Introduction to Metabolism 2 By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU

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 availability Product inhibition Allosteric activators Intercellular communication: Direct contact (gap junction) Chemical signaling (hormones): Second messenger cAMP, cGMP Ca/phosphatidylinositol

Transmission of Regulatory Signals

G-Protein Coupled Membrane Receptor

Signal Transduction

Actions of cAMP AMP 1 Phosphodiesterase 1

Signaling Signal transmission Signal amplification Tight regulation Cross-talks Synergism/antagonism Divergence/convergence

Signaling: G-Proteins Trimeric proteins: α, β and γ Types: G s and G i (α s and α i ) 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 1 Phosphodiesterase 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