Influence of genetic knockout of Pept2 on the in vivo disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice

Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans

“…Since the renal tubular epithelium is equipped with oligopeptide transporters with a high affinity for carnosine (17,34), circulating carnosine can be accumulated by the kidney and may provide an additional exogenous source of protective peptides against diabetic metabolites in patients with low levels of carnosinase.…”

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

“…In line with this hypothesis, renal accumulation of the fluorophore-conjugated dipeptide D-Ala-Lys-AMCA is markedly reduced in kidneys of Pept2-null mice (RubioAliaga et al, 2003). The reabsorption of carnosine (␤-alanyl-L-histidine) is impaired in Pept2-null mice, resulting in an 18-fold increase in the urinary excretion of this chemical (Kamal et al, 2009). Likewise, the total and renal clearance of glycylsarcosine is higher in Pept2-null mice, leading to reduced systemic concentrations and elevated urinary levels (Ocheltree et al, 2005;Frey et al, 2007).…”

Muscle Carnosine Metabolism and β-Alanine Supplementation in Relation to Exercise and Training

“…Carnosine can be transported as an intact dipeptide across the plasma membrane through proton-coupled oligopeptide transporters (PEPT1, PEPT2, PHT) [16][17][18]. Kamal et al [19] have recently shown that the genetic knockout of PEPT2 in mice results in a decreased tissue carnosine content in spleen, kidney and olfactory bulb. Interestingly, the muscle carnosine content was increased rather than decreased in PEPT2 knockout mice, suggesting that release of carnosine from muscle was inhibited by PEPT2 deficiency [19].…”