High Energy Compounds
Compiled by: Vivekananda Kedage., MSc

 

HIGH ENERGY COMPOUNDS< xml="true" ns="urn:schemas-microsoft-com:office:office" prefix="o" namespace="">

 

Certain compounds are encountered in the biological system which, on hydrolysis, yields energy. The term high-energy compounds or energy rich compounds are usually applied to substances which possess sufficient free energy to liberate at least 7 Cal/mol at pH 7.0. Certain other compounds which liberate less than 7 (table 1) Cal/mol (lower than ATP hydrolysis to ADP + Pi) are referred to as low- energy compounds.

 

Table 1 Standard free energy of hydrolysis of some important compounds

Compounds

∆Go (Cal/mol)

High – Energy Phosphates

 

Phosphoenol pyruvate

- 14.8

Carbamoyl phosphate

- 12.3

Cyclic AMP

- 12.0

1,3 – Bisphosphoglycerate

- 11.8

Phosphocreatine

- 10.3

Acetyl phosphate

- 10.3

S – Adenosylmethionine

- 10.0

Pyrophosphate

- 8.0

Acetyl CoA

- 7.7

ATP→ADP + Pi

- 7.3

Low energy compounds

 

ADP→AMP + Pi

- 6.6

Glucose 1-Phosphate

- 5.0

Fructose 6-Phosphate

- 3.8

Glucose 6-Phosphate

- 3.3

Glycerol 3-Phosphate

- 2.2

All the high energy compounds when hydrolyzed liberate more energy than that of ATP.Most of high energy compounds contain phosphate group (exception acetyl CoA) hence they are also called high energy phosphates.

 

Classification of high energy compounds

 There are at least 5 groups of high energy compounds (table 2)

Table 2 high energy compounds

Class

Bond

Example (s)

Pyrophosphates

– C – P – P

ATP, pyrophosphate

Acyl phosphates

   O  

  

– C – O ~ P

1,3- Bisphosphoglycerate, Carbamoyl phosphate, Acetyl phosphate.

Enol phosphates

– CH 

  

– C – O ~ P

Phosphoenol pyruvate

Thiol esters (thioesters)

   C 

  

– C – O ~ S –

Acetyl CoA, Acyl CoA

Guanido phosphates (phosphagens)

    |

– N~ P

Phosphocreatine, Phosphoarginine

 

High – energy bonds:  The high energy compounds possess Acid anhydride bonds (mostly phosphoanhydride bonds) which are formed by the condensation of two acidic groups or related compounds. These bonds are referred to as high energy bonds, since the free energy is liberated when these bonds are hydrolyzed. Lipmann suggested use of the symbol ~ to represent high energy bond. For instance, ATP is written as AMP ~ P ~ P.

 

ATP – the most important high energy compound

 

Adenosine triphosphate (ATP) is a unique and the most important high energy molecule in the living cells. The ATP molecule is a purine (adenine) nucleotide in which the adenine is attached in a glycosidic linkage to D – ribose. Three phosphoryl groups esterified to the 5 position of the ribose moiety in phosphoanhydride bonds. The two terminal phosphoryl groups (i.e., β and γ) are involved in the phosphoric acid anhydride bonding and are designated as energy rich or high energy bonds (fig 1 click link below).

http://hyperphysics.phy-astr.gsu.edu/hbase/biology/imgbio/atpmol.gif

 

The two terminal phosphoryl groups of ATP contain energy rich or high energy bonds. What this description is intended to convey is that the free energy of hydrolysis of an energy rich phosphoanhydride bond is much greater than would be obtained for a simple phosphate ester. High energy is not synonymous with stability of the bonding arrangement in question, nor does it refer to the energy required to break such bonds. The concept of high energy compounds implies that the products of the hydrolytic cleavage of energy rich bond are in more stable forms than the original compound. As a rule, simple phosphate esters (low energy compounds) exhibit negative ∆Go values of hydrolysis in the range 1 – 6 Cal/mol, whereas high energy bonds have negative ∆Go values in the range 7- 15 Cal/mol. Phosphate esters such as glucose 6 – phosphate and glycerol 3 phosphate are good examples of low energy compounds.

There are various reasons why certain compounds or bonding arrangements are energy rich. First, products of the hydrolysis of an energy rich bond may exist in more resonance forms than the precursor molecule. The more possible resonance forms in which a molecule can exist stabilize that molecule. The resonance forms for inorganic phosphate (Pi) can be written as indicated in fig 2. (a)

         O                        O-                           O-                                O-

                                  |                         |                          |

HO – P – O-   ↔ HO – P = O ↔ HO – P – O- ↔ HO+ = P – O-

          |                          |                                                 |

         O-                               O-                            O                               O-                    

 

 Fig 2:   a)  Resonance forms of phosphate

 

                                     O           O

                                               

                            HO – P – O – P – O-   

                                      |             |

                            O-             O-

 

 

                            b) Pyrophosphate

 

Fewer resonance forms can be written for ATP or pyrophosphate (PPi) fig 2 (b) than for phosphate (Pi).

Second, many high energy bonding arrangements have groups of similar electrostatic charges located in close proximity to each other in such compounds. Because like charges repel one another, hydrolysis of energy rich bonds alleviates this situation and, again, lends stability to the products of hydrolysis. Third, hydrolysis of certain energy rich bonds results in the formation of an unstable compound, which may isomerizes spontaneously to form a more stable compound. Hydrolysis of phosphoenolpyruvate is an example of this of compound. Fig 3

 

 

 

CH2      O                                 CH2                 O                 CH3

                      HOH                                                       | 

< xml="true" ns="urn:schemas-microsoft-com:vml" prefix="v" namespace="">C – O ~ P – O                                     C – OH + HO – P – O-    C = O

 |             |                                    |                         |                   |

COO-    O-                                 COO-                O-                COO-  

 

Phospho-   ∆Go = -14.8 Cal/mol  Enol -                (Spontaneous reaction) pyruvate-

Enol -                                            pyruvate                                                 (stable form)

Pyruvate               

Fig 3: Hydrolysis of Phosphoenolpyruvate

 

The ∆Go for isomerisation is considerable, and the final product, in this case pyruvate, is much more stable. Finally, if a product of the hydrolysis of a high energy bond is an undissociated acid, dissociation of the proton and its subsequent buffering may contribute to the overall ∆Go of the hydrolytic reaction. In general, any property or process that lends stability to products of hydrolysis tends to confer a high energy character to that compound.

ATP serves as the energy currency of the cell as is evident from the ATP – ADP cycle. As a result of its position midway down the list of standard free energies of hydrolysis (shown in red fig 1), ATP is able to act as donor of high energy phosphate to those compounds below it in the table. Likewise, provided the necessary enzymatic machinery is available, ADP can accept high energy phosphate to form ATP from those compounds above ATP in the table. The hydrolysis of ATP is associated with the large amount of energy.

 

                                ATP + H2O → ADP + Pi + - 7.3 < xml="true" ns="urn:schemas-microsoft-com:office:smarttags" prefix="st1" namespace="">< xml="true" ns="urn:schemas:contacts" prefix="st2" namespace="">Cal.

http://hyperphysics.phy-astr.gsu.edu/hbase/biology/imgbio/atptoadp.gif

 

The energy liberated is utilized for various processes like muscle contraction, active transport etc.  In effect, an ATP – ADP cycle connects these processes that generate ~P to those processes that utilize ~P (Fig 4). Thus, ATP is continuously consumed and regenerated. This occurs at a very rapid rate, since the total ATP/ADP pool is extremely small and sufficient to maintain an active tissue only for a few seconds. ATP acts as an energy link between Catabolism (degradation of molecules) and Anabolism (synthesis) in the biological system.

There are 3 major sources of ~P taking part in energy conservation or energy capture:

1)      Oxidative phosphorylation. This is the greatest quantitative source of ~P in aerobic organisms. The free energy to drive this process comes from respiratory chain oxidation within mitochondria.

2)      Glycolysis. A net formation of 2 ~P results from the formation of lactate from one molecule of glucose generated in 2 reactions catalyzed by phosphoglycerate kinase and pyruvate kinase, respectively.

3)      The citric acid cycle. One ~P is generated directly in the cycle at the succinyl thiokinase step.

Another group of compounds, Phosphagens, act as storage forms of high energy phosphate. These include Creatine phosphate, occurring in vertebrate muscle and brain, and Arginine phosphate, occurring in invertebrate muscle. Under physiologic conditions, phosphagens permit ATP concentrations to be maintained in muscle when ATP is rapidly being utilized as a source of energy for muscular contraction. On the other hand, when ATP is plentiful and the ATP/ADP ratio is high, their concentration can build up to act as a store of high energy phosphate (fig 5). In muscle, a Creatine phosphate shuttle has been described which transports high energy phosphate from mitochondria to the sarcolemma and which acts as a high energy phosphate buffer. In the myocardium, this buffer may be significance in affording immediate protection against the effects of infarction.

Fig 4: Role of ATP/ADP cycle in transfer of high energy phosphate  (click link below)

 

http://staff.jccc.net/pdecell/metabolism/atpcycle.gif

 

 

      P~ NH                                                                            H2N

             |                                  Creatine kinase                          |

            C = NH      ◄––––––––––––––––––––––––––►       C = NH

             |                                                                                 |

 H3C – N                        ADP                               ATP             N – CH3

             |                                                                                     |

            CH2 –COOH                                                                 CH2 – COOH

     Creatine phosphate          (∆Go = - 12.6 kJ/mol)                  Creatine

 

Fig 5: Transfer of high energy phosphate between ATP and Creatine

 

When ATP acts as a phosphate donor to form those compounds of lower free energy of hydrolysis (table 1), the phosphate group is invariably converted to one of low energy, e.g.

                                                         Glycerol kinase

Glycerol + Adenosine – P ~ P ~ P ––––––––––––––> Glycerol – P + Adenosine – P ~ P