Chem 438 - Introductory Biochemistry - Spring 2013

Lecture Notes:

Introduction to Metabolism, cont.

The Stages of Catabolism [Slide]: 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 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. [Figure 10.12]

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.[Table10.4]

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

Carbohydrate Metabolism

Glycolysis is going to be our first pathway, and it is arguably the most important and universal of the metabolic pathways. Thus we will spend extra time on it, exploring it in some detail from a variety of perspectives. But before we begin glycolysis let's take a brief look at how glucose (and carbohydrate generally) gets to the tissue from food intake.

DIGESTION.

Initial, limited, breakdown of starch in mouth by salivary amylase
Low pH of stomach inactivates salivary amylase, denatures many proteins etc.
In duodenum digestive enzymes are added from the pancreas (pancreatic amylase, lipases, proteases), pH is neutralized, and detergents (bile acids) are added from gall bladder.
Starches, Proteins, Lipids are all hydrolyzed in duodenum and small intestine where monomers are absorbed across intestinal epithelium. Amino acids and sugars are released into the portal vein to travel to the liver and then the rest of the body.
First pass through the liver removes sugars and most of the amino acids for processing, storage with the release of glucose and fatty acids over time for use in the peripheral tissues.

Pathway Diagrams

C438 Home

Lecture Notes

Last modified 11 March 2013

Humboldt State University ® Department of Chemistry

Richard A. Paselk