Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431	Biochemistry	Fall 2008
Lecture Notes: 31 October	© R. Paselk 2008
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Introduction to Metabolism, cont.

Metabolic Pathways, cont.

Characteristics of pathways:

• Irreversible
• First committed step (flux generating step)
• Regulated
• Localized in eukaryotes
• Catabolic and anabolic pathways are generally distinguished by coenzymes and/or compartmentalization.

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:

• Stage I: Hydrolysis of polymers to monomeric units (fat fatty acids and glycerol, protein amino acids, etc.)
• Stage II: breakdown of products of Stage I to pyruvate, acetyl CoA, and/or intermediates of the Kreb's Cycle
• Stage III: Breakdown of Acetyl CoA by the Kreb's Cycle into carbon dioxide and water with the production of reducing equivalents (NADH etc.)
• Stage IV: Oxidation of the reducing equivalents by oxygen with the production of ATP via the Electron Transport System.

Organic Reactions in Metabolism

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

• Group-transfer reactions (transfer of an electrophile [acyl {RCOX}, phosphoryl {OPO₃X^2-}, and glycosyl groups] between nucleophiles [alcohols, amines, thiols, etc.])
• Redox Reactions
• Eliminations {eliminate H₂O, NH₃, ROH or RNH₂}, Isomerizations, Rearrangements
• C-C bond formation or breakage (condensation and cleavage reactions).

High Energy Compounds

Look at ATP. In the figure the bolded region (adenine base + ribose) 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. (text Figure 1-25)

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 G 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.

Pathway Diagrams

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Last modified 3 November 2008