The origin and turnover of D-serine in brain.
The origin of D-serine was investigated using microdialysis probes to administer radiolabeled glucose, glycine, and L-serine directly into rat brain. In these experiments the labeling of D-serine was found to be determined only by the radioactivity present in the L-serine pool, regardless of the precursor employed, indicating that L-serine is the direct precursor of the D-isomer. Its rate of synthesis was 4.6 +/- 1.2 %/h; 9.2 nmol/g/h). This rate of synthesis is in agreement with that found in the mouse after a loading dose of intraperitoneally injected L-[3H]-serine (4.1 %/h). These rates are also consistent with the degradation rates of D-serine in rat and mouse brain, determined in pulse labeling experiments (4.1 and 3.8 %/h, respectively). Synthesis within the brain from L-serine therefore is adequate to account for the turnover of the brain D-serine pool: contributions from other sources, including the diet, must be minimal. Independence from dietary sources was also demonstrated by the failure of labeled D-serine administered in the drinking water to label the brain pool unless very high doses were given. These results suggest that D-serine in the brain is formed directly by the racemization of L-serine.
Dunlop
D S
DS
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA. dunlop@nki.rfmh.org
Neidle
A
A
D000591:Amino Acid Isomerases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D013237:Stereoisomerism
D012694:Serine; D000591:Amino Acid Isomerases; D005947:Glucose; D005998:Glycine