Acetylcarnosine

Acetylcarnosine
IUPAC name (S)-2-(3-Acetamidopropanoylamino)-3-(1H-imidazol-5-yl)propanoic acid
Other names N-(N-Acetyl-β-alanyl)histidine; N-Acetyl-L-carnosine; N-Acetylcarnosine
Identifiers
Abbreviations	NAC
CAS number	56353-15-2
PubChem	9903482
ChemSpider	8079136 Y
Jmol-3D images	Image 1
SMILES O=C(NCCC(=O)N[C@H](C(=O)O)Cc1cncn1)C
InChI InChI=1S/C11H16N4O4/c1-7(16)13-3-2-10(17)15-9(11(18)19)4-8-5-12-6-14-8/h5-6,9H,2-4H2,1H3,(H,12,14)(H,13,16)(H,15,17)(H,18,19)/t9-/m0/s1 Y Key: BKAYIFDRRZZKNF-VIFPVBQESA-N Y InChI=1/C11H16N4O4/c1-7(16)13-3-2-10(17)15-9(11(18)19)4-8-5-12-6-​14-8/h5-6,9H,2-4H2,1H3,(H,12,14)(H,13,16)(H,15,17)(H,18,19)/t9-/m​0/s1 Key: BKAYIFDRRZZKNF-VIFPVBQEBE
Properties
Molecular formula	C11H16N4O4
Molar mass	268.27 g/mol
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

N-Acetylcarnosine (NAC) is a naturally occurring compound chemically related to the dipeptide carnosine. Its molecular structure is similar to carnosine with the exception that it carries an additional acetyl group.^[1] This makes NAC a more stable molecule which is not easily destroyed by carnosinase, an enzyme that breaks down carnosine to its constituent amino acids, beta-alanine and histidine.

Actions

NAC is a free-radical scavenger and is particularly active against lipid peroxidation in the different parts of the lens in the eye.^[2] It is the active ingredient of eye drops used in order to prevent or treat cataract.

Research

During early experiments performed at the Moscow Helmholtz Research Institute for Eye Diseases, it was shown that NAC (1% concentration), was able to pass from the cornea to the aqueous humour after about 15 to 30 minutes.^[3]

It is believed that NAC is deacetylated (loses its acetyl group) and transforms into carnosine, which then acts as an antioxidant and against glycation.^[4] In another study NAC was reported as effective in improving vision in cataract patients and reduced the appearance of cataract.^[5] The authors called this ‘a snow melting effect’ referring to the slow reduction of the cataractous tissues in the lens following the use of NAC eye drops. Transparency of the lens improved after using NAC eye drops at a concentration of 1% twice a day for four months. These results were relevant to all forms of cataract, mild or severe, although other studies found the most beneficial effect was in relation to early forms of cataract.^[6] This was a landmark study which caused many commercial operators to manufacture their own brands of anti-cataract NAC eye drops.^[7]

Chinese scientists have confirmed that the antioxidant and antiglycating effects of the carnosine molecule can be the reason why it is effective in delaying cataract development.^[8] A recent double-blind, placebo control study confirmed these early findings.^[9]

Statement by the Royal College of Ophthalmologists

The RCO issued the following public statement about N-acetyl carnosine as of August, 2008:

“The evidence for the effectiveness of N-acetyl carnosine eye drops is based on experience on a small number of cases carried out by a Russian researcher team. To date, the research has not been corroborated and the results replicated by others. The long-term effect is unknown. Unfortunately, the evidence to date does not support the 'promising potential' of this drug in cataract reversal. More robust data from well conducted clinical trials on adequate sample sizes will be required to support these claims of efficacy. Furthermore, we do not feel the evidence base for the safety is in any way sufficient to recommend its use in the short term. More research is needed”.^[10]

Since the publication of this statement, the results of new scientific trials have been made available to the Scientific Committee of the RCO.[citation needed]

References

1. ^ Marios Kyriazis (2001). "Low dose L-carnosine". Antiaging Bull 4 (11): 19–24. 
2. ^ Bonnefont-Rousselot D (2001). "Antioxidant and anti-AGE therapeutics". J Soc Biol 195 (4): 391–398. PMID 11938556. 
3. ^ Babizhayev MA, Yermakova VN, Sakina NL et al. (1996). "N alpha acetylcarnosine as a pro-drug of L-carnosine in ophthalmic application as antioxidant". Clin Chim Acta 254 (1-2): 199–121. doi:10.1016/0009-8981(96)06356-5. PMID 8894306. 
4. ^ Boldyrev AA, Dupin AM, Bunin AY et al. (1987). "The antioxidative properties of carnosine, a natural histidine-containing dipeptide". Biochem Int 15 (6): 1105–1113. PMID 3326603. 
5. ^ Babizhayev MA, Deyev AI, Yermakova VN et al. (2002). "Efficacy of N-acetylcarnosine in the treatment of cataracts". Drugs R D 3 (2): 87–103. doi:10.2165/00126839-200203020-00004. PMID 12001824. 
6. ^ Williams DL, Munday P (2006). "The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study". Vet Ophthalmol 9 (5): 311–6. doi:10.1111/j.1463-5224.2006.00492.x. PMID 16939459. 
7. ^ Marios Kyriazis. The Cataract Cure. iUniverse, New York 2005
8. ^ Guo Y, Yan H (2006). "Preventive effect of carnosine on cataract development". Yan Ke Xue Bao 22 (2): 85–8. PMID 17162883. 
9. ^ Babizhayev MA (Oct 2008). "Ocular drug metabolism of the bioactivating antioxidant N-acetylcarnosine for vision in ophthalmic prodrug and codrug design and delivery". Drug Dev Ind Pharm 34 (10): 1071–89. doi:10.1080/03639040801958413. PMID 18777243. 
10. ^ http://www.rcophth.ac.uk/core/core_picker/download.asp?id=177&filetitle=Revised+statement+on+N+Acetyl+Carnosine+for+Cataracts+August+2008