ラットおよびヒトにおけるL-カルノシンの代謝

抄録

The metabolic fate of L-carnosine in rats was studied after administration of [¹⁴C-U-histidine]-L-carnosine (¹⁴C-(his)-L-carnosine) or [¹⁴C-β-alanine]-L-carnosine (¹⁴C-(ala)-L-carnosine).
1. The blood level of radioactivity reached the maximum concentration (C_max) at 4hr after oral administration of ¹⁴C-(his)-L-carnosine in rats, and the level was almost constant thereafter up to 120hr. On the other hand, the blood levels of radioactivity reached the C_max at 0.5hr after oral administration of ¹⁴C-(ala)-L-carnosine, and declined with a half-life of 3.9hr within the first 6hr and the half-lives in the periods between of 6-24hr and 24-120hr were 19.7hr and 91.9hr, respectively.
2. Male rats excreted 7.9% of administered dose in urine, 6.3% in feces and 37.0% with expired air during 120hr after oral administration of ¹⁴C-(his)-L-carnosine. On the other hand, after administration of ¹⁴C-(ala)-L-carnosine the excretion of radioactivity into the urine, feces and expired air were 5.4%, 1.8% and 80.2%, respectively.
The radioactivity in the carcass after administration of ¹⁴C-(his)-L-carnosine and ¹⁴C-(ala)-L-carnosine were 44.4% and 9.6%, respectively.
3. The blood concentrations and excretion of radioactivity of [¹⁴C-U]-L-carnosine were similar to those after administration of ¹⁴C-(his)-L-carnosine.
4. The disappearance of unchanged L-carnosine in plasma followed first-order kinetics with the half-life of 15min after intravenous administration of ¹⁴C-(his)-L-carnosine to rats, and then the appearance of L-carnosine (the metabolite of L-carnosine) was very rapid and reached the C_max at 0.5hr. When the plasma sample after intravenous administration was treated with sulfosalicylic acid (SSA), the radioactivity of SSA supernatant declined as a function of time.
5. In vitro, L-carnosine was converted to L-histidine in the presence of human plasma within 15min at room temperature.
6. The present studies indicade that L-carnosine was converted to L-histidine and β-alanine in rats and humans, of which L-histidine was further utilized for the incorporation of endogenous high molecular substances.