1. Introduction to Metabolism

2. Metabolism
The sum of the chemical changes that convert nutrients into energy and the chemically complex products of cells
Hundreds of enzyme reactions organized into discrete pathways
Substrates are transformed to products via many specific intermediates
Metabolic maps portray the reactions
Intermediary metabolism

3. A Common Set of Pathways
Organisms show a marked similarity in their major metabolic pathways
Evidence that all life descended from a common ancestral form
There is also significant diversity

4. The Sun is Energy for Life
Phototrophs use light to drive synthesis of organic molecules
Heterotrophs use these as building blocks
CO2, O2, and H2O are recycled

6. Metabolism Metabolism consists of catabolism and anabolism
Catabolism: degradative pathways
Usually energy-yielding!
Anabolism: biosynthetic pathways
energy-requiring!

8. Catabolism and Anabolism
Catabolic pathways converge to a few end products
Anabolic pathways diverge to synthesize many biomolecules
Some pathways serve both in catabolism and anabolism
Such pathways are amphibolic

10. Organization in Pathways
Pathways consist of sequential steps
The enzymes may be separate
Or may form a multienzyme complex
Or may be a membrane-bound system
New research indicates that multienzyme complexes are more common than once thought

11. Mutienzyme complex
Separate
enzymes
Membrane
Bound System

12. Organization of Pathways
Closed Loop
(intermediates recycled)
Linear
(product of rxns are substrates for subsequent rxns)
Spiral
(same set of enzymes used repeatedly)

13. Metabolism Proceeds in Discrete Steps
Enzyme specificity defines biosynthetic route
Controls energy input and output
Allow for the establishment of control points.
Allows for interaction between pathways

14. Regulation of Metabolic Pathways
Pathways are regulated to allow the organism to respond to changing conditions.
Most regulatory response occur in millisecond time frames.
Most metabolic pathways are irreversible under physiological conditions.
Regulation ensures unidirectional nature of pathways.
Flow of material thru a pathway is referred to as flux.
Flux is regulated by supply of substrates, removal of products, and activity of enzymes

15. Enzyme Regulation of Flux
Common mechanisms
feedback inhibition – product of pathway down regulates activity of early step in pathway
Feedforward activation – metabolite produced early in pathway activates down stream enzyme

16. Metabolic Control Theory
Pathway flux is regulated by multiple enzymes in a pathway.
Control coefficient determined for each enzyme. = D activity / D enzyme concentration.
Enzymes with large control coefficients impt to overall regulation.
Recent finding suggest that the control of most pathways is shared by multiple pathwayt enzymes

17. Regulating Related Catabolic and Anabolic Pathways
Anabolic & catabolic pathways involving the same compounds are not the same
Some steps may be common to both
Others must be different - to ensure that each pathway is spontaneous
This also allows regulation mechanisms to turn one pathway and the other off

20. Metabolic Pathways are not at Equilibrium
Instead pathways are at steady state.
A -> B -> C
The rate of formation of B = rate of utilization of B.
Maintains concentration of B at constant level.
All pathway intermediates are in steady state.
Concentration of intermediates remains constant even as flux changes.

21. Thermodynamics and Metabolism
Standard free energy A + B <-> C + D
DGo’ =-RT ln[C][D]/[A][B]
DGo’ = -RT ln Keq
DGo’ < 0 (Keq>1.0) Spontaneous forward rxn
DGo’ = 0 (Keq=1.0) Equilibrium
DGo’ > 0 (Keq <1.0) Rxn requires input of energy

22. DG (not DGo’) is impt in vivo
DG = DGo’ + RT ln Q
Q (mass action ratio) = [C]’[D]’/[A]’[B]’
Actual [reactants] and [products] used to determine Q.
Because reactions are at steady state not equilibrium, Q does not equal Keq
When Q is close in value to Keq = near-equilibrium rxn (reversible)
If Q is far from Keq = metabolically irreversible rxn.

23. ATP ATP is the energy currency of cells
In phototrophs, light energy is transformed into the light energy of ATP
In heterotrophs, catabolism produces ATP, which drives activities of cells
ATP cycle carries energy from photosynthesis or catabolism to the energy-requiring processes of cells

24. Phosphoric Acid Anhydrides
ADP and ATP are examples of phosphoric acid anhydrides
Large negative free energy change on hydrolysis is due to:
electrostatic repulsion
stabilization of products by ionization and resonance
entropy factors

26. Phosphoryl-group Transfer
Energy produced from a rxn can be coupled to another rxn that requires energy to proceed.
Transfer of a phosphate group from high energy phosphorylated compounds can activate a substrate or intermediate of an energy requiring rxn.
A-P + ADP -> A + ATP, ATP +C-> ADP + C-P
The ability of a phosphorylated compound to transfer a phosphoryl group is termed its phosphoryl-group-transfer-potential.

27. Phosphoryl-group Transfer