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
Read Chapter 15Read Chapter 16
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