Origin of D-alanine present in urine of mutant mice lacking D-amino-acid oxidase activity

Abstract

Urine of mutant ddY/DAO- mice lacking D-amino-acid oxidase contained 13 times more D-alanine than that of normal ddY/DAO+ mice. Because D-alanine is a component of bacterial cell walls, the possibility that the urinary D-alanine came from intestinal bacteria was examined. In ddY/DAO- mice that were made germ free at birth and reared in a germ-free environment, the quantity of urinary D-alanine was found to be at a low level comparable to that of the normal mice. When these germ-free mice were made gnotobiotic by inoculation with gram-negative bacteria (Escherichia coli and Bacteroides vulgatus), the urinary D-alanine increased to a high level. When these gnotobiotic mice were further inoculated with gram-positive bacteria (Bifidobacterium longum and Eubacterium aerofaciens), the urinary D-alanine increased further. These results indicate that most of the urinary D-alanine of the conventionally reared ddY/DAO- mice is of gastrointestinal bacterial origin.

Creatinine Inhibits <i>D-</i>Amino Acid Oxidase

“…The present investigation showed that CTN inhibited DAO using D-Ala, which may be constantly metabolized by DAO [24], as the substrate, and the inhibition was confirmed by two methods. Although CTN is regarded as an effective indicator of uremia, its toxicity has not been substantiated.…”

Consumption of monosodium glutamate in relation to incidence of overweight in Chinese adults: China Health and Nutrition Survey (CHNS)

“…Although these 2 enantiomers appear to be identical, chiral molecules are fundamentally different. The glutamic acid found in protein is L-glutamic acid only, whereas D-glutamic acid is not found naturally in higher organisms but only in the cell walls of certain bacteria (59)(60)(61). Manufactured or processed free glutamic acid always contains some D-glutamic acid (59,62,63), which is unavailable for peptide and protein synthesis and may even inhibit enzymes.…”

Sensitive Determination of D-Amino Acids in Mammals and the Effect of D-Amino-Acid Oxidase Activity on Their Amounts

“…Because no DAO activity is detected in the frontal brain areas (for example, the cerebrum and hippocampus) of both strains, the difference between the D-Ala amounts in the two strains was not caused by the DAO activities in the corresponding brain areas. Konno et al reported that a large part of D-Ala in the urine of ddY/DAO Ϫ mice was derived from the cell wall of intestinal bacteria, 67) and Nagata et al demonstrated that the amounts of D-Ala in the brains of ddY/DAO Ϫ mice significantly increased after the oral administration of D-Ala. 65) These reports indicate that the amount of D-Ala in the mammalian brain was affected by the D-Ala amount of exogenous origin. In our research, 22) the serum levels of D-Ala were 8.8Ϯ1.4 nmol/ml in the ddY/DAO ϩ mice, and 134.6Ϯ 16.5 nmol/ml in the ddY/DAO Ϫ mice.…”