Chapter 10 Introduction to Metabolism. Metabolism The sum of the chemical changes that convert nutrients into energy and the chemically complex products.

Chapter 10

Introduction to Metabolism

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

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

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

Metabolism

• Metabolism consists of catabolism and anabolism

• Catabolism: degradative pathways– Usually energy-yielding!

• Anabolism: biosynthetic pathways– energy-requiring!

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

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

Mutienzyme complex

Separateenzymes

Membrane Bound System

Organization of Pathways

Linear(product of rxns are substrates for subsequent

rxns)

Closed Loop(intermediates recycled)

Spiral(same set of

enzymes used repeatedly)

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

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

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

Enzyme Regulation of Flux

Metabolic Control Theory

• Pathway flux is regulated by multiple enzymes in a pathway.

• Control coefficient determined for each enzyme. = activity / 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

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

Metabolic Pathways are not at Equilibrium

• Metabolic pathways are not at equilibrium A <-> B• Instead pathways are at steady state.A -> B -> CThe 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.

Thermodynamics and Metabolism

• Standard free energy A + B <-> C + D

• Go’ =-RT ln[C][D]/[A][B]

• Go’ = -RT ln Keq

• Go’ < 0 (Keq>1.0) Spontaneous forward rxn

• Go’ = 0 (Keq=1.0) Equilibrium

• Go’ > 0 (Keq <1.0) Rxn requires input of energy

G (not Go’) is impt in vivo

• G = Go’ + 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.

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

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

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.

Phosphoryl-group Transfer