Download Mass-Action Ratios!

Mass-Action Ratios!
Metabolomics: study of intermediates and their movement
Mass-action ratios are the ratio of products over reactants for any given reaction
knowing whether this ratio is > or < the Keq (the ratio at
equilibrium) allows you to predict which way the reaction
will adjust (classic Le Chatelier's approach)
For instance
Glucose-6-P
Qphosphoglucomutase =
Glucose-1-P
Glycogen
phosphorylase
Glucose (shipped out)
Glucose-1-P
Glucose-6-P
phosphoglucomutase
UDP-Glucose pyrophosphatase
Glycogen synthase
Glycolysis
However, in biochemical processes, where reactions are often linked to other reactions, Le Chatelier's
Princple must take on a more global view. Looking at the ratio above, if Glu-6-P rises, bringing the ratio
above its "resting" or Keq state, equilibrium can be regained by shifting the reactions to the right
(glucose is shipped out, or glycolysis is continued). Similarly, if Glu-1-P builds up, it is too restrictive to
simply say the phosphoglucomutase reaction will shift right, when equilibrium can be reasserted by
shifting toward glycogen production (reaction on the left of Glu-1-P). To get a broader perspective about
how a series of reactions adjust, it is important to take a broader view of the mass action ratio idea.
Now consider any combination of related compounds (usually this is a chemical relationship, meaning
they share the same basic structure or are interconverted enzymatically, though possibly indirectly) and
think about what happens if that ratio is away from its natural "equilibrium" state.
Both of these reactions say something about the overall energy level of the cell;
when higher than a cell's average or "resting" state, it means that ATP or NADH is
probably available for synthetic reactions (remember that ATP and NADH are high
energy molecules, supplying energy for the cell's needs. When low, it tells the cell
that NADH or ATP is/are needed, and breakdown reactions are probably coming in
order to generate these high energy molecules (for instance, glycolysis).
Common ratios to consider
or AMP
or Pi, etc
NADH
ATP
or
NAD+
ADP
Notice that even with this broader ratio, high glucose can be adjusted by
increasing glycolysis OR by shipping the glucose out....likewise, high
pyruvate might encourage gluconeogenesis, or it might encourage
pyruvate to take another path to keep glycolysis going....
glucose as a measure of
Or how about pyruvate how the entire
glycolytic path
is working?
Ratios can be considered like a switch or pressure valve for a system - everything naturally returns to equilibrium by
releasing the "pressure" that concentration changes (causing ratios that are shifted from equilibrium) bring.
For instance, muscles have two methods for releasing pressure, allowing glycolysis to continue at a high
rate against the pressure of building up ATP, limiting NAD+ and possibly building up pyruvate ("anaerobic"):
Releasing the pressure of increasing pyruvate concentration and decreasing NAD+: Lactic acid production
O
O
NADH + H+
C
C
NAD+ O
O
CH3
O
C
H C OH
lactate dehydrogenase
pyruvate
CH3
lactate (lactic acid)
Because pyruvate is turned into lactate, it does not build up,
which would slow down the pyruvate kinase reaction (PEP -->
pyruvate). This would in turn slow down each of the enzymes in
the pathway, blocking the path or leading to other pressure
releases (branching pathways, like the pentose phosphate
pathway). Similarly, regenerating NAD+ allows the
glyceraldehyde-3-phosphate dehydrogenase reaction to continue
(and NADH/NAD+ to remain steady, rather than rising and
shutting off the sign that energy is still needed.
"Hiding" ATP, thereby keeping the ATP/ADP ratio lower than it really is, by phosphorylating creatine
C
C
CH2
ATP
H3C N
C NH2
NH2
creatine
O
O
O
O
creatine kinase
ADP
CH2
H3C N
O
O P
O
C NH2
NH
creatine phosphate
or phosphocreatine
Each cell has its own resting or average ATP/ADP ratio.
Muscles need to keep a reservoir of ATP, but an extremely
high ATP/ADP ratio would affect the equilibria of ALL
reactions that involve these nucleotides. By keeping a large
concentration of creatine, the high energy N-P bond can be
made using creatine kinase. When soluble ATP levels fall,
the reverse reaction spontaneously generates ATP by
cleaving the N-P bond. In this way, the ATP is "there," but
the ATP/ADP ratio is still low.
Nolta 2009