D-aminoacids

D-Aminoacid oxidase has been isolated from a nnmber of yeasts, and the nucleotide sequence of the enzyme from Rhodotorula gracilis ATCC 26217 has been established (Alonso et al. 1998). The gene could be overexpressed in Escherichia coli, and levels of the enzyme were greater under conditions of low aeration the enzyme isolated from the recombinant organisms was apparently the apoenzyme since maximum activity required the presence of FAD. 

Figure 3.8 The two enantiomers of a-aminoacids. Here we follow the classic nomenclature of l- and D-aminoacids for indicating the two chiral forms. In terms of the S, R nomenclature, L-aminoacids correspond to the S absolute configuration -except for cystein, which is R.

Abstract G72 and G30 constitute a pair of primate-specific genes on complementary strands of human chromosomal 13q33. G72 is proposed to encode a protein that can activate D-amino acid oxidase (DAAO), therefore, named as D-aminoacid oxidase activator (DAOA) (Chumakov et al., 2002). This hypothesis about G72 and DAAO requires substantial further proof (see discussion later), and the neutral name G72 will be used here, although DAOA is widely used in the literature now. The G72/ G30 gene is, at this time, one of the best supported loci for both schizophrenia (SZ) and bipolar disorder (BD) by independent datasets (Craddock et al., 2006 Detera-Wadleigh and McMahon, 2006). Here, we will describe the discovery of gene complex G72/G30, association studies with SZ and BD with a meta-analysis, as well as brief information about the biology of G72/G30. 

List of Abbreviations CD/MRV, Common Disease/Multiple Rare Variants DAAO, D-amino acid oxidase DAOA, D-aminoacid oxidase activator EST, expression sequence tag GEO, Gene Expression Omnibus MAF, minor allele frequency NIMH, National Institute of Mental Health NMDA, N-methyl D-aspartate RT-PCR, reverse transcription-PCR... 

The unique feature of these amphibian skin opioid peptides is the sequence between the important aromatic residues. In contrast to the enkephalins and other mammalian opioid peptides that contain the Gly-Gly dipeptide sequence between Tyr and Phe, the amphibian opioid peptides contain a single D-aminoacid (see Fig. 7.41), which apparently arises from a post-translational conversion of the L-amino acid to its d isomer (665). The identification of these unusual opioid peptides expanded our understanding of the structural requirements for interaction with opioid receptors and provided new lead compounds for further modification (see Sections 6.5.1 and... 

Blass, J., etM. Macheboeuf Sur la presence d aminoacides nouveaux dans... 

E D-aminoacid oxidase, immobilized enzyme from Trigonopsis variables... 

Inhibits catecholase, D-aminoacid oxidase, fatty acid synthesis, lipolysis, nicotinamide deaminase, NMN aminhydrolase, phenol oxidase, tributyrinase. 

Figure 7 Haloaromatic tags decoded structures, a Capital and lower case stand for l-and D-aminoacids respectively.

One of the main problems of oxidases is the equimolar production of hydrogen peroxide as a side-product that can inactivate them or alter its substrate. Thus, the elimination of this compound seems to be a must. Although some metals may destroy hydrogen peroxide, they can also produce some undesired modifications of enzymes or compounds, therefore milder and more selective agents should be preferred. In this sense, the use of catalase (EC 1.11.1.6) is an adequate solution since this enzyme specifically destroys the hydrogen peroxide without producing any other side-reaction. The combined use of oxidases and catalase is then a good solution, as illustrated in Fig 6.4.1. When the enzyme D-aminoacid oxidase is used alone (a), the reaction mainly produces undesired phenylacetic acid, but when used... 

We have also studied complexation of more complex derivatives natural (of the L-series) and unnatural (D-) aminoacids. The association constants (in chloroform-methanol-4 1) were high [ca. 10 M ) but (except of alanine) enantioselectivity was negligible. In DMSO the Kg values were lower by two orders of magnitude but enantioselectivity was very similar again the highest (Kd/Kl) value was noted for alanine. The results are shown in Table 1. 

Lehn, J.-M., and Sirlin, C. "Catalyse Supramoleculaire Conpure des Esters Actives d Aminoacides Lies a un Recepteur Macrocyclique Portant des R sidus Cysteinyles." Noiweau j. Chimie, 11,683-702 (1987). Breslow,... 

More recently we have studied the effects of j3-thia-proline on protein synthesizing systems(56). -Thiapro-line,first synthesized by Eourneau et al. (57) ilia-S not been assayed in biological systems. We have obtained preliminary data indicating that it is a substrate for hog kidney D-aminoacid oxidase and for rat liver mitochondria proline oxidase,two enzymes active on y-thiaproline. 

T.S. Soper and J.M. Manning. "elimination of y -alosubstrates by D aminoacid transaminase associated with inactivation of the enzyme. Trapping of a key intermediate in the reaction. Biochemistry 1978, 17 3377. 

Vedha-Peters, K., Gtmawardana, M., Rozzell, J.D., and Novick, S.J. (2006) Creation of a broad-range and highly stereoselective n-amino add dehydrogenase for the one-step synthesis of D-aminoacids./. Am. Chem. Soc., 128, 10923-10929. 

Les idees traditionelles que nous venons de resumer reposent, en grande partie, sur des conclusions indirectes et des generalisations insuffisamment fondees. Elies ont pour base les donnees de re-cherches qui avaient trait au metabolisme d un nombre restreint d aminoacides encore s agissait-il, bien souvent, du catabolisme d aminoacides non naturels, n ayant pas de rapport aux proteines. 

Cependant, I effet de HONHa sur la formation de groupes amines n est pas trSs regulier parfois I amination du pyruvate n est que faiblement inhibee dans certains cas on observe, au contraire, une depression assez forte de la synthase d aminoacides partir du cetoglutarate, et non seulement du pyruvate (ce qui a alTecte les chiffres moyens du Tableau III). 

L action de la cocaine sur la synthase d aminoacides dans les tis-sus en survie est tr s semblable celle du ffuorac tate et du fluorocit-rate (107) d. la concentration de 5 X 10 M, la cocaine exerce une action inhibitrice tr marqu6e sur la formation d azote amin6 (et de I alanine) dans les essiiis au pyruvate, et n affecte gufere I amination du cetoglutarate (Tableau V). 

---