instead of nuclear reco

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5
Q

what is the basic structure of a cell surface recptor

A
  1. ectodomain - hormone bind, rich in cysteine residues
  2. hydrophobic transmenbraine - in th elipid billayer
  3. cytoplasic domain - relays signal and induce a signaling cascade
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6
Q

true or false
does cytoplasmic domain indeuce a signaling cascade

A

true

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7
Q

what are the 3 protiens that are modulated by phosphorylation

A

serine, threonine and tyrosine

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8
Q

explain the process by which proteins are modulated by phosphorylation

A
  1. an inactive protein is activated by protein kinase and ATP->ADP. Their OH will be transformed as P
  2. the activated protein will serve as enzymes for other activation of protein
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9
Q

which phosphorylated amino acids are more abundant

A

serine and threonine are more abundant than tyrosine

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10
Q

what are the 3 types of cell surface receptors

A
  • G protein coupled receptor (GPCR)
  • Tyrosine kinase receptor (RTK)
  • serine threonine kinase receptor (RSTK)
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11
Q

explain the GPCR

A
  1. epinephrin binds to its specific receptor
  2. GDP is replaced to GTP in the Gs coupled receptor
  3. Gs alpha binds to adenylyl cyclase
  4. adenylyl cyclase catalyses the formation of cAMP
  5. cAMP activates PKA
  6. pka will cause a cellular response to epinephrine
  7. with the enzyme cyclic nucleotide phosphodiesterase cAMP is degraded and there is no PKA activation
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12
Q

what are the 2 parts of PKA

A

catalytic subunit and the regulatory subunit

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13
Q

what happens to pka when 4 camp binds to it

A

the catalytic subunit cleft will be available

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14
Q

explain the pathway of signal control - desensitization and desensitization cycle

A
  1. binding of epinephrine to beta-adrenergic receptor triggers dissociation of Gsbeta gamma from Gs alpha
  2. Gsbeta gamma recruits Bark and it phosphorylates SER residues at the carboxyl terminus of the receptor
  3. B arrestin (Barr) binds to the phosphorylated carboxyl-terminal domain of the receptor
  4. receptor arrestin complex enters the cell by endocytosis
  5. arrestin dissociates, receptor is dephosphorylates and returned to cell surface
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15
Q

explain what is the function of Gs alpha?

A

activates adenylate cyclase

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16
Q

explain what is the function of Gis alpha?

A

inhibits adenylate cyclase

17
Q

explain what is the function of Gqs alpha?

A

activates phospholipase C

18
Q

explain what is the function of Gos alpha?

A

activates ion channels

19
Q

explain what is the function of G12/13 alpha?

A

regulate actin cytoskeleton

20
Q

Explain the pathway of GPCR signalling through IP3 and Ca

A
  1. hormone binds to a specific receptor
  2. the occupied receptor causes gdp-gtp changes in the Gq complex
  3. Gqalpha with bound GTP moves to Phosphilipase C and activates it
  4. active PLC cleaves PIP2 to IP3 and diacylglycerol
  5. IP3 binds to a specific receptor gated Ca2+ channels, releasing sequestered Ca2+
  6. diacylglycerol and Ca2+ activate protein kinase C
  7. phosphorylation of protein kinase C produces some of the cellular response to the hormones
21
Q

what are the 2 functions of tyrosine kinase coupled receptors

A
  1. receptors with intrinsic kinase activity
  2. receptors that recruit kinase
22
Q

what are the structure of a receptor with intrinsic kinase activity

A

hetero-tetrameric structure (2 alpha and 2 beta chains held together by sulfide bonds)

23
Q

what are the 2 majors pathways of intrinsic kianse activity

A

MAPK, PIP3

24
Q

Explain the pathway of insulin signalling through the MAPK pathway

A
  1. insulin receptor binds insulin and undergoes autophosphorylation on its carboxyl-terminal
  2. insulin receptor phosphorylates IRS-1 on its Tyr residues
  3. Grb2 binds t the phosphate of the IRS-1. Sos binds to Grb2 and then to Ras causing GDP release and GTP binding
  4. Activated Ras binds and activates Raf 1
  5. raf-1 phosphorylates MEK on 2 ser residues activating it. MEK phosphorylates ERK
  6. ERK moves to the nucleus and phosphorylates nuclear transcription factors such as Elk1
  7. phosphorylated Elk 1 joins SRF and stimulate the transcription and translating of genes for cell division
25
Q

explain the insulin receptor signaling through PIP3

A
  1. IRS phosphorylated by the insulin receptor activates PI3K. PI3K converts PIP2 to PIP3
  2. PKB bound to PIP3 is phosphorylated and it deactivates GSK3
  3. The inactivation of GSK3 activates GS (glycogen synthase)
  4. synthesis of glycogen from glucose is accelerated
  5. PKB stimulates movement of glucose transporter GLUT 4 from internal vesicles to the plasma membrane increasing the uptake of glucose

Metabolic Endocrinology (9 decks)

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