1. Basic Concepts of Metabolism
Unit II: Intermediary Metabolism
Chapter 8 (Lectures 8-11)
Basic Concepts of Metabolism
AJG

2. Learning objectives: 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

5. Catabolism degradation convergent “oxidative” products: ATP FADH2 NADH
NADPH

6. Anabolism synthesis “reductive” divergent uses ATP products: NAD+ FAD
ADP
NADP+

7. Stages of Catabolism

8. Stage 1
Stage 2
Stage 3

9. 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

10. Intercellular signals

12. Extracellular signals are converted to Intracellular signalsOR
Signal Transduction

13. are converted to an intracellular signal in the adjacent cell
Intercellular signals
are converted to an intracellular signal in the adjacent cell
Intracellular signals
cAMP
Enzyme-P

14. Receptor-mediated Signal Transduction (Extracellular signals)
4 basic types of signal transduction
pathways:
Steroid receptor
Gated ion channel
Receptor enzyme (Catalytic receptor)
G-protein coupled receptor (GPCR) produce intracellular 2nd messengers

15. Four general types of receptors
GPCR

16. 1. Steroid receptor mechanism of signal transduction

17. 1. Steroid receptor mechanism of signal transduction
mechanism may take hours or days (slow)

18. 2. Gated ion channel receptor linked to ligand or voltage-gated ion
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

19. 2. Gated ion channel

20. Receptor enzyme
(Catalytic receptor)

21. 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

22. G-protein coupled receptor (GPRC) produce intracellular 2nd messengers

23. 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:
Adenylate cyclase system (cAMP)
Calcium/phosphatidylinositol system (IP3, DAG, Ca2+)

24. 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

25. Adenylate cyclase sytem:
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

27. Adenylate cyclase system
second messenger is cAMP
cAMP activates protein kinase A
protein kinase A phosphorylates target proteins
phosphodiesterase hydrolyzes cAMP to 5’-AMP

29. G-protein coupled receptor (GPRC) produce intracellular 2nd messengers

30. Phosphoinositide system:
G-protein coupled receptor (GPCR) produce intracellular 2nd messengers
Phosphoinositide system:
Inositol tris-phosphate
Calcium
Diacylglycerol
Protein kinase C

31. Phosphatidylinositol 4, 5-bis-phosphate

32. Phosphatidylinositol 4, 5-bis-phosphate (PIP2)

33. Phosphatiylinositol-4,5-bis-phosphate (PIP2)
DAG
Phospholipase C cleaves PIP2 to generate IP3 and DAG
IP3

34. Cytoplasm Plasma membrane Plasma membrane Nucleus
DAG
Phospholipase C (PLC) cleaves PIP2 to produce two second messengers:
Diacylglycerol (DAG) and Inositol tris-phosphate (IP3)
IP3
Cytoplasm
Nucleus

35. Receptor-mediated activation of phospholipase C

36. 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

37. 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.