Homocarnosine

Homocarnosine (Figure 31-2), present in human brain at higher levels than carnosine, is synthesized in brain tissue by carnosine synthetase. Serum carnosinase does not hydrolyze homocarnosine. Homocarnosinosis, a rare genetic disorder, is associated with progressive spastic paraplegia and mental retardation. 

The dynamic profile of carnosine was investigated by comparing MD simulations in isotropic solvents (i.e. water and chloroform) with simulation of the compound bound to serum carnosinase (CNl) [22]. This enzyme is characterized by its distribution in plasma and brain, and its ability to hydrolyze also anserine and homocarnosine [23]. The conformational profile of carnosine can be defined by... 

Kohen, R., Yamamoto, Y., Cundy, K.C. and Ames, B.N. (1988). Antioxidant actis itv of carnosine, homocarnosine, and anserine present in muscle and brain. PrcK. Natl Acad. Sci. USA 85, 3175-3179. 

This enzyme [EC 3.4.13.3] (also referred to as Xaa-His dipeptidase, X-His dipeptidase, aminoacylhistidine dipeptidase, and homocarnosinase), is a zinc-dependent dipeptidase that catalyzes the hydrolysis of Xaa-His dipeptides. Carnosine, homocarnosine, and anserine are preferred substrates for this mammalian cytosolic enzyme. Other aminoacylhistidine dipeptides are weaker substrates (including homoanserine). The enzyme is activated by thiols and inhibited by metal-chelating agents. O. W. Griffith (1986) Ann. Rev. Biochem. 55, 855. 

FIGURE 3.1 Structures of carnosine (CAR), N-acetylcarnosine (N-CAR), homocarnosine (HCAR), anserine (ANS), and balanine (BAL). 

Bauer, K. (2005). Carnosine and homocarnosine, the forgotten, enigmatic peptides of the brain. Neurochem. Res. 30,1339-1345. 

Carini, M., Aldini, G., Beretta, G., Arlandini, E., and Facino, R. M. (2003). Acrolein-sequestering ability of endogenous dipeptides Characterization of carnosine and homocarnosine/ acrolein adducts by electrospray ionization tandem mass spectrometry. J. Mass Spectrom. 38,996-1006. 

Kang, J. H., Kim, K. S., Choi, S. Y., Kwon, H. Y., Won, M. H., and Kang, T. C. (2002). Protective effects of carnosine, homocarnosine and anserine against peroxyl radical-mediated Cu,Zn-superoxide dismutase modification. Biochim. Biophys. Acta 1570, 89-96. 

Petroff, O. A., Mattson, R. H., Behar, K. L., Hyder, F., and Rothman, D. L. (1998). Vigabatrin increases human brain homocarnosine and improves seizure control. Ann. Neurol. 44, 948-952. 

Preston, J. P., Hipkiss, A. R., Himsworth, D. J. T., Romero, I. A., and Abbott, J. N. (1998). Toxic effects of beta-amyloid (25-35) on immortalised rat brain endothelial cells Protection by carnosine, homocarnosine and beta-alanine. Neurosci. Lett. 242,105-108. 

Tabakman, R., Jiang, H., Levine, R. A., Kohen, R., and Lazarovici, P. (2004). Apoptotic characteristics of cell death and neuroprotective effect of homocarnosine on pheochro-mocytoma PC12v cells exposed to ischemia. ]. Neurosci. Res. 75, 499-507. 

Petroff, O.A., Hyder, E, Mattson, R.H., and Rothman, D.L. (1999) Topiramate increases brain GABA, homocarnosine, and pyrroli-... 

The internal standard is carboxymethylcysteine(10 mg in 10 mlSSA5%). This should be diluted 1 20 prior to use. Calibration standards containing the usual physiological amino acids may be purchased from Sigma or Pierce. Labile amino acids such as tryptophan, glutamine, asparagine, and homocarnosine should be prepared fresh at each calibration step, but can be stored at -20°C for at least 4 weeks. 

Lysine 3-Methyl-histidine Tryptophan Carnosine Anserine Homocarnosine... 

Homocarnosine is a dipeptide of GABA and L-histidine. After deproteinizing the sample with ethanol, the mixtures are centrifuged. The clear supernatant is evaporated to dryness and derivatized with butanol. The sample is evaporated to dryness and redissolved in the mobile phase. The homocarnosine-butyl derivatives (Fig. 2.3.4) are quantified using liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) operating in the positive mode. With multiple reaction monitoring (MRM), the transitions of m/z 297.0 to m/z 212.0 for homocarnosine and m/z 299.0 to m/z 212.0 for 2H2-L-homocarnosine are quantified. 

Fig. 2.3.4 Formation of the homocarnosine-butyl derivative from homocarnosine and l-butanol...

A calibration curve with aqueous calibrators containing 0, 0.1, 0.5,1.0, and 5.0 nmol homocarnosine are measured. The curve is plotted and results determined. The calibration curve is linear to at least 5.0 nmol. 

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