Definition of ATP
The energy-storing organic complex known as the ATP molecule (adenosine triphosphate) powers a wide range of intracellular biological processes. In animals, the breakdown of consumed carbohydrate molecules produces some chemical energy, which is then stored in the chemical bonds as ATP. Whereas plants use photosynthesis to convert light energy into ATP, which is then used as an energy source for growth and cellular activities.
This ATP then releases energy as fuel to power cellular functions like muscle contraction, nerve impulse transmission, and biomolecule synthesis (including the production of proteins, DNA, RNA, amino acids, lipids, and vitamins), among others.
The fact that ATP fuels additional ATP synthesis during the breakdown of chemical compounds during glycolysis. Various catalytic enzymes use cellular ATP as their energy source to perform metabolic processes. As a result, ATP is frequently described as the “molecular unit of currency” of intracellular energy transfer.
The majority of ATP molecules are produced in a cellular organelle, mitochondria, by oxidative phosphorylation. However, uncoupling proteins found on the inner membrane of mitochondria will decrease the amount of ATP produced.
Structure of ATP
Adenine, a purine base, is joined to the first carbon atom of a pentose sugar (ribose) to form the nucleotide known as ATP (adenosine triphosphate).
While the fifth carbon atom of the ribose sugar is attached to three phosphate groups by a glycosidic bond. These three phosphates are attached by two phosphodiester bonds, which are esterified higher energy bonds.
Energy is produced by the hydrolysis of the phosphoanhydride bond between the second and third phosphate groups of the ATP molecule. ADP, a molecule with two phosphate groups, is created when the third phosphate molecule is eliminated.
The removal of a second phosphate from ADP to create AMP (adenosine monophosphate), on the other hand, will also result in the release of energy.
In order to create favorable reactions in a cell, the free energy that has been released will be transferred to additional molecules. By forming a fresh phosphoanhydride bond, AMP can then be converted back into ADP or ATP and store energy once more.
As they participate in biological processes, AMP, ADP, and ATP are constantly interconverted in the cell. Therefore, regenerating ATP from AMP and ADP is necessary to maintain a healthy level of energy in the body.
This procedure enables ATP to store energy like a rechargeable battery for later use.
Intracellular ATP Function
- The well-known energy-storing molecule adenosine triphosphate (ATP) can drive and take part in a number of intracellular processes.
- An enzyme called ATP kinase uses intracellular ATP as an energy and phosphate source to phosphorylate and activate biomolecules.
- Cyclic AMP, a second messenger in the signal transduction pathway, is created by the enzyme adenylyl cyclase using ATP.
- ATP can be incorporated into nucleic acids, such as DNA and RNA, by the polymerases in the processes of replication and transcription, respectively.
- By using one method to obtain energy and another to contribute to cellular energy charge to biological reactions, ATP maintains cellular homeostasis and contributes to overall energy balance.
- Intracellular homeostasis during exercise depends on adenosine triphosphate (ATP) availability and ATP demand being in balance.
- Additionally, intracellular ATP has the ability to function as a signaling molecule for opening the potassium channel, which increases heart rate.
Extracellular ATP Function
- For certain purinergic receptors, ATP also functions as an extracellular signaling molecule to promote a wide range of signaling processes, such as apoptosis, neurotransmission, inflammation, and bone remodeling (or bone metabolism).
- Inflammasomes can be activated by ATP, which can inhibit the growth of cancer cells.
- Adenosine signaling can prevent lipopolysaccharide-stimulated macrophages from producing several proinflammatory cytokines (TNF-, IL-6, and IL-8), while also causing them to release the anti-inflammatory cytokine IL-10.
- It has also been demonstrated that nearly every cell type in human skin is affected in a variety of ways by extracellular ATP and its metabolite, adenosine.
- The skin’s inflammatory, regenerative, and fibrotic reactions to a mechanical injury can all be directly influenced by ATP.
- The proliferation of melanocytes and the progression of apoptosis have both been shown to be indirectly influenced by ATP.
- Additionally, ATP demonstrates a complex role in Langerhans cell-directed adaptive immunity. Additional research into extracellular ATP’s effects on human skin could result in the creation of brand-new treatments for skin damage, inflammation, and a variety of other cutaneous conditions.
- Particularly through its metabolite, adenosine, ATP functions as an immunosuppressive molecule.
- According to research, the ectonucleotidases CD39 and CD73 inhibit the actions of innate and adaptive immune cells by converting extracellular adenosine triphosphate (ATP) to adenosine.
- Extracellular ATP can stimulate blood cells to proliferate or differentiate, chemotactically move in one direction or another, release cytokines or lysosomal components, or produce reactive oxygen or nitrogen species.
- In macrophages derived from monocytes, extracellular ATP promotes accelerated cell autophagy. The usefulness of metabolites in informing the metabolic supply pathways of the magnitude of ATP demand.
What are the functions of ATP-derived compounds, ADP, AMP, cAMP inside the cell?
Adenosine monophosphate (AMP), adenosine diphosphate (ADP), and cyclic AMP (cAMP) are ATP-derived substances made in the cell by various mechanisms. They play a specific role inside the cell after production, though.
1. ADP Function
Another name for adenosine diphosphate (ADP) is adenosine pyrophosphate (APP). ADP is involved in a number of biological processes, including the repair of cell damage and the regulation of which genes are “turned on” to produce proteins. ADP, for instance, can trigger a number of different mechanisms when it is present as Poly (ADP-ribose).
The breaks in the DNA strand activate the enzyme Poly (ADP-ribose) polymerase, which catalyzes the sequential transfer of ADP-ribose units from NAD to nuclear proteins (present on the chromosomes).
The resulting poly (ADP-ribose) units unwind the tightly packed nucleosomal structure of isolated chromatin; thus inducing the DNA repair mechanism (6).
Recent findings also stated that the presence of poly (ADP-ribose) can increase the DNA ligase activity; this may enhance the cell capacity for successful completion of DNA repair. Basically, ADP will be generated from ATP by losing a terminal phosphate group, and this process releases energy.
By gaining one phosphate group, AMP can also be converted into ADP, a process that consumes energy.
Cells get the energy they need to carry out their daily activities from the conversions that take place between AMP, ADP, and ATP during cellular respiration.
2. AMP Function
The fifth carbon atom of the ribose sugar is where adenosine monophosphate (AMP), also known as 5′-adenylic acid, is attached. This molecule, which contains adenine, one of the genetic code’s building blocks, has been discovered in ribonucleic acid (RNA).
AMP functions as a messenger molecule for the synthesis of proteins in the form of RNA. ATP in other forms, like tRNA and rRNA, acts as translation machinery.
Two different processes will result in the production of AMP. First, the enzyme adenylate kinase will change two ADP molecules into one ATP molecule and one AMP molecule.
Second, AMP is produced when one high-energy phosphodiester bond within ADP is hydrolyzed.
Third, one molecule of AMP is produced and incorporated into the lengthening nucleotide chain as a result of the hydrolysis of two phosphodiester bonds of ATP during DNA or RNA polymerization by the polymerase.
The breakdown of RNA also results in its production. It can later be transformed into uric acid, which is excreted through the bladder and is a component of urine.
3. cAMP Function
The intracellular second messenger, cyclic adenosine monophosphate (cAMP), participates in numerous biological signaling pathways. Adenylate cyclase is an enzyme that generates cAMP.
The removal of pyrophosphate (PPi) from ATP is necessary for this enzyme to catalyze the conversion of ATP (adenosine triphosphate) into cAMP (cyclic adenosine monophosphate). The enzyme adenylate cyclase can be activated by the compound forskolin found in the roots of Coleus forskohlii.
The cAMP that is created modifies the expression of genes by relaying various signals to transcription factors.
Blood pressure is regulated by cAMP signals, which can also reduce inflammation. cAMP prevents platelet aggregation. This messenger’s signal exhibits beneficial inotropic effects on the heart as well as anti-glaucoma properties.
Cyclic AMP opens ion channels in the cell membrane and activates target enzymes (such as protein kinase A) in the cells. This causes bronchodilation and muscle relaxation.
Scientific study and clinical correlations
a. Studies on extracellular ATP
In response to tissue damage and cellular stress, extracellular levels of adenosine triphosphate (ATP) will rise.
This extracellular ATP enhances tissue repair, encourages the recruitment of immune phagocytes and dendritic cells, and functions as a co-activator of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasomes by activating the P2X and P2Y receptors.
A negative feedback mechanism, however, prevents overreacting immune responses by converting extracellular ATP to adenosine, primarily through the enzymatic activity of the ectonucleotidases CD39 and CD73.
It has been demonstrated that the adenosine in lugs has anti-inflammatory properties that lessen the severity of asthma. In order to lower the risk of this disease, these findings are currently motivating researchers to examine adenosine analogs.
Numerous studies have found elevated adenosine triphosphate (ATP) levels in the erythrocytes of patients with chronic renal failure (CRF), but the mechanism underlying these abnormalities is still under debate.
Purinergic receptors have functions that are conserved and are widely expressed in various tissues, which raises the possibility that ATP and adenosine receptors are involved in the motility of other cell types, including tumor cells.
b. Studies on intracellular ATP
Activation of K+ channel IKs enhances heart function and reduces the rate of heart failure. Scientific findings say that at physiological concentrations, intracellular ATP can act as a signaling molecule to activate the slowly activating K+ channel IKs, which results in the regulation of heart rate adaptation.
The binding of intracellular ATP molecules to the pore-forming α-subunit of IKs, KCNQ1 (channel), stimulated the channel to open.
Congenital mutations in the channel protein reduced the ATP binding or subsequent opening of the IKs channel, these abnormality conditions are related to cardiac arrhythmias in human patients.
Abnormalities in electrical signals are often associated with fatality in cardiovascular diseases, including ischemia and heart failure, in these conditions, cardiac cells have low ATP levels.
This finding stated that increasing intracellular ATP levels in patients with cardiovascular diseases is a new possibility to manage the diseases, and the ATPase provides a unique target for therapies (Yang et al., 2013).
ATP metabolite, adenosine as a signaling molecule
The extracellular adenosine molecule will play both agonistic and antagonistic activity in tumor cells, which is strictly based on the activation of specific receptors.
- Positive role: The extracellular adenosine and its synthetic drug N6-cyclopentyladenosine (CPA) can significantly decrease the tumor size by activating the adenosine A1 receptor (A1AR).
- Negative role: Studies found that Adenosine can also protect tumor cells from Immune destruction by activating the adenosine A2A receptor (A2AAR), which is an agonist receptor in cancer cells. Adenosine can also protect tissues against the negative consequences of hypoxia or ischemia.
Finally, due to the higher negative role of adenosine in tumor cells, scientists finally stated that enhancement of extracellular ATP can activate the inflammasomes, which results in induced anticancer activity. While inhibition of extracellular accumulation of adenosine in tumor cells can reduce the growth of the tumor or induce anticancer activity to minimize the dose of anticancer drugs.
Since ATP is nature’s universal energy currency, recycling phosphorus (a major element of ATP) is a crucial process to maintain the phosphorus levels in living organisms.
Extraction of phosphorus from dead animals and plants and the development of phosphorus-containing fertilizers are established to regulate phosphorus levels.
The phosphorus present in the soil and fertilizers is utilized by plants to produce their own ATP. When we consume plant-related foods, then we metabolize their phosphorus and synthesize our own ATP.
When we expire, our phosphorus goes back into the environment to begin the cycle again.
Frequently Asked Questions
1. What are the three parts of an ATP molecule?
Answer: Adenine, a ribose sugar, and three serially bonded phosphate groups make up the nucleoside triphosphate (nucleoside) structure of ATP.
2. Energy is released from an ATP molecule for cellular processes when it……………….?
Answer: Cells actually draw their energy from the phosphate tail of ATP. The bonds between the phosphates store available energy, which is released when they are broken by the addition of a water molecule (a procedure known as hydrolysis).
- J Stagg & M J Smyth. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene 29(39):5346-58 · September 2010. DOI: 10.1038/onc.2010.292.
- Aton M. Holzer, Richard D. Granstein. Role of Extracellular Adenosine Triphosphate in Human Skin. org/10.1177/120347540400800203.
- Simonetta Falzoni, Giovanna Donvito, Francesco Di Virgilio. Detecting adenosine triphosphate in the pericellular space. The royal sociality, Published 23 April 2013.DOI: 10.1098/rsfs.2012.0101.
- Yang Li, Junyuan Gao, Zhongju Lu, Kelli McFarland, Jingyi Shi, Kevin Bock, Ira S. Cohen, and Jianmin Cui. Intracellular ATP binding is required to activate the slowly activating K+ channel IKs. PNAS Nov, 19, 2013 110 (47) 18922-18927.
- Berger NA. Poly(ADP-ribose) in the cellular response to DNA damage.Radiat Res. 1985 Jan;101(1):4-15
- Verena Katharina Raker, Christian Becker, and Kerstin Steinbrink. The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases. Immunol., 31 March 2016.
- Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science. 1997 Dec 12;278(5345):1907-16. PMID:9417641
- Linder JU, Schultz A, Schultz JE. Adenylyl cyclase Rv1264 from Mycobacterium tuberculosis has an autoinhibitory N-terminal domain. J Biol Chem. 2002 May 3;277(18):15271-6. Epub 2002 Feb 11. PMID:11839758. doi:1074/jbc.M200235200.
- Rickman L, Scott C, Hunt DM, Hutchinson T, Menendez MC, Whalan R, Hinds J, Colston MJ, Green J, Buxton RS. A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol Microbiol. 2005 Jun;56(5):1274-86. PMID:doi:1111/j.1365-958.2005.04609.x