Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chem 431	Biochemistry	Fall 2001
Lecture Notes:: 26 October	© R. Paselk 2001
PREVIOUS		NEXT

THERMODYNAMICS IN METABOLISM, cont.

Recall that DG° ' = -RT lnK, DG° ' = -5700 log K (in joules). Thus free energy is related to the equilibrium constant, K. To provide a quantitative feeling for this relationship some values are tabulated below:

Similarly for non-equilibrium situations: DG° ' = -RT lnQ, where Q is the mass action expression, Q = ([C][D])/([A][B]) for A + B -> C + D. One advantage of using free energy is that it is easier to evaluate the overall equilibrium/energy for a series of sequential reactions (its additive instead of multiplicative): DG_tot = SDG. Often use to predict feasibility of pathways, possible energy yields, and to determine when individual reactions are not at equilibrium (important for determining potential control steps etc.).

Note that the overall free energy determines spontaneity of the reaction - the pathway doesn't matter! This is one of the cool things about thermodynamics, it is pathway independent. Thus can drive unfavorable reactions by linking with favorable reactions. This can be done:

1. Sequentially: , where the reaction of B to C pulls A to B; or
2. In parallel: , where the two reactions are linked

Example: glucose + phosphate to G-6-P (DG= +3300 cal) and ATP + water to ADP (DG= -7600 cal); mix together, no G-6-P (DG= -4300 cal). But link with enzyme, Glu + ATP = ADP + Pi (DG= -4300 cal). All of metabolism depends on such coupled reactions. In essence catabolic reactions drive anabolic reactions etc. via direct, and more commonly, indirect, multi-step, coupling.

Metabolism would be extremely complex if coupled processes directly, however. Instead use an intermediate energy carrier: ATP. Thus catabolic processes make ATP which can then be used for anabolic processes, locomotion, pumping ions across cell membranes (major contribution to basal metabolic rate or BMR), etc. Note that ATP is not used to store energy however. (Often compared to electricity's role in our culture).

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 "hi-energy." That is hydrolyzing either will release a lot of energy.

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.

HIGH ENERGY COMPOUNDS

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 DG 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.

GLYCOLYSIS

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. First let's look at Glycolysis to get an overview, then we will look at the reactions and enzymes of this pathway individually. We will then come back and look at the overall regulation and control of this pathway.

DIGESTION. But before we begin glycolysis let's take a brief look at how glucose gets to the tissue from food intake.

• 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 and release of glucose and fatty acids for use in the peripheral tissues.

GLYCOLYSIS 1

First if we look at the Glycolysis Pathway (overhead), we can break it into three phases:

• Phase 1: phosphorylation and rearrangement of glucose to give a molecule that can be cleaved to two inter convertible trioses: glucose to F-1,6-bis P (energy invested);
• Phase 2: oxidative phosphorylation of an aldehyde to give a mixed acid anhydride with subsequent transfer of the phosphate to ATP: DHAP & GA-3-P to 3-PGA (energy repaid);
• Phase 3: rearrangement of a phospho-ester to an enol-phosphate with subsequent transfer of phosphate to ATP: 3-PGA to Pyruvate (energy profit). The resulting pyruvate may now go on to the Kreb's TCA Cycle or be converted into lactate. In either case it is critical to regenerate the NAD⁺ or Glycolysis will come to a halt.

Pathway Diagrams

C431 Home

C431 Lecture Notes

Last modified 29 October 2001