Investigation of a potential role for aldose reductase AlrA in tetrahydropteridine synthesis in Dictyostelium discoideum Ax2

Author:

Kim Hye-Lim1,Ryu Hyun-Chul1,Park Young Shik1

Affiliation:

1. School of Biological Science , Inje University , Gimhae 621-749 , Republic of Korea

Abstract

Abstract Dictyostelium discoideum Ax2 is well-known for the synthesis of d-threo-tetrahydrobiopterin (DH4) with a smaller amount of l-erythro-tetrahydrobiopterin (BH4). DH4 synthesis from 6-pyruvoyltetrahydropterin (PPH4) is catalyzed by aldose reductase (AR)-like protein and sepiapterin reductase (SR) via an intermediate 1′-oxo-2′-d-hydroxypropyl tetrahydropterin, which is non-enzymatically oxidized to d-sepiapterin in the absence of SR. However, l-sepiapterin was a dominant product in the reaction of a cellular extract of spr disrupted in the SR gene. In order to investigate its potential role in tetrahydropteridine synthesis, the enzyme catalyzing l-sepiapterin synthesis from PPH4 was purified from spr . Via mass spectrometry, the protein was identified to be encoded by alrA. AlrA consists of 297 amino acid residues sharing a high sequence identity with human AR. However, in the co-incubation assay, DH4 synthesis was not detected and, furthermore, the recombinant AlrA was observed to suppress BH4 synthesis by SR, which was known to prefer 1′-oxo-2′-d-hydroxypropyl tetrahydropterin to PPH4. Although intracellular DH4 level in alrA was decreased to 60% of the wild type, it is presumed to result from the antioxidant function of DH4. Therefore, despite the structural and catalytic identities with human AR, AlrA seems to be involved in neither BH4, nor DH4 synthesis under normal physiological conditions.

Publisher

Walter de Gruyter GmbH

Subject

Clinical Biochemistry,Molecular Medicine,Biochemistry

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