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 ...

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 substit ...

(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 nucleoti ...

form of AICAR,

acadesine Acadesine (INN), also known as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, AICA-riboside, and AICAR, is an AMP-activated protein kinase activator which is used for the treatment of acute lymphoblastic leukemia and may have applications ...

, 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 biomolecu ...

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 ...

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 ...

, 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 visit ...

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.

References

{{Nucleotide metabolism intermediates Nucleotides World Anti-Doping Agency prohibited substances

Mechanism of action

Use as a performance-enhancing drug

See also

References