Sepiapterin Reductase and ALR2 (“Aldose Reductase”) from Bovine Brain

Abstract

Sepiapterin reductase (EC 1.1.1.153) catalyses the NADPH-dependent reduction of L-sepiapterin to 7,8-dihydrobiopterin as shown in Fig.1. It was first described in silkworms where it was shown to be a separate enzyme from Dihydrofolate reductase (Matsubara et al., 1963). It has been purified from the livers of various species (Matsubara & Akino, 1964; Matsubara et al., 1966; Katoh, 1971) and a homogeneous enzyme preparation has been obtained from rat erythrocytes (Sueoka and Katoh, 1982; Smith, 1987). It is a dimeric protein with a native relative molecular mass of about 56,000 (rat erythrocytes; Sueoka and Katoh, 1982) and is potently inhibited by N-acetyl derivatives of both serotonin and dopamine such as N-acetylserotonin, melatonin (Katoh et al., 1982,1983), N-methoxyacetylserotonin and N-chloroacetydopamine (Smith et al., 1992) with Ki values in the low micromolar range. Its probable function is in tetrahydrobiopterin (BH4) biosynthesis where it may participate in the reduction of the diketo compound, 6-pyruvoyl-tetrahydropterin (6R-(1′, 2′-dioxopropyl)-tetrahydropterin), to BH4 (see Nichol et al., 1985). It is is unclear whether Sepiapterin reductase alone catalyses the reduction of both keto groups or whether another reductase is also involved. (Milstien & Kaufman, 1989a,b; Steinerstauch et al., 1989). Sepiapterin itself, however, is no longer considered an intermediate in de novo BH4 biosynthesis. Absence of the enzyme could give rise to an atypical form of phenylketonuria (see Niederwieser, 1987). Although Sepiapterin reductase was thought to be specific for the 6-lactoyl side chain of sepiapterin, it was recently found that it has a broad substrate specificity towards carbonyl compounds and can catalyse the NADPH-dependent reduction of many “typical” aldoketo reductase substrates such as p-nitrobenzaldehyde and 9,10-phenanthrenequinone (Katoh & Sueoka, 1984,1989; Sueoka & Katoh, 1985)KeywordsAldose ReductaseBovine BrainHydride TransferAldoketo ReductaseCarbonyl ReductaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.