Carnosine synthetase

The P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

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 second example of property space applications concerns the dipephde camo-sine (P-alanine-L-histidine, see Fig. 1.4) which represents the archetype of a series of histidine-containing dipeptides whose full physiological role remains poorly understood despite extensive studies in recent years [18-20]. Carnosine is synthesized by carnosine synthetase and hydrolyzed by dipeptidases (also called camosi-nases) which belong to the metalloproteases [21]. 

ASPARAGINE SYNTHETASE CARNOSINE SYNTHETASE LEUCYL-tRNA SYNTHETASE... 

CARNOSINE SYNTHETASE CHAPERONES CHOLINE KINASE CHOLOYL-CoA SYNTHETASE COBALAMIN ADENOSYLTRANSFERASE 4-COUMAROYL-CoA SYNTHETASE CREATINE KINASE CTP SYNTHETASE CYTIDYLATE KINASE 2-DEHYDRO-3-DEOXYGLUCONOKINASE DEHYDROGLUCONOKINASE DEOXYADENOSINE KINASE DEOXYADENYLATE KINASE DEOXYCYTIDINE KINASE (DEOXYjNUCLEOSIDE MONOPHOSPHATE KINASE DEOXYTHYMIDINE KINASE DEPHOSPHO-CoA KINASE DETHIOBIOTIN SYNTHASE DIACYLGLYCEROL KINASE DIHYDROFOLATE SYNTHETASE DNA GYRASES DNA REVERSE GYRASE ETHANOLAMINE KINASE EXONUCLEASE V... 

CARNITINE O-ACETYLTRANSFERASE CARNITINE O-OCTANOYLTRANSFERASE CARNITINE O-PALMITOYLTRANSFERASE CARNOSINASE CARNOSINE SYNTHETASE CARNOT CYCLE... 

Intracellular carnosine concentration may be subject to metabolic regulation. Destruction of the dipeptide by camosinase is stimulated by citrate (Vistoli et al., 2006), thus raising the possibility that inhibitory molecules could be created to prevent destruction of the dipeptide in sera. Camosine s synthesis by carnosine synthetase is downregulated by raised cAMP levels (Schulz et al., 1989), at least in astrocytes. Thus, high glucose concentrations could lower cAMP levels and hence stimulate carnosine synthesis. 

M.R.G. Wood and P. Johnson, Purification of carnosine synthetase from avian muscle by affinity chromatography and determination of its subunit structure. Biochim. Biophys.. Acta, 662 (1981) 138-144. 

Margolis FL, Grillo M, Hempstead J, Morgan JI. 1987. Monoclonal antibodies to mammalian carnosine synthetase. J Neurochem 48 593-600,... 

The rat brain carnosine synthetase required DPN, which was used in the overall reaction at a 5.5/1 ratio carnosine/DPN (Skaper et al. 1973). 

Deleterious protein cross-linking can also be induced by reactive nitrogen species (RNS) such as peroxynitrite ONOO formed by the reaction of superoxide with nitric oxide (NO). The cross-links are formed between tyrosine residues following nitration by peroxynitrite (Sitte, 2003). Carnosine appears to play roles not only in NO generation but also in protection against excess NO production by inducible nitric oxide synthetase (NOS), thereby preventing ONOO-mediated protein modification (Fontana et ah, 2002). Evidence for a carnosine-NO adduct has also been published (Nicoletti et al., 2007). 

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