Acetaldehyde from threonine

In various mammalian tissues an enzymatic activity has been reported [451-453] which causes the liberation of glycine 149 and acetaldehyde from L-threonine 150 and has therefore been named threonine aldolase (ThrA EC 4.1.2.5). It is curious that a//o-threonine 151 seems to be a more active substrate for this enzyme than is 150. Cleavage of L-3-phenylserine is also catalyzed by mammalian ThrA enzymes [454-456], which in direction of synthesis nonselec-tively produce both threo (152) and erythro (153) configurated adducts from benzaldehyde and 149 [454], The same enzyme preparations were also able to act on 150. Thus, considerable disagreement still exists in the literature about the true nature of these enzymatic activities. 

Kobayashi (1989) reported the formation of Sotolon in wines by an aldol condensation of acetaldehyde and a-ketobutiric acid (derived from threonine) followed by lactonization (Fig. 7.11). During aging, ethanol is converted into acetaldehyde, thus allowing the formation of Sotolon (Silva Ferreira et ah, 2003). 

Model reactions of this type have been studied in which the catalyst is pyridoxal plus a metal. The enzymatic reactions all appear to use pyridoxal phosphate as a cofactor, and in the case of a bacterial system, Mn" is also required. A major difference between the enzymatic and the model reactions is the requirement for a folic acid cofactor in the former. The formation of glycine and acetaldehyde from L-threonine and L-allo-threonine has been described by Lin and Greenberg. Their partially purified enzyme, threonine aldolase, was not shown to require any cofactors, and the reaction was not reversed. This is in contrast to the results of nonenzymatic experiments in which pyridoxal and a metal catalyze the reversible cleavage of threonine. 

Five-carbon compounds are formed from (S)-aceto-2-hydroxy-butyric acid, also known as (S)-2-ethyl-2-hydroxy-3-oxobutanoic acid, which is the intermediate of isoleucine biosynthesis from threonine. This acid is formed in the reaction of 2-oxobutanoic acid with acetaldehyde and its decarboxylation provides R)-3-hydroxypentane-2-one, which is oxidised to pentane-2,3-dione and reduced to (21 ,31 )-pentane-2,3-diol (Figure 8.13). 

Typical aminocarboxyhc acids, unsaturated fatty acids bound in hpids, sugars and some other food components are precursors of many important sensory-active carbonyl compounds. Amino acids produce aldehydes mainly as secondary products of alco-hohc or lactic acid fermentations and during thermal processes by Strecker degradation. Formaldehyde (methanal) is formed from glycine, acetaldehyde (ethanal) from alanine propanal and butanal arise from threonine (Figure 8.3), 2-methylpropanal from valine. 

The isotope studies of Adelberg led him at first to propose that the formation of isoleucine was initiated by an aldol condensation of a-keto-butyrate (derived from threonine) and acetaldehyde followed by enoliza-tion and hydration 147). This would be susceptible to pinacol rearrange-... 

The product of the PNP enzyme, FDRP 9 has been purified and characterised. The evidence suggests that FDRP 9 is then isomerised to 5-fluoro-5-deoxyribulose-1-phosphate 10, acted upon by an isomerase (Scheme 7). Such ribulose phosphates are well-known products of aldolases and a reverse aldol reaction will clearly generate fluoroacetaldehyde 11. Fluoroacetaldehyde 11 is then converted after oxidation to FAc 1. We have also shown that there is a pyridoxal phosphate (PLP)-dependent enzyme which converts fluoroacetaldehyde 11 and L-threonine 12 to 4-FT 2 and acetaldehyde in a transaldol reaction as shown in Scheme 8. Thus, all of the biosynthetic steps from fluoride ion to FAc 1 and 4-FT 2 can be rationalised as illustrated in Scheme 7. 

Scheme 8. The conversion of L-threonine 12 and fluoroacetaldehyde 11 to 4-FT 2 and acetaldehyde catalysed by the PLP enzyme threonine transaldolase from Streptomyces cattleya [18].

Diacetyl, and its reduction products, acetoin and 2,3-butanediol, are also derived from acetaldehyde (Fig 8D.7), providing additional NADH oxidation steps. Diacetyl, which is formed by the decarboxylation of a-acetolactate, is regulated by valine and threonine availability (Dufour 1989). When assimilable nitrogen is low, valine synthesis is activated. This leads to the formation of a-acetolactate, which can be then transformed into diacetyl via spontaneous oxidative decarboxylation. Because valine uptake is suppressed by threonine, sufficient nitrogen availability represses the formation of diacetyl. Moreover, the final concentration of diacetyl is determined by its possible stepwise reduction to acetoin and 2,3-butanediol, both steps being dependent on NADH availability. Branched-chain aldehydes are formed via the Ehrlich pathway (Fig 8D.7) from precursors formed by combination of acetaldehyde with pyruvic acid and a-ketobutyrate (Fig 8D.7). 

Lrthreonine aldolase (L-threonine acetaldehyde-lyase) catalyzes the reversible condensation of acetaldehyde and glycine to form L-threonine. The enzyme has been shown to be an activity distinct from serine hydroxy-methyltransferase that also catalyzes the above reaction (85,86). The substrate specifically of the adolase has been demonstrated to be flexible with respect to the aldehyde involved. The enzyme has been shown to form phenylserine derivatives from substituted benzaldehydes and glycine (86). 

Hofmann and Schieberle (1996) suggested hydroxyacetaldehyde and 2,3-butanedione as possible precursors of this odorant lactone. A mechanism of formation (in vin jaune ) has been proposed by Guichard et al. (1998) by transformation of threonine (present in coffee) into 2-oxobutyric acid (which can also be derived from carbohydrates), condensation with acetaldehyde and cyclization. 

Three possible mechanisms (Scheme 7) have been discussed to account for stereoselectivity in the formation of [Co(L)3] (L=threonine) from the condensation of acetaldehyde with [Co(gly)3]. Pathway C is shown to be most likely. ... 

There has been a continuing interest in syntheses of 3-amino-2,3,6-trideoxy-hexoses such as daunosamine (9), acosamine (10), etc. In an interesting paper by Fronza et the two sugars have been synthesized from the non-carbohydrate compound (11), which was obtained in 25-30% yield from the incubation of cinnamaldehyde v th acetaldehyde in the presence of bakers yeast (Scheme 2). The crucial amino-lactone (12) was also synthesized from L-threonine. The same authors have also completed their synthesis of A-benzoyl-L-ristosamine (3-benzamido-2,3,6-trideoxy-L /6o-hexose) from 3-benzamido-2,3,6-trideoxy-L-xy/o-hexono-1,5-lactone (Vol. 13, p. 79). An alternative synthesis of methyl A-acetyl-a-L-acosaminide (13) has been described by reduction of the appropriate acetylated oxime by diborane. The thioglycoside (14) was also prepared. ... 

L-Isoleucine originates from 2-oxobutyric acid, a threonine derivative and activated acetaldehyde (C 4) as outlined in Fig. 196. Both compounds condense to form tx-aceto-a-hydroxybutyric acid from which 2,3-dihydroxy-3-methyl-... 

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