Transcript Sample biochemistry presentation - STS

Unit II: Intermediary Metabolism
Chapter 8 (Lectures 8-11)
Basic Concepts of
Metabolism
AJG
Learning objectives: Introduction to metabolism
1 Introduction to metabolism
A. Define metabolism in terms of anabolic and catabolic processes
1. Compare, contrast, anabolic & catabolic pathways
2. Include the concept and the importance of electron carriers
3. Explain why catabolic pathways are considered convergent
4. Explain why anabolic pathways are considered divergent
B. Explain the importance of cell-cell communication in the regulation of
metabolism.
C. List the 4 different types of receptors and their basic mechanism of action
D. Give examples of the four types of receptors.
E. Describe the two second messenger systems( adenylate cyclase) and the
phophoinositide system
F. Indicate the receptors, G-protein and effector enzyme in each of these
systems.
G. Indicate what second messenger(s) are produced by activation of adenylate
cyclase and phospholipase C.
H. Indicate which protein kinase (PKA, PKC) is activated in both systems
Catabolism
• degradation
• convergent
• “oxidative”
• products:
ATP
FADH2
NADH
NADPH
Anabolism
•
•
•
•
synthesis
“reductive”
divergent
uses ATP
• products:
NAD+
FAD
ADP
NADP+
Stages of Catabolism
Stage 1
Stage 2
Stage 3
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
Intercellular signals
Extracellular signals are
converted to Intracellular
signals
OR
Signal Transduction
Intercellular signals
are
converted
to an
intracellular
signal in the
adjacent
cell
Intracellular signals
cAMP
Enzyme-P
Receptor-mediated Signal Transduction
(Extracellular signals)
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
Four general types of receptors
GPCR
1. Steroid receptor mechanism of signal transduction
1. Steroid receptor mechanism of signal transduction
mechanism may take hours or days (slow)
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
2. Gated ion channel
3. Receptor enzyme
(Catalytic receptor)
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
G-protein coupled receptor (GPRC)
produce intracellular 2nd messengers
4. GPCR and Intracellular Second Messengers
•
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. 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
second messenger systems
Stimulus: epinephrin/norepinephrine or glucagon
Receptors: β-adrenergic receptor or glucagon receptor
• Adenylate cyclase sytem:
• c-AMP(second messenger)
• Protein kinase A
Adenylate cyclase system
• second messenger
is cAMP
• cAMP activates
protein kinase A
• protein kinase A
phosphorylates
target proteins
• phosphodiesterase
hydrolyzes cAMP to
5’-AMP
G-protein coupled receptor (GPRC)
produce intracellular 2nd messengers
G-protein coupled receptor (GPCR)
produce intracellular 2nd messengers
• Phosphoinositide system:
• Inositol tris-phosphate
• Calcium
• Diacylglycerol
• Protein kinase C
P
P
Phosphatidylinositol 4, 5-bis-phosphate
Phosphatidylinositol 4, 5-bis-phosphate (PIP2)
Phosphatiylinositol-4,5-bis-phosphate (PIP2)
DAG
Phospholipase C
cleaves PIP2 to
generate IP3 and
DAG
IP3
Plasma
membrane
Plasma
membrane
DAG
Phospholipase C
(PLC) cleaves
PIP2 to produce
two second
messengers:
IP3
Cytoplasm
Diacylglycerol
(DAG) and
Inositol trisphosphate (IP3)
Nucleus
Receptor-mediated activation of phospholipase C
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
Phosphoinositide system
4. 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.