Adenosine is a natural chemical found ubiquitously in every cell of the human body. And it’s an important one: it induces sleep, it controls the circadian rhythm and fine-tunes neurotransmitter levels. In this article, we explore adenosine’s importance to health, factors that increase adenosine, and how the so-called adenosinergic pathway impacts health. What Is Adenosine?
Adenosine is an endogenous nucleoside found in every cell of the body. One of its key roles is to control the sleep-wake cycle. It has a number of other physiological functions, including improving blood flow, protecting the heart, nerves, and other body parts from damage and disease, as well as balancing immune function [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].
Adenosine is sometimes referred to as a “master regulator” because it is involved in such a wide range of activities in the body [ 9 ].
It is also used as a drug , primarily to treat irregular heartbeat (arrhythmias), in addition to pain and high blood pressure in the lungs (pulmonary hypertension) [ 10 , 11 , 12 ].
Owing to these diverse activities, it has critical effects on health and disease. Therefore, researchers have been exploring potential adenosine-receptor-based therapies to treat many different health problems such as infection, autoimmunity, and degenerative diseases since the 1960s [ 7 , 13 , 14 , 15 ]. Enables deep sleep and controls the sleep-wake cycle
Balances immune responses and brain function
Prevents excessive inflammation
Lowers blood pressure
If you’re more interested in adenosine imbalances, their health consequences, and how to lower excessive adenosine activity and levels (especially if you’re constantly tired), take a look at this article . Adenosine Metabolism
As a nucleoside, adenosine is made of an adenine base (a purine) attached to a sugar molecule ( ribose ).
It is formed either inside or on the surface of cells via the breakdown of nucleotides (the basic building blocks of DNA and RNA) or adenine phosphates: energy-rich adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). Under normal conditions, adenosine is created from AMP (by the eventual breakdown of ATP) [ 16 , 17 , 18 ].
Adenosine triphosphate or ATP is known as the body’s “energy currency.” As ATP (energy) decreases, adenosine increases and tells the body to start conserving energy. In other words, adenosine builds up as the body uses up its energy reserves [ 19 , 20 ].
Adenosine acts quickly and is rapidly broken down afterward. When administered intravenously, it has a half-life of around 10 seconds in human blood. Two enzymes break down adenosine [ 21 , 22 ]:
Under normal conditions, adenosine is primarily broken down by ADK, which maintains the relatively low levels of adenosine required by the body on a daily basis [ 9 , 23 ].
ADK breaks adenosine down by to AMP, reducing its levels inside cells. A lack of ADK increases adenosine inside cells and has been associated with diabetes, epilepsy, and cancer. ADK gene mutations cause ADK deficiency, brain damage, and liver failure [ 9 , 24 ].
Meanwhile, ADA is activated when adenosine levels become excessive . It converts adenosine to inosine , which in turn signals to the body to stop producing adenosine [ 9 ].
This process is extremely important because adenosine is required to regulate the immune system and prevent excessive immune reactivity and inflammation [ 25 ]. What Does Adenosine Do?
Adenosine and its receptors are involved in a wide variety of functions, including those of the circadian rhythm and the immune system [ 1 , 2 , 25 ].
This chemical also helps balance blood sugar levels, reduces inflammation and fat production, prevents insulin resistance, and controls body temperature and energy use. Its balanced levels and activity may help prevent diabetes and obesity [ 26 , 27 , 28 , 29 ].
One of the most important functions of adenosine is sleep regulation . Adenosine is produced during both intense physical work and mental work. It slowly builds up in the body over the course of the day, eventually making you sleepy. As adenosine gradually attaches to adenosine receptors, it begins to promote muscle relaxation and tiredness , which is why you start to get tired later in the day [ 30 , 31 ].
After you fall asleep , adenosine molecules start to be broken down . Adenosine needs to be active enough to get you into a state more restorative, deep sleep. Its levels will slowly decrease over the course of the night, eventually waking you up [ 30 , 31 , 2 , 32 , 33 ].
The body also produces adenosine in response to injury, inflammation, inadequate blood supply to an organ (ischemia), and cancer [ 34 ].
Initially, inflammation causes cells to release ATP, ADP, and other nucleotides that trigger a strong immune response. These need to be metabolized into anti-inflammatory adenosine to quell the immune overactivity [ 7 , 35 ].
In other words, ATP first stimulates the immune system and adenosine stops the immune response . However, in cancer and certain immunodeficiency disorders, this stop signal is over-expressed allowing tumors or “opportunistic” infections to hide from the immune system [ 36 ]. Adenosine Receptors
Adenosine has four receptors – A1, A2A, A2B, and A3 – which enable it to achieve such a broad range of activities. Adenosine receptors are important for the everyday functions performed by many tissues in the body, including the brain, heart, and lungs. Adenosine levels determine the type of receptor it will be bind to, which molds the effect it will have on the body [ 37 , 38 , 39 ].
Here’s a rough breakdown of its diverse effects: Sleep: Adenosine increases in the brain during wakefulness and at night, it activates A1 and A2A receptors. This decreases brain activity and promotes sleep [ 40 , 41 , 42 ]. Neurodegenerative diseases: Blocking the A2A receptor can protect the brain from epilepsy, depression , Alzheimer’s disease, and Parkinson’s disease […]