d‐DOPA IS UNIDIRECTIONALLY CONVERTED TO l‐DOPA BY d‐AMINO ACID OXIDASE, FOLLOWED BY DOPA TRANSAMINASE

@article{Wu2006dDOPAIU,
  title={d‐DOPA IS UNIDIRECTIONALLY CONVERTED TO l‐DOPA BY d‐AMINO ACID OXIDASE, FOLLOWED BY DOPA TRANSAMINASE},
  author={Mei Wu and Xiang-jun Zhou and Ryuichi Konno and Yongxiang Wang},
  journal={Clinical and Experimental Pharmacology and Physiology},
  year={2006},
  volume={33}
}
1 Many studies have shown that administration of d‐3, 4‐dihydroxyphenylalanine (d‐dopa) produces contralateral rotation in hemi‐parkinsonian animals comparable to l‐dopa, with less potency and slower onset. It was postulated that d‐dopa was converted to l‐dopa to produce these effects. 2 To investigate the postulated chiral inversion of d‐dopa to l‐dopa and the related mechanism, an enantiomeric separation method for d‐ and l‐dopa using HPLC was first established. Then, rat kidney homogenates… 
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References

SHOWING 1-10 OF 30 REFERENCES
Transamination and other metabolic pathways of 3,4‐dihydroxyphenylpyruvic acid in rats when simultaneously administered with L‐dopa
TLDR
In the rat, 3,4‐dihydroxyphenylpyruvic acid (DHPPA) was shown to be transaminated to L‐dopa when administered orally concomitantly with L‐[3H]dopa, and caused a so‐called L-dopa‐sparing effect, i.e. more administered L‐Dopa reached the circulation and consequently more dopamine reached its target than after administration of L‐ dopa alone.
The effect of simultaneous administration of 3,4‐dihydroxyphenylpyruvic acid and L‐dopa on the bioavailability of L‐dopa in rat and mouse
TLDR
In the rat, administration of 3‐(3,4‐dihydroxy)‐l‐phenylalanine simultaneously with the corresponding α‐keto acid, DHPPA, gives significantly higher concentrations of l‐dopa in the serum and of dopamine and homovanillic acid in the brain than the same dose of l-dopa alone.
Studies on the metabolism of D- and L-isomers of 3,4-dihydroxyphenylalanine (DOPA). VI. Metabolism of D-DOPA in rat kidney.
TLDR
The rat kidney slice had greater activity than the liver slice in metabolizing D-DOPA to dopamine, attributable to the content of D-amino acid oxidase in these organs and may give an explanation of the fact that D- DOPA is metabolized in vivo almost exclusively in the kidney.
Sodium benzoate differentially blocks circling induced by d- and l-dopa in the hemi-parkinsonian rat
d-DOPA and l-DOPA similarly elevate brain dopamine and produce turning behavior in rats
Studies on DOPA Transaminase of Alcaligenes faecalis
TLDR
The pH optima of these enzymes were observed in the alkaline pH range and the enzymes were unstable in the acidic range and inactivated above 60°C and Fe2+, Cu2+, and Al3+ remarkably inhibited the enzyme reaction.
Renal d-Amino Acid Oxidase Mediates Chiral Inversion of NG-Nitro-d-arginine
TLDR
Results reveal a novel pathway of chiral inversion of d-amino acids where the renal DAAO plays an essential role that accounts for the biological activity ofd-NNA.
Role of renal D-amino-acid oxidase in pharmacokinetics of D-leucine.
TLDR
This work examined whether DAO is indispensable for conversion of d-amino acids to their alpha-keto acids by using the stable isotope tracer technique and revealed that DAO was indispensable for the process of chiral inversion ofd-leucine.
The in vivo unidirectional conversion of nitro-D-arginine to nitro-L-arginine.
TLDR
It is found that when D-NA was injected in vivo, its L-enantiomer, L-NA, was found to rapidly appear in plasma samples, and rose to a maximum concentration at 30 min, and remained at this plateau for about 5 h, consistent with the changes in blood pressure.
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