Introduction to Metabolism 2
By
Amr S. Moustafa, M.D.; Ph.D.
Assistant Prof. & Consultant, Medical Biochemistry Dept.
College of Medicine, [email protected]
Pathway Vs Chemical Reaction
Metabolic Pathway:
A multi-step sequence of chemical reactions
A product of first reaction becomes a substrate for second reaction
Integrated pathways: Metabolism
Metabolic Pathway: Glycolysis
Metabolic Map
Catabolism: Catabolic Pathways
ATP capturing of chemical energy
Anabolism: Anabolic Pathways
Precursor molecules into complex molecules
Endergonic reactions, require ATP
Divergent process
Catabolism Vs Anabolism
Regulation of Metabolism
Intracellular signals: (Rapid response)Substrate availabilityProduct inhibitionAllosteric activators
Intercellular communication:Direct contact (gap junction)Chemical signaling (hormones):
Second messengercAMP, cGMPCa/phosphatidylinositol
Transmission of Regulatory Signals
G-Protein Coupled Membrane Receptor
Signal Transduction
Actions of cAMP
AMP
1Phosphodiesterase
1
Signaling
• Signal transmission
• Signal amplification
• Tight regulation
• Cross-talksSynergism/antagonismDivergence/convergence
Signaling: G-Proteins
Trimeric proteins: α, β and γ
Types: Gs and Gi (αs and αi)
Active G-protein (α-GTP):
GTP replaces GDP
α-subunit dissociates from βγ
Inactivation of G-protein (αβγ-GDP) :
Inherent GTPase activity (α-subunit)
α, β and γ trimeric complex
Adenylyl Cyclase
Membrane-bound enzyme
ATP cAMP
Toxins and diseases:
Persistent stimulation by Vibrio cholerae
Persistant inhibition by Bordetella pertussis
cAMP-Dependent Protein Kinases
Activation:
cAMP bound to regulatory subunits
Release of catalytic subunits
Serine/threonine phosphorylation of proteins
Phosphorylated proteins:
Activated or inhibited enzymes
regulate ion channels
bind to DNA promoter: Induction/repression
Actions of cAMP
AMP
1Phosphodiesterase
1
Protein Kinases
Protein kinase A: cAMP-dependent
Protein kinase G: cGMP-dependent
Protein kinase C: Calcium/phospholipid-dependent
Signaling: Reversible Process
Dephosphorylation of proteins
Protein phosphatase
Inactivation of protein kinase
cAMP level
Inactivation of adenylyl cyclase
Phosphodiesterase
Inactivation of G-protein
Uncoupled hormone & receptor
Signaling: Regulation of Metabolism
First messenger: Hormone, e.g., glucagon
Hormone/receptor complex and G-proteins
Second messenger: cAMP
Cellular responses: Activation of cAMP-dependent protein kinase
Stimulation, e.g., glycogenolysis
Inhibition, e.g., glycogenesis
