Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431	Biochemistry	Fall 2001
Lecture Notes:: 24 October	© R. Paselk 2001
PREVIOUS		NEXT

INTRODUCTION TO METABOLISM

Catabolism: degradation of molecules to provide energy.

Anabolism: reactions using energy to synthesize new molecules for growth etc.

Metabolic Pathways: (overhead - Interactions of Metabolic Pathways) sequences of consecutive enzyme catalysed reactions which are readily studied and traced. A more rational definition is that of Newsholme and Leach (Biochemistry for the Medical Sciences, Wiley, 1983: pg.42) "[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:

• 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 we will focus on it 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. These stages are summarized in G&G's Figure 18.6 on p575.

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).

THERMODYNAMICS IN METABOLISM

Remember that the Free Energy for a reaction, that is the energy available to do work, is defined as: DG = G_products- G_reactants = DH - T DS. And that when the free energy is negative we say the reaction is spontaneous, which simply means the reactants are favored in the reaction equation as written. Note when a reaction is at equilibrium then the DG is zero. Since free energy depends on conditions, chemists tabulate free energies under Standard Conditions, (DG°): 298 K, 1 atm., with all concentrations at 1 M. For biological systems we define a slightly different standard free energy with [H⁺]= 10^-7 M (pH=7), DG° '.

For non-standard conditions can find the free energy using: DG = DG° ' + RT lnQ, but for equilibrium the free energy is zero, so DG° ' = -RT lnK, DG° ' = -5700 log K (in joules). Thus free energy is related to the equilibrium constant, K.

Pathway Diagrams

C431 Home

C431 Lecture Notes

Last modified 24 October 2001