Reactions/Energies of Glycolysis
Reactions/Energies of Glycolysis
There are ten steps to glycolysis. Most instructors require students to memorize the molecular structures and enzyme names for each reaction of glycolysis, because it is such a universally important pathway. You should clarify this with your instructor. The Quizzing section is a convenient way to learn these things.
Highlights of the reactions:
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Enzyme: Hexokinase |
Notes
- ATP energy is used. Hexokinase is capable of phosphorylating
other 6-carbon sugars similarly, such as galactose, fructose,
and mannose.  is negative, so it favors making
glucose-6-phosphate (G6P), but the product of the reaction (G6P)
can reach high enough concentration to inihibit hexokinase and
limit glycolysis. |
= -16.7 kJ/mol |
| Reaction Picture |
| Enzyme: Phosphoglucoisomerase | |
| This is an aldose-ketose isomerization
that proceeds through an enediol intermediate. G6P is the aldose
and fructose-6-phosphate (F6) is the ketose. Phosphoglucoisomerase,
which catalyzes this isomerization, must not be confused with
phosphoglucomutase, the enzyme that interconverts G6P and glucose-1-phosphate
(G1P). The for the isomerization of G6P to
F6P is only slightly positive, so it strongly favors neither
reactants nor products in this reaction. |
|
|
D-fructose-6-phosphate + ATP <=> D-fructose-1,6-bisphosphate |
Enzyme: Phosphofructokinase |
| ATP energy is used to phosphorylate
F6P to fructose-1,6-bisphosphate (F1,6BP). This reaction is the
key to understanding how regulation of glycolysis is regulated.
The enzyme, phosphofructokinase (PFK), is allosterically regulated
by AMP (on), ADP (on), ATP (off), citrate (off), and fructose-2,6-bisphosphate
(F2,6BP) (on). The most potent of these is F2,6BP. The of -14.2 kJ/mol favors formation of F1,6BP fairly
strongly. Consequently, the reaction is essentially irreversible
in vivo. At this point all of the energy inputs for glycolysis
are complete. |
|
| D-fructose-1,6-bisphosphate <=> Dihydroxyacetone phosphate + D-Glyceraldehyde-3-Phosphate | Enzyme: Fructose-1,6-Bisphosphate Aldolase |
| In this reaction, F1,6BP is cleaved
to yield two three-carbon intermediates, glyceraldehyde-3-phosphate
(G3P and dihydroxyacetone phosphate (DHAP). The large positive
(+23.9 kJ/mol) strongly favors the reverse reaction
under conditions where reactants and products are present in
relatively equal quantitities. In muscle, however, the concentrations
of G3P and DHAP are kept low enough that the forward reaction
is favored overall . This is a good example of how a reaction
that is unfavorable at standard state conditions can be made
favorable in the cell by removing products as they are formed. |
|
| Enzyme: Triose Phosphate Isomerase | |
|
Notes - The
isomerization of DHAP to G3P, like the isomerization of G6P to
F6P (reaction 2 above), proceeds through an enediol intermediate.
Additionally, the isomerization of DHAP also has a positive For all reactions that follow in this section, keep in mind that the six-carbon glucose has been split into two three-carbon units. Thus, to account for everything properly, remember that there are two of each three carbon compound in the reactions shown. |
|
| D-Glyceraldehyde-3-Phosphate + NAD+ + Pi <=> 1,3 bisphosphoglycerate + NADH + H+ | Enzyme: Glyceradehyde-3-Phosphate Dehydrogenase |
| Notes - In
this reaction, G3P is phosphorylated and oxidized, so something
(NAD+) must be concomitantly
reduced. As a result, the NAD+/NADH
balance in the cell is important. If the concentration of NAD+ is low, the reverse reaction is favored, preventing
glycolysis from occurring aerobically. Instead it must occur
anaerobically. Thus this reaction determines whether glycolysis
occurs aerobically or anaerobically. 1,3-bisphosphoglycerate
(1,3BPG), the reaction product, contains an acylphosphate group,
which has a standard free energy of hydrolysis of 49.4kJ/mol.
Thus, 1,3BPG is capable of synthesizing ATP via a substrate-level
phosphorylation. The slightly positive shows that
the reverse reaction is slightly favored at standard conditions.
In the cell, however, the forward reaction is favored, thanks
partly to the high NAD+/NADH
ratio normally present. Note also that the NADH produced in this
reaction can be used to make three molecules of ATP in aerobic
glycolysis (when oxidative phosphorylation is occurring). Finally,
glyceraldehyde-3-phosphate dehydrogenase uses a thiol group in
catalysis, which can be inhibited by iodoacetate and heavy metals,
such as mercury. |
|
| Enzyme: Phosphoglycerate Kinase | |
| Notes - This reaction is a substrate-level phosphorylation of ADP to produce 3-phosphoglycerate (3PG) and the first ATP of glycolysis. Because two molecules of ATP are produced per molecule of glucose, the net yield of ATP is zero at this stage of glycolysis. | = -18.8 kJ/mol |
| Enzyme: Phosphoglycerate Mutase | |
| Notes - The for the isomerization slightly favors
formation of 3PG over 2PG under standard conditions, but in the
cell the concentration of 3PG is kept high relative to the concentration
of 2PG, which drives the reaction to the right. |
|
|
2-phosphoglycerate <=> Phosphoenolpyruvate + H2O |
Enzyme: Enolase |
Notes - This
reaction is a simple dehydration (or   elimination)
of 2PG to form phosphoenolpyruvate (PEP), but it has the effect
of increasing the energy of hydrolysis of the phosphate bond
almost four fold (from -15.6 kJ/mol in 2PG to -61.9 kJ/mol in
PEP). This high free energy of hydrolysis is necessary for the
next step in glycolysis, which is another substrate level phosphorylation
of ADP to form ATP. |
|
|
Phosphoenolpyruvate + ADP + H+ <=> Pyruvate + ATP |
Enzyme: Pyruvate Kinase |
| Notes - This
reaction is important for several reasons. First, it generates
ATP from the substrate-level phosporylation of ADP, putting the
balance for glycolysis at a net gain of two molecules of ATP
per molecule of glucose. Second, it is very favorable energetically,
serving to "pull" the two preceding reactions (both
of which have slightly positive values) forward.
Third, the enzyme catalyzing the reaction, pyruvate kinase, is
allosterically inactivated by ATP, alanine, and acetyl-CoA, allosterically
activated by F1,6BP, and is inactivated by covalent modification
(phosphorylation) from the kinase cascade. |
|
See also: Gluconeogenesis
and Glycolysis Interregulation Link Page,
Alanine, Acetyl-CoA,
Fructose-2,6-Bisphosphate, AMP, Oxidative Phosphorylation
(from Chapter 15)
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