Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 438

Introductory Biochemistry

Spring 2010

Lecture Notes: 24 March

© R. Paselk 2006
 
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Metabolic Pathways, cont.

Recall our definition from last time:

"[A] metabolic pathway is a series of enzyme-catalyzed reactions, initiated by a flux-generating step and ending with either the loss of products to the environment, to a stored product (a metabolic 'sink') or in a reaction that precedes another flux-generating step (that is, the beginning of the next pathway)." Where a flux generating step is a non-equilibrium reaction that generates the flux going through the pathway and to whose rate all other reactions of the pathway conform. Note that by this definition some pathways may be inter-organ while others may take place in single compartment. We will explore this definition/concept as we look at metabolism.

Characteristics of pathways:

The flux through a metabolic pathway is invariably controlled or regulated, most commonly by Feedback Inhibition, but also through Feed-forward activation. Regulation is one of the things that makes biochemistry "biological" and it will be a focus in our study.

The Stages of Catabolism [overhead]: For convenience we can breakdown catabolism into four hierarchical levels:

Organic Reactions in Metabolism

Organic Reaction Mechanisms: We can categorize all common biological reactions into four groups:

HIGH ENERGY COMPOUNDS

Look at ATP. In the figure the bolded region is the "recognition" part of the molecule, while the polyphosphate is the chemically active portion. Each of the phosphoric acid anhydride bonds is unstable. That is hydrolyzing either will release a lot of energy.

structural diagram of ATP

So why ATP? First, we want a compound with intermediate hydrolysis energy so it can pick up energy from some reactions and deliver to others. Second we want a kinetically stable molecule which is thermodynamically unstable. Thus acetic acid anhydride would not work: it is thermodynamically unstable to hydrolysis, but it is also kinetically unstable, with the carbonyl carbons wide open to water attack. Phosphoric acid anhydride is equally unstable, but is is sterically protected from water attack - in order to react quickly we need a catalyst - perfect.

ATP is sometimes referred to as a "Hi Energy" compound. High energy in this case does not refer to total energy in compound, rather just to energy of hydrolysis. Thus ATP is unstable to hydrolysis, or has a large negative deltaG for hydrolysis. For biochemistry High Energy is defined in terms of ATP: if a compound's free energy for hydrolysis is equal to or greater than ATP's then it is "High Energy," if its free energy of hydrolysis is less than ATP's then it is not a "hi energy" compound. Note that ATP has two hi energy anhydride bonds.

You should memorize the structures for ATP, ADP, & AMP.

Thermodynamics in Metabolism

Remember, the cool thing about thermo is that it is pathway independent - we can tell how much energy is available in an M&M by burning it in pure oxygen in a stainless steel container and tell you how far you can run on that M&M!

The tragedy of thermo, the other side of the coin, is that it tells nothing about the details - thermo gives us no idea about how the energy is used, or what steps are involved in its loss.

Remember also that for chemists and biologists the thermodynamic term generally of most interest is the Free Energy for a reaction, that is the energy available to do work.


Pathway Diagrams

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Last modified 24 March 2010