INDEX

CONTENT PAGE NO.

CELLULAR 5

FUNCTION 6

MECHANISM 10

RELATED TESTING 11

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 CLINICAL SIGNIFICANCE 12

CONCLUSION 13

BIBLIOGRAPHY 13

INTRODUCTION
The body is a complex organism, and as such, it takes energy to maintain proper

functioning. Adenosine triphosphate (ATP) is the source of energy for use and storage at

the cellular level. The structure of ATP is a nucleoside triphosphate, consisting of a

nitrogenous base (adenine), a ribose sugar, and three serially bonded phosphate groups.

ATP is commonly referred to as the "energy currency" of the cell, as it provides readily

releasable energy in the bond between the second and third phosphate groups. In

addition to providing energy, the breakdown of ATP through hydrolysis serves a broad

range of cell functions, including signaling and DNA/RNA synthesis. ATP synthesis

utilizes energy obtained from multiple catabolic mechanisms, including cellular

respiration, beta-oxidation, and ketosis.

The majority of ATP synthesis occurs in cellular respiration within the mitochondrial

matrix: generating approximately thirty-two ATP molecules per molecule of glucose

that is oxidized. ATP is consumed for energy in processes including ion transport,

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muscle contraction, nerve impulse propagation, substrate phosphorylation, and

chemical synthesis. These processes, as well as others, create a high demand for ATP. As

a result, cells within the human body depend upon the hydrolysis of 100 to 150 moles of

ATP per day to ensure proper functioning. In the forthcoming sections, ATP will

undergo further evaluation of its role as a crucial molecule in the daily functioning of

the cell.

Cellular
ATP is an excellent energy storage molecule to use as "currency" due to the phosphate

groups that link through phosphodiester bonds. These bonds are high energy because of

the associated electronegative charges exerting a repelling force between the phosphate

groups. A significant quantity of energy remains stored within the phosphate-phosphate

bonds. Through metabolic processes, ATP becomes hydrolyzed into ADP, or further to

AMP, and free inorganic phosphate groups. The process of ATP hydrolysis to ADP is

energetically favorable, yielding Gibbs-free energy of -7.3 cal/mol.ATP must

continuously undergo replenishment to fuel the ever-working cell. The routine

intracellular concentration of ATP is 1 to 10 uM.Many feedback mechanisms are in

place to ensure the maintenance of a consistent ATP level in the cell. The enhancement

or inhibition of ATP synthase is a common regulatory mechanism. For example, ATP

inhibits phosphofructokinase-1 (PFK1) and pyruvate kinase, two key enzymes in

glycolysis, effectively acting as a negative feedback loop to inhibit glucose breakdown

when there is sufficient cellular ATP.

Conversely, ADP and AMP can activate PFK1 and pyruvate kinase, serving to promote

ATP synthesis in times of high-energy demand. Other systems regulate ATP, such as in

the regulatory mechanisms involved in regulating ATP synthesis in the heart. Novel

experiments have demonstrated that ten-second bursts called mitochondrial flashes can

disrupt ATP production in the heart. During these mitochondrial flashes, the

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mitochondria release reactive oxygen species and effectively pause ATP synthesis. ATP

production inhibition occurs during mitochondrial flashes. During low demand for

energy, when heart muscle cells received sufficient building blocks needed to produce

ATP, mitochondrial flashes were observed more frequently. Alternatively, when energy

demand is high during rapid heart contraction, mitochondrial flashes occurred less

often. These results suggested that during times when substantial amounts of ATP are

needed, mitochondrial flashes occur less frequently to allow for continued ATP

production. Conversely, during times of low energy output, mitochondrial flashes

occurred more regularly and inhibited ATP production.

Function
ATP hydrolysis provides the energy needed for many essential processes in organisms

and cells. These include intracellular signaling, DNA and RNA synthesis, Purinergic

signaling, synaptic signaling, active transport, and muscle contraction. These topics are

not an exhaustive list but include some of the vital roles ATP performs.

ATP in Intracellular Signaling

Signal transduction heavily relies on ATP. ATP can serve as a substrate for kinases, the

most numerous ATP- binding protein. When a kinase phosphorylates a protein, a

signaling cascade can be activated, leading to the modulation of diverse intracellular

signaling pathways.Kinase activity is vital to the cell and, therefore, must be tightly

regulated. The presence of the magnesium ion helps regulate kinase activity. Regulation

is through magnesium ions existing in the cell as a complex with ATP, bound at the

phosphate oxygen centers. In addition to kinase activity, ATP can function as a

ubiquitous trigger of intracellular messenger release. These messengers include

hormones, various-enzymes, lipid mediators, neurotransmitters, nitric oxide, growth

factors, and reactive oxygen species. An example of ATP utilization in intracellular

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signaling can be observed in ATP acting as a substrate for adenylate cyclase. This

process mostly occurs in G-protein coupled receptor signaling pathways. Upon binding

to adenylate cyclase, ATP converts to cyclic AMP, which assists in signaling the release

of calcium from intracellular stores.The cAMP has other roles, including secondary

messengers in hormone signaling cascades, activation of protein kinases, and regulating

the function of ion channels.

DNA/RNA Synthesis

DNA and RNA synthesis requires ATP. ATP is one of four nucleotide-triphosphate

monomers that is necessary during RNA synthesis. DNA synthesis uses a similar

mechanism, except in DNA synthesis, the ATP first becomes transformed by removing

an oxygen atom from the sugar to yield deoxyribonucleotide, dATP.

Purinergic Signaling

Purinergic signaling is a form of extracellular paracrine signaling that is mediated by

purine nucleotides, including ATP. This process commonly entails the activation of

purinergic receptors on cells within proximity, thereby transducing signals to regulate

intracellular processes. ATP is released from vesicular stores and is regulated by IP3

and other common exocytotic regulatory mechanisms. ATP is co-stored and co-released

among neurotransmitters, further supporting the notion that ATP is a necessary

mediator of purinergic neurotransmission in both sympathetic and parasympathetic

nerves. ATP can induce several purinergic responses, including control of autonomic

functions, neural glia interactions, pain, and control of vessel tone.

Neurotransmission

The brain is the highest consumer of ATP in the body, consuming approximately

twenty-five percent of the total energy available.A large amount of energy is spent on

maintaining ion concentrations for proper neuronal signaling and synaptic

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transmission. Synaptic transmission is an energy-demanding process. At the presynaptic

terminal, ATP is required for establishing ion gradients that shuttle neurotransmitters

into vesicles and for priming the vesicles for release through exocytosis.Neuronal

signaling depends on the action potential reaching the presynaptic terminal, signaling

the release of the loaded vesicles. This process depends on ATP restoring the ion

concentration in the axon after each action potential, allowing another signal to occur.

Active transport is responsible for resetting the sodium and potassium ion

concentrations to baseline values after an action potential occurs through the Na/K

ATPase. During this process, one molecule of ATP is hydrolyzed, three sodium ions are

transported out of the cell, and two potassium ions are transported back into the cell,

both of which move against their concentration gradients.

Action potentials traveling down the axon initiate vesicular release upon reaching the

presynaptic terminal. After establishing the ion gradients, the action potentials then

propagate down the axon through the depolarization of the axon, sending a signal

towards the terminal. Approximately one billion sodium ions are necessary to propagate

a single action potential. Neurons will need to hydrolyze nearly one billion ATP

molecules to restore the sodium/potassium ion concentration after each cell

depolarization.Excitatory synapses largely dominate the grey matter of the brain.

Vesicles containing glutamate will be released into the synaptic cleft to activate

postsynaptic excitatory glutaminergic receptors. Loading these molecules requires large

amounts of ATP due to nearly four thousand glutamate molecules stored into a single

vesicle.Significant stores of energy are necessary to initiate the release of the vesicle,

drive the glutamatergic postsynaptic processes, and recycle the vesicle as well as the

left-over glutamate. Therefore, due to the large amounts of energy required for

glutamate packing, mitochondria are close to glutamatergic vesicles.

ATP in Muscle Contraction

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Muscle contraction is a necessary function of everyday life and could not occur without

ATP. There are three primary roles that ATP performs in the action of muscle

contraction. The first is through the generation of force against adjoining actin

filaments through the cycling of myosin cross-bridges. The second is the pumping of

calcium ions from the myoplasm across the sarcoplasmic reticulum against their

concentration gradients using active transport. The third function performed by ATP is

the active transport of sodium and potassium ions across the sarcolemma so that

calcium ions may be released when the input is received. The hydrolysis of ATP drives

each of these processes.

Mechanism
Many processes are capable of producing ATP in the body, depending on the current

metabolic conditions. ATP production can occur in the presence of oxygen from cellular

respiration, beta-oxidation, ketosis, lipid, and protein catabolism, as well as under

anaerobic conditions.

Cellular Respiration

Cellular respiration is the process of catabolizing glucose into acetyl-CoA, producing

high-energy electron carriers that will be oxidized during oxidative phosphorylation,

yielding ATP. During glycolysis, the first step of cellular respiration, one molecule of

glucose breaks down into two pyruvate molecules. During this process, two ATP are

produced through substrate phosphorylation by the enzymes PFK1 and pyruvate

kinase. There is also the production of two reduced NADH electron carrier molecules.

The pyruvate molecules are then oxidized by the pyruvate dehydrogenase complex,

forming an acetyl-CoA molecule. The acetyl-CoA molecule is then fully oxidized to yield

carbon dioxide and reduced electron carriers in the citric acid cycle. Upon completing

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the citric acid cycle, the total yield is two molecules of carbon dioxide, one equivalent of

ATP, three molecules of NADH, and one molecule of FADH2. These high-energy

electron carriers then transfer the electrons to the electron transport chain in which

hydrogen ions (protons) are transferred against their gradient into the inner membrane

space from the mitochondrial matrix. ATP molecules are then synthesized as protons

moving down the electrochemical gradient power ATP synthase.The quantity of ATP

produced varies depending on which electron carrier donated the protons. One NADH

molecule produces two and a half ATP, whereas one FADH2 molecule produces one and

a half ATP molecules.

Beta-Oxidation

Beta-oxidation is another mechanism for ATP synthesis in organisms. During

beta-oxidation, fatty acid chains are permanently shortened, yielding Acetyl-CoA

molecules. Throughout each cycle of beta-oxidation, the fatty acid is reduced by two

carbon lengths, producing one molecule of acetyl-CoA, which can be oxidized in the

citric acid cycle, and one molecule each of NADH and FADH2, which transfer their high

energy electron to the transport chain.

Ketosis

Ketosis is a reaction that yields ATP through the catabolism of ketone bodies. During

ketosis, ketone bodies undergo catabolism to produce energy, generating twenty-two

ATP molecules and two GTP molecules per acetoacetate molecule that becomes oxidized

in the mitochondria.

Anaerobic Respiration

When oxygen is scarce or unavailable during cellular respiration, cells can undergo

anaerobic respiration. During anaerobic conditions, there is a buildup of NADH

molecules due to the inability to oxidize NADH to NAD+, limiting the actions of

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GAPDH and glucose consumption. To maintain homeostatic levels of NADH, pyruvate

is reduced to lactate, yielding the oxidation of one NADH molecule in a process known

as lactic fermentation. In lactic fermentation, the two molecules of NADH created in

glycolysis are oxidized to maintain the NAD+ reservoir. This reaction produces only two

molecules of ATP per molecule of glucose.

Related Testing
Many methods can calculate intracellular ATP levels. A commonly accepted protocol

involves using the firefly luciferase, an enzyme that brings about the oxidation of

luciferin. This reaction is quantifiable due to the energy output of this reaction,

releasing a photon of light, known as bioluminescence, which is quantifiable.

Clinical Significance

ATPs Role in Pain Control

ATP demonstrates a reduction in acute perioperative pain in clinical studies.[20] In

these studies, patients received intravenous ATP. The intravenous adenosine infusion

acts on the A1 adenosine receptor, initiating a signaling cascade that ultimately aids the

pain-relieving effects observed in inflammation. Studies have shown that adenosine

compounds decrease allodynia and hyperalgesia when administered in moderate

doses.A1 adenosine receptor activation renders effective pain intervention due to

delivering a slow onset and a long duration of action, potentially lasting for weeks in

some cases.

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Anesthesia

ATP supplementation produced positive outcomes during anesthesia. Evidence shows

that low doses of adenosine reduce neuropathic pain, ischemic pain, and hyperalgesia to

a level comparable to morphine.Adenosine also decreased postoperative opioid usage,

suggesting a potential long-lasting A1 adenosine receptor activation.

Cardiology and Surgery

ATP has been demonstrated to be a safe and practical pulmonary vasodilator in

patients affected by pulmonary hypertension.Similarly, adenosine and ATP can be

employed during surgery to induce hypotension in patients.

CONCLUSION

“ATP is the fuel of life. It’s an energy currency molecule — the most important source

of chemical and mechanical energy in living systems”.

Therefore, ATP plays a vital role in the biological world. All living cells use Adenosine

Triphosphate molecules as a fuel of energy to survive. Even viruses rely on ATP.

BIBLIOGRAPHY

[PMC free article] [PubMed]

https://www.ncbi.nlm.nih.gov/books/NBK553175/

https://blog.indigoinstruments.com/atp-molecule-monday-the-fuel-of-life/

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