A review on the distribution and biological effects of carnosine and a hypothesis for its biological mechanisms of action are presented. Carnosine and its structural and functional relative, anserine, were found in skeletal muscles at the beginning of the century. Their effects on muscle-working capacity, on the stability of membrane-bound enzymes, as well as their potent immunomodulating property, could not be explained by their pH-buffering capacity or formation of the secondary metabolites histidine and beta-alanine alone. This article suggests that the basis for the biological activities of carnosine and relative compounds is their potent antioxidant and membrane-protecting activity. The plausible chemical mechanism of this activity is discussed, and data regarding the usage of carnosine as a drug for treatment of immunodeficiency are summarized.

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1. The authors compare oxidative injury to brain and kidney Na/K-ATPase using in vitro and in vivo approaches. The substrate dependence of dog kidney Na/K-ATPase was examined both before and after partial hydrogen peroxide modification. A computer simulation model was used for calculating kinetic parameters. 2. The substrate dependence curve for the unmodified endogenous enzyme displayed a typical curve with an intermediate plateau, adequately described by the sum of hyperbolic and sigmoidal components. 3. The modified enzyme demonstrated a dependent curve that closely approximates normal hyperbola. The estimated ATP K(m) value for the endogenous enzyme was about 85 microM; the Kh was equal to 800 microM. The maximal number of protomers interacting was 8. Following oxidative modification, the enzyme substrate dependence curve did not show a significant change in the maximal protomer rate Vm, while the K(m) was increased slightly and interprotomer interaction was abolished. 4. Na/K-ATPase from an ischemic gerbil brain showed a 22% decrease in specific activity. The maximal rate of ATP hydrolysis by an enzyme protomer changed slightly. but the sigmoidal component, characterizing the enzyme's ability to form oligomers was abolished completely. The K(m) value was almost unchanged, but the Hill coefficient fell to 1. These data show that Na/K-ATPase molecules isolated from the ischemic brain have lost the ability to interact with one another. 5. We suggest that the most important consequence of oxidative modification is Na/K-ATPase oligomeric structure formation and subsequent hydrolysis rate suppression.

In order to elucidate the biochemical roles of imidazol-containing dipeptides, we have studied quenching of singlet molecular oxygen (IO2) by carnosine (13-alanyl-L-histidine), its structural components (L-histidine, imidazole, and 13alanine), and related natural free-radical scavengers -L-anserine ([3-alanyl-l-methylhistidine), ergothioneine (2-thiol-L-histidine-betaine), and taurine (2aminoethanesulfonic acid) in aqueous (D20, pD 7) solutions by using monitoring of 102-phosphorescence (1270-nm). The rate constants of IO 2 quenching (Kq) by carnosine, anserine, and ergothioneine were shown to be similar [(3+_l)x107 M-is-l]. Their values resembled those of free L-histidine [Kq=(4_+l)xl07 M-ts -1] and imidazole [Kq=(2_+ l)x 107 M-is-l]. Non-aromatic amino acids -taurine and 13-alanine showed very low quenching activities (Kq<3xl03 M-lc-t). The Kq values did not correlate with the literature data on abilities of the tested compounds to stimulate muscle working capacities and inhibit myeloperoxidase-catalyzed oxygenation. Thus, the dipeptides can be used as potent water-soluble protectors against 10 2 attack whereas their natural biochemical functions are most probably determined by the processes of different nature.

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