CHAPTER 15Metabolism: Basic

Conceptsand Design

Chapter 15 – An overview of Metabolism

Metabolism is the sum of cellular reactions

- Metabolism – the entire network of chemical reactionscarried out by living cells

- Metabolites – small molecule intermediates in degradationand synthesis of polymers

- Catabolic reactions – degrade molecules to create smaller molecules – produces energy

- Anabolic reactions – synthesize molecules for cell maintenance,growth and reproduction – requires energy.

Figure 15.1-glucose metabolism

The eventual fate of glucose is toconvert it to CO2 and H2O w/the generation of ATP.

The aerobic fate of pyruvateis to produce 3 CO2 molecules

Figure 15.2: Many metabolic pathways are linked together

Key to all catabolic and anabolic reactions is that energeticallyunfavorable reactions can be driven by favorable reactions.

Enzymes are good at coupling reactions when needed:

A B + C Go' = +21 kJ/mol

B D Go' = -34 kJ/mol

A D + C Go' = -13 kJ/mol

unfavorable

favorable

favorable

The coupled reaction is favorable.

The Free Energy of ATP

- Energy from oxidation of metabolic fuels is largely recoveredrecovered in the form of ATP

Glucose + O2 CO2 + H2O and electron transport togethermakes ~ 32 ATPs per cycle

ATP contains 2 phosphoanhydride

bonds

ATP is an “energy-rich” compound It has lots of “stored energy”

- A large amount of energy is released in the hydrolysis ofthe phosphoanhydride bonds of ATP (and GTP, UTP, CTP)

- All nucleoside phosphates have nearly equal standard freeenergies (DG’s) of hydrolysis.

Why does ATP have so much stored energy??

1. Electrostatic repulsion among negatively charged oxygens of phosphoanhydrides of ATP

2. Solvation of products (ADP and Pi) or AMP and PPi)are better solvated by water than that of ATP

3. Resonance Stabilization of Pi- Phosphates are particularly stable

Free energy (-45.6 kJ/mol) that can be coupled

to unfavorable reactions

Free energy (-30.5 kJ/mol) that can be coupled

to unfavorable reactions

The hydrolysis of ATP

H2O

+

Pi

H2O+ PPi

(pyrophosphate)

Figure 15.6- ATP is centrally located in the phosphoryl-transferreactions

Notice the 1,3-BPG and PEP are more negative in DGo’these two will essentially drive the production of ATP in glycolysis.

Excellent forQuick bursts of energy Clinical Insights

Figure 15.9 The ATP-ADP Cycle

The oxidation ofcarbon fuels to generate reducedcofactors

The oxidation of carbon fuels is linked with reduction

Reduced Coenzymes Conserve Energyfrom Biological Oxidation

- Amino acids, monosaccharides and lipids are oxidized in the catabolic pathways

- Oxidizing agents – accept electrons and is reduced

- Reducing agents – lose electrons and is oxidized

- Oxidation of one molecule must be coupled with the reductionof another molecule

Ared + Box Aox + Bred

Fuels that are highly reduced can be oxidized for energy

Highlyreducedcarbon

HighlyoxidizedcarbonElectrons must be transferred

but to what?????

vs

More reduced

Compound with high energetic phosphoryl groups attachedcan couple with carbon oxidation and electron transfer

Other reactions are coupled to this oxidation reaction.

However this reaction does not occur in one step as shown.

Electrons are transferred to a oxidizing agent (NAD+)

Oxidized

Reduced

High energy 1,3-BPG can be used to drive the formation of ATP

Very high energyphosphoryl compound

The electron carrierNicotinamide adenine dinucleotide (NAD+)

Figure 15.12

Transfer ofa hydride (H-)

Common redox reaction

The electron carrierFlavin adenine dinucleotide (FAD)

Figure 15.13

Figure 15.16: the carriers of two carbon units (acetyl groups)Coenzyme A(CoA)

Coenzymes are derived from most vitamin supplements

Figure 15.19: Energy Charge Regulates Metabolism

Energy Charge = All ATPAll AMP

EC range is usually 0.80 to 0.95.

EC range is usually 0.80 to 0.95.

Metabolic Pathways are Regulated- Biosythesis and degradation pathways have reactions in common.

- Metabolism is highly regulated to permit organismsto respond to changing conditions

- Most pathways contain one or more steps that are irreversible

- These regulated, irreversible reactions are always distinct from within different pathways.

- Flux – flow of material through a metabolic pathwayFlux depends upon:

- Supply of substrates- Removal of products- Properties of enzymes

Regulated pathway through a Allosteric Inhibition

Flux through the pathway is regulated depending on the concentration of P

- Product of a pathway controls the rate of its own synthesisby inhibiting an early step (usually the first “committed”step (unique to the pathway).

- Metabolite early in the pathway activates an enzyme furtherdown the pathway

B is an allosteric activator

Regulated pathway through a Allosteric Activation

- Interconvertible enzymes can be rapidly and reversiblyaltered by covalent modification.

- The addition/removal of phosphoryl groups is one example

Kinases vs. Phosphatases

Assignment

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