introduction to metabolism 2 by amr s. moustafa, m.d.; ph.d. assistant prof. & consultant,...

Introduction to Metabolism 2

By

Amr S. Moustafa, M.D.; Ph.D.

Assistant Prof. & Consultant, Medical Biochemistry Dept.

College of Medicine, KSUamrsm@hotmail.com

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