(L12) Hormonal control of metabolism

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What are hormones?
Chemical messengers that regulate and coordinate metabolic activity
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Endocrine hormones
Produced in one tissue (gland) and travels via blood to reach target cell, which has a receptor for that hormone, stored in vesicles in endocrine cell, secreted into plasma when needed
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Paracrine hormones
Produced in one cell, travels short distances to reach neighbouring cell, which has a receptor for that hormone
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Autocrine hormones
Produced in cell which is also the target cell for that hormone, travels via extracellular matrix
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What is a hormone cascade?
A hormone is produced by a gland (e.g. the hypothalamus) which triggers the release of other hormones from other glands
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What are the 3 types of endocrine hormones?
Steroid, peptide/protein and amino acid derived (catecholamines)
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What do they differ in?
Solubility, mechanism of action and speed of action
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What are steroid hormones?
Lipid soluble, basic steroid structure, slow response hormone, alters proportions of specific proteins in a cell
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Describe the mechanism of a steroid hormone
Transported in blood bound to specific transport proteins, transport protein binds to receptor on cell surface, hormone enters target cell, bind to specific receptors within cell (if binds to cytosol, whole complex moves into nucleus)
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Once the steroid hormone is inside the nucleus, what happens?
Hormone-receptor binds to specific regions of DNA (response elements) and they influence transcription
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What are peptide and catecholamine hormones?
Small molecules (proteins, peptides or amino acid derivatives), water soluble, transported free form in blood, rapid response hormone
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Describe the mechanism of a peptide or a catecholamine hormone
Transported in blood to target cell, binds to cell surface but does not enter cell, initiates response via secondary messengers, influences activity of proteins already in the cells
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What are peptide and catecholamine receptors?
Transmembrane proteins with distinct domains: A ligand binding domain to interact with hormone, transmembrane domains crossing the membrane
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What does binding of a ligand to the receptor do?
Induces a conformational change which results in either activation of intrinsic enzyme activity or interaction with other proteins to effect enzyme activity
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What is the receptor that activates intrinsic enzyme activity?
Tyrosine kinase
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What is the receptor that interacts with other proteins to effect enzyme activity?
G protein linked receptor
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What is the effect of the binding to a peptide and catecholamine receptor?
Induces a secondary messenger within cell, the secondary messengers activate a phosphorylation cascade initiated by protein kinases which phosphorylate Ser or The residues on existing cell proteins
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What does phosphorylation of specific proteins do?
Can activate or inactivate them depending on the protein
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Give a few examples of secondary messengers
cAMP, IP3, diacylglycerol (DAG), PIP3, and calcium ions
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What is the G in G linked short for?
Guanosine nucleotide-binding proteins
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How many subunits does the G-protein linked receptors have?
3 Subunits (a b and g- a binds to GTP)
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What happens when the protein bind to the G linked protein receptor?
Changed shape in intracellular part of receptor molecule, G protein interacts with the receptor which induces a conformational change in the a subunit, replacement of GDP with GTP, a-subunit also interacts with target enzyme
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What types of G protein can there be?
Stimulatory (Gs, Gq) or inhibitory (Gi) depending on whether the a-subunit is stimulatory or inhibitory (as,aq or ai)
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Name a target of the Gas protein
Adenylate cyclase
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Describe the G protein activation of adenylate cyclase and the PKa pathway
ATP converted to cAMP as secondary messenger, activates protein kinase A (PKa), PKa normally found in inactive form, cAMP activates it, active PKa catalyses phosphorylation of specific proteins, activating or inactivating them
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How is PKa activated?
PKa has 4 subunits (2 regulatory and 2 catalytic) which are non-active, 4 cAMP bind to the two regulatory subunits which causes a conformational change causing them to dissociate from catalytic subunits, which then become active
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How does the cAMP cause the subunits to dissociate?
The conformational change due to the binding weakens the bonds between subunits
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What happens to the catalytic subunits of the PKa?
They are now active in the cytosol, ready to go and interact with other proteins and cause phosphorylation
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What receptors are involved in G protein activation of phospholipase C and the PKc pathway?
Adrenergic receptors
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What are the 2 types of adrenergic receptors?
Alpha and beta, which activate different pathways
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What is the beta adrenergic receptor involved in?
Energy metabolism
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What is the alpha adrenergic receptor involved in?
Stimulating the heart (fight or flight)
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Where is phospholipase C found?
On the cytoplasmic side of the cell membrane
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What is phospholipase C?
The target of the Gqa which is released from the Gq protein (activator), phospholipase C converts the 4,5-bisphosphate form of the phospholipid PIP2 to IP3 and diacylglycerol (DAG), which are both secondary messengers
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Once phospholipase C has converted PIP2 into IP3 and DAG, what happens?
IP3 binds to an IP3 receptor on the endoplasmic reticulum membrane, opening up an ion channel to release Ca ions into cytoplasm, DAG activates PKc in membrane/ cytoplasm, ca ions used as cofactor
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Briefly describe tyrosine specific kinases
Transmembrane receptor proteins, insulin receptor, when ligand binds there is a conformational change, becomes tyrosine kinase, phosphorylates itself and other proteins on Tyr residues, initiates cascades
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Which cascades does tyrosine specific kinases initiate?
One via PIP3 and protein kinase B (PKB) and one via Ras and MAP kinase
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Briefly describe the PIP2-PKB cascade
Insulin responsive substrates are activated by receptor tyrosine kinase, they bind and activate enzyme PI-3K, which forms PIP3 from PIP2 in membrane, PIP3 attracts PKB which binds and is also activated by phosphorylation by PDK1
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PIP2-PKB cascade continued
Active PKB is then able to phosphorylate specific proteins modifying their activity, glyscogen sythase kinase 3 (GSK3) and phosphoprotein phosphatase 1 (PP1) are activated by phosphorylation
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What does activation of GSK3 and PP1 cause?
They phosphorylate other proteins and also initiate control of gene expression
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What are the function of insulin responsive substrate?
Binds and activates the enzyme PI-3K which forms PIP3 from PIP2 in the membrane, PIP3 attracts PKB which (when bound to PIP3) is activated by phosphorylation by PDK1, active PKB is then able to phosphorylate other proteins and modify their activity
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What else does the IRSs do?
Phosphorylate other proteins (Raf, MEK, ERK) which influence gene expression
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Other cards in this set

Card 2

Front

Endocrine hormones

Back

Produced in one tissue (gland) and travels via blood to reach target cell, which has a receptor for that hormone, stored in vesicles in endocrine cell, secreted into plasma when needed

Card 3

Front

Paracrine hormones

Back

Preview of the front of card 3

Card 4

Front

Autocrine hormones

Back

Preview of the front of card 4

Card 5

Front

What is a hormone cascade?

Back

Preview of the front of card 5
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