Chapter 8 (Lectures 8-11) Basic Concepts of Metabolism Unit II: Intermediary Metabolism AJG.
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Transcript of Chapter 8 (Lectures 8-11) Basic Concepts of Metabolism Unit II: Intermediary Metabolism AJG.
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Chapter 8 (Lectures 8-11)
Basic Concepts of Metabolism
Unit II: Intermediary Metabolism
AJG
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1 Introduction to metabolism
A. Define metabolism in terms of anabolic and catabolic processes1. Compare, contrast, anabolic & catabolic pathways2. Include the concept and the importance of electron carriers3. Explain why catabolic pathways are considered convergent4. Explain why anabolic pathways are considered divergentB. Explain the importance of cell-cell communication in the regulation ofmetabolism.C. List the 4 different types of receptors and their basic mechanism of actionD. Give examples of the four types of receptors.E. Describe the two second messenger systems( adenylate cyclase) and thephophoinositide systemF. Indicate the receptors, G-protein and effector enzyme in each of thesesystems.G. Indicate what second messenger(s) are produced by activation of adenylatecyclase and phospholipase C.H. Indicate which protein kinase (PKA, PKC) is activated in both systems
Learning objectives: Introduction to metabolism
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Catabolism
• degradation• convergent• “oxidative”
• products:
ATPFADH2
NADHNADPH
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Anabolism
• synthesis• “reductive”• divergent• uses ATP
• products:
NAD+
FADADPNADP+
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Stages of Catabolism
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Stage 1
Stage 2
Stage 3
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Regulation of Metabolism
The pathways of metabolism must be coordinated so that the production of energy or the synthesis of end products meets the needs of the cell.
An efficient communication system is necessary to coordinate the functions of the body.
Regulation depends on:
• intercellular signals
• intracellular signals- signal trasduction
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Intercellular signals
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Extracellular signals are converted to Intracellular
signals
Signal Transduction
OR
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Intercellular signals
Intracellular signals
cAMP
are converted
to an intracellular signal in the
adjacent cell
Enzyme-P
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4 basic types of signal transduction pathways:
1. Steroid receptor
2. Gated ion channel
3. Receptor enzyme (Catalytic receptor)
4. G-protein coupled receptor (GPCR)
produce intracellular 2nd messengers
Receptor-mediated Signal Transduction (Extracellular signals)
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Four general types of receptorsGPCR
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1. Steroid receptor mechanism of signal transduction
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1. Steroid receptor mechanism of signal transduction
mechanism may take hours or days (slow)
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2. Gated ion channel
• receptor linked to ligand or voltage-gated ion channel
• binding of neurotransmitter causes channel to open
• results in rush of ions through ion channel altering membrane potential promoting or inhibiting nerve impulse transmission
• Examples: nicotinic ACh receptors of muscle or nerve and -aminobutyric acid (GABA) and glycine receptors in the CNS
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2. Gated ion channel
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3. Receptor enzyme (Catalytic receptor)
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3. Receptor enzyme (Catalytic receptor)• Transmembrane catalytic receptors that have enzymatic activity as part of their structure
• Enzyme is a tyrosine-specific protein kinase(adds a phosphate to specific tyrosine residues)
• Several cell-surface receptors contain an extracellular domain for binding ligands and an intracellular domain with tyrosine kinase activity
• Example: insulin receptor in which binding of ligand ATP cleavage, autophosphorylation and phosphorylation of specific tyrosine residue in target proteins
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G-protein coupled receptor (GPRC)
produce intracellular 2nd messengers
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• Hormones and neurotransmitters are signals and receptors are signal detectors
• Receptors indicate receipt of a signal through the production a “second messenger” inside the cell
• Second messengers trigger a cascade of intracellular events in response to the binding of a
hormone to its receptor
• Examples: 1. Adenylate cyclase system (cAMP)2. Calcium/phosphatidylinositol system (IP3, DAG, Ca2+)
4. GPCR and Intracellular Second Messengers
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4. Intracellular Second Messengers
• Definition: Second messengers are small molecules produced in the cytoplasm in response to the activation of a cell surface receptor
• Examples :
• cAMP• IP3, DAG, Ca2+
• cGMP• Nitric Oxide (NO)
Second messengers start a cascade of intracellular events (enzyme activation, inhibition) resulting in a specific cellular response
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• Adenylate cyclase sytem:• c-AMP(second messenger)
• Protein kinase A
second messenger systems
Stimulus: epinephrin/norepinephrine or glucagon
Receptors: β-adrenergic receptor or glucagon receptor
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Adenylate cyclase system
• second messenger is cAMP
• cAMP activates protein kinase A
• protein kinase A phosphorylates target proteins
• phosphodiesterase hydrolyzes cAMP to 5’-AMP
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G-protein coupled receptor (GPRC)
produce intracellular 2nd messengers
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• Phosphoinositide system:• Inositol tris-phosphate
• Calcium• Diacylglycerol
• Protein kinase C
G-protein coupled receptor (GPCR)
produce intracellular 2nd messengers
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P
P
Phosphatidylinositol 4, 5-bis-phosphate
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Phosphatidylinositol 4, 5-bis-phosphate (PIP2)
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Phosphatiylinositol-4,5-bis-phosphate (PIP2)
Phospholipase C cleaves PIP2 to
generate IP3 and
DAG
DAG
IP3
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Phospholipase C (PLC) cleaves PIP2 to produce two second messengers:
Diacylglycerol (DAG) and Inositol tris-phosphate (IP3)
Plasma membrane Plasma
membrane
Cytoplasm
Nucleus
DAG
IP3
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Receptor-mediated activation of phospholipase C
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Phosphoinositide system
• second messengers produced are IP3, DAG and Ca2+
1. Gqα activates phospholipase C (PLC)
2. PLC cleaves PIP2 to IP3 and DAG
3. IP3 causes Ca2+ release from ER
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Phosphoinositide system4. DAG activates
membrane-bound protein kinase C
5. Protein kinase C phosphorylates substrate proteins
resulting in cellular responses
Protein kinase C requires DAG, Phospholipids and Ca2+ for maximal activity.