# Why energy of some intermediates of glycolysis increases?

It is possible that I do not understand the concept of energy, but according to the diagram in my book, the energy between steps 4 and 5 and between 6 and 8 increases. How is this possible? Also, as ATP is invested in steps 1 and 3, shouldn't the energy increase there?

Step 1:

Phosphorylation activates glucose for the following reactions in the pathway. However, the formation of such a phosphoester is thermodynamically unfavourable and requires energy input to operate in the forward direction. The energy comes from ATP, a requirement that at first seems counterproductive.

$$\ce{-D-Glucose + ATP^4- → -D-glucose-6-phosphate^2- + ADP3 H+}$$
$\Delta G$ = -16.7 kJ/mol

and energy is released.

Step 3:

Once again, the substrate that provides the phosphoryl group is ATP. Like the hexokinase/ glucokinase reaction, the phosphorylation of fructose-6-phosphate is a priming reaction and is endergonic(energy absorbed):

Fructose-6-P + Pi +fructose-1,6-bisphosphate $\Delta G$ = 16.3 kJ/mol

When coupled (by phosphofructokinase) with the hydrolysis of ATP, the overall reaction becomes exergonic:

Fructose-6-P + ATP → fructose-1,6-bisphosphate + ADP

$\Delta G$ = -14.2 kJ/mol

Step 4:

Fructose bisphosphate aldolase cleaves fructose-1,6-bisphosphate between the C-3 and C-4 carbons to yield two triose phosphates. The products are dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate. The reaction has an equilibrium constant of approximately 10^-4 M, and a corresponding $\Delta G$ of +23.9 kJ/mol.

(the equilibrium is thus greatly influenced by concentration.)

Step 6:

In the first glycolytic reaction to involve oxidation–reduction, glyceraldehyde-3- phosphate is oxidized to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase.

Although the oxidation of an aldehyde to a carboxylic acid is a highly exergonic reaction, the overall reaction involves both formation of a carboxylic– phosphoric anhydride and the reduction of NAD to NADH and is therefore slightly endergonic at standard state, with a $\Delta G$ of + 6.30 kJ/mol.

(The free energy that might otherwise be released as heat in this reaction is directed into the formation of a high-energy phosphate compound, 1,3-bisphosphoglycerate, and the reduction of NAD.)

Step 7:

Here the glycolytic pathway breaks even in terms of ATPs consumed and produced with this reaction.The enzyme phosphoglycerate kinase transfers a phosphoryl group from 1,3-bisphosphoglycerate to ADP to form an ATP.

The phosphoglycerate kinase reaction is sufficiently exergonic at standard state to pull the G-3-P dehydrogenase reaction along. (In fact, the aldolase and triose phosphate isomerase are also pulled forward by phosphoglycerate kinase.) The net result of these coupled reactions is

Glyceraldehyde-3-phosphate + ADP + Pi + NAD → 3-phosphoglycerate + ATP + NADH + H+ $\Delta G$ = -12.6 kJ/mol

(Important: Another reflection of the coupling between these reactions lies in their values of $\Delta G$ under cellular conditions, despite its strongly negative the phosphoglycerate kinase reaction operates at equilibrium in the erythrocyte ($\Delta G$ =0.1 kJ/mol).

So in this case you'ill notice factors that influence energy expenditure and gain. Step 1 and 3 (exegonic reactions have net -G hence ) will see energy being released (and accroding to your diagram there is a decrease. Conversely in Step in steps 4-5 (reaction not favoured but due to concentration proceeds and is aided by energy and 6-7( energy is absorbed to form a high energy compound 1,3-bisphosphoglycerate) and 7-8 is mainly determined by reaction environment and relative concentrations of substrates and is slightly endergonic in above case.

Hope this helps

Reference

Biochemistry 4th Ed (Grisham)

The steps in question are under equilibrium. You can access all of them quickly, but the system will eventually find the low energy pyruvate at the end of the reaction. By Le Châtelier's principle, as you make more pyruvate and deplete the intermediate immediately before it, the system will be able to readjust and continually move towards making more pyruvate.