5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) is an intermediate in the generation of
inosine monophosphate
Inosinic acid or inosine monophosphate (IMP) is a nucleotide (that is, a nucleoside monophosphate). Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in met ...
. AICAR is an
analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
of
adenosine monophosphate
Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine; it is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it t ...
(AMP) that is capable of stimulating
AMP-dependent protein kinase (AMPK) activity. The drug has also been shown as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle.
Mechanism of action
The
nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide ...
form of AICAR,
acadesine, is an analog of
adenosine
Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
that enters cardiac cells to inhibit adenosine kinase and adenosine deaminase. It enhances the rate of
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
re-synthesis increasing adenosine generation from adenosine monophosphate only during conditions of myocardial ischemia. In cardiac
myocytes
A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
, acadesine is phosphorylated to AICAR to activate AMPK without changing the levels of the nucleotides. AICAR is able to enter the
de novo synthesis
In chemistry, ''de novo'' synthesis () refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as the ...
pathway for adenosine synthesis to inhibit adenosine deaminase causing an increase in ATP levels and adenosine levels.
Use as a performance-enhancing drug
In 2009, the
French Anti-Doping Agency
The French Anti-Doping Agency (, AFLD) is an independent public authority formed in 2006 and charged with ensuring that participants in sports in France do not violate rules regarding doping.
As a national anti-doping organization ( NADO), the A ...
, suspected that AICAR had been used in the
2009 Tour de France
The 2009 Tour de France was the 96th edition of the Tour de France, one of cycling's Grand Tours. It started on 4 July in the principality of Monaco with a individual time trial which included a section of the Circuit de Monaco. The race visite ...
for its supposed performance enhancing properties. Although a detection method was reportedly given to the
World Anti-Doping Agency
The World Anti-Doping Agency (WADA; french: Agence mondiale antidopage, AMA) is a foundation initiated by the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against drugs in sports. The agency's key ...
, it was unknown if this method was implemented. As of January 2011, AICAR was officially a banned substance in the World Anti Doping Code, and the standard levels in elite athletes have been determined, to interpret test results.
See also
*
Inosine monophosphate synthase
Bifunctional purine biosynthesis protein PURH is a protein that in humans is encoded by the ''ATIC'' gene.
ATIC encodes an enzyme which generates inosine monophosphate
Inosinic acid or inosine monophosphate (IMP) is a nucleotide (that is, a nu ...
*
Nicotinamide riboside
Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of Vitamin B3, vitamin B3, functioning as a precursor to nicotinamide adenine dinucleotide or NAD+.
Chemistry
While the molecular weight of nicotinamide riboside is 255.25 g/ ...
References
{{Nucleotide metabolism intermediates
Nucleotides
World Anti-Doping Agency prohibited substances