L-fructose 1-phosphate aldolase

Subsequent action by fructose-l-phosphate aldolase cleaves fructose-l-P in a manner like the fructose bisphosphate aldolase reaction to produce dihy-droxyacetone phosphate and D-glyceraldehyde ... 

Fructose may be phosphorylated to either fructose-6-phosphate, the glycolysis intermediate, or to fructose-1-phosphate, which may be metabolized by a specific fructose-l-phosphate aldolase ... 

DHAP is a glycolysis intermediate, whereas glyceraldehyde must be reduced by a mitochondrial enzyme, glyceraldehyde dehydrogenase, to glycerol, which is then subject to action by glycerol kinase in the liver. The aldolase seems to be the principal pathway of metabolizing fructose and depends on the initial phosphorylation step catalyzed by fructokinase, which produces fructose-l-phosphate. Fructokinase is defective in an inherited disorder, essential fructosuria. Fructose-l-phosphate aldolase is deficient in the hereditary disorder fructose intolerance. 

Hereditary fructose intolerance is caused by an autosomal recessive hereditary defect of the enzyme fructose-l-phosphate aldolase. Whenever fructose is supplied, severe hypoglycaemia and functional disorders occur in the liver, kidneys and CNS. The prevalence is estimated at 1 20,000 births. As with galactose intolerance, the gene which codes aldolase B is also localized on chromosome 9. This enzyme defect causes fructose-l-phosphate to accumulate in the liver and tissue. The cleavage of fructose-1,6-biphosphate is only slightly compromised since the enzymes aldolase A and C are available for this process. The consumption of phosphate and ATP in the tissue results in various functional disorders (i.) inhibition of gluconeogenesis in the liver and kidneys, (2.) increase in lactate in the serum with metabolic acidosis, (3.) decrease in protein synthesis in the liver, and (4.) functional disorders of the proximal tubular cells with development of Fanconi s syndrome, (s. pp 593, 594) (193, 194, 196, 198)... 

See also Fructose, Fructose-l-Phosphate Aldolase B, Fructose Metabolism... 

Fructose-l-phosphate aldolase—fructose-l,6-diphosphate aldolase (Peanasky and... 

One-step Synthesis of L-Fructose Using Rhamnulose-l-phosphate Aldolase in Borate Buffer... 

The synthehc applicability of arsenates is restricted by their toxicity that avoids the green aspect of the enzymatic processes. Wong et al. have shown that the use of inorganic borate buffer allows L-rhamnulose-l-phosphate aldolase (Rha-IPA) to accept DHA as substrate, although the of the reaction is about 50 times lower than with the natural substrate [10]. In spite of this fact, these authors have successfully used this approach for the one-step synthesis of L-fructose and L-rhamnulose, and for the facile two-step synthesis of several L-iminocyclitols. 

The aldehyde substrates may be used as racemic mixtures in many cases, as the aldolase catalyzed reactions can concomitantly accomplish kinetic resolution. For example, when DHAP was combined with d- and L-glyceraldehyde in the presence of FDP aldolase, the reaction proceeded 20 times faster with the D-enantiomer. Fuc 1-P aldolase and Rha 1-P aldolase show kinetic preferences (greater than 19/1) for the L-enantiomer of 2-hydroxy-aldehydes. Alternatively, these reactions may be allowed to equilibrate to the more thermodynamically favored products. This thermodynamic approach is particularly useful when the aldol products can cyclize to the pyranose form. Since the reaction is reversible under thermodynamic conditions, the product with the fewest 1,3-diaxial interactions will predominate. This was demonstrated in the formation of 5-deoxy-5-methyl-fructose-l-phosphate as a minor product (Scheme 5.5).20a 25 The major product, which is thermodynamically more stable, arises from the kinetically less reaction acceptor. 

Fructose-l-phosphate (from fructokinase then cleavage by aldolase B)... 

The four enzymes of the family of dihydroxyacetone phosphate (DHAP)-dependent aldolases fructose-1,6-bisphosphate aldolase (FruA, EC 4.1.2.13), fuculose-1-phosphate aldolase (FucA, EC 4.1.2.17), rhamnulose-1-phosphate aldolase (RhuA, EC 4.1.2.19) and tagatose-1,6-bisphosphate aldolase (TagA, EC 4.1.2.40), catalyze in vivo the reversible asymmetric addition of DHAP to d-glyceraldehyde-3-phosphate (G3P) or L-lactaldehyde, leading to four complementary diastereomers. DHAP-dependent aldolases create two new stereogenic centers, with excellent enantio and diastereoselectivity in many cases. These enzymes are quite specific for the donor substrate DHAP, but accept a wide range of aldehydes as acceptor substrates. There are only two fructose-6-phosphate aldolase isoenzymes reported to be able to use dihydroxyacetone (DHA) as donor substrate (Schiirmann and Sprenger 2001). 

The increased lactate formation during fructose metabolism is probably due to inhibition of diphosphofructose aldolase by accumulation of fructose-l-phosphate. This enzyme is involved in gluconeogenesis as well as in glucose breakdown and its inhibition would channel the metabolism of fructose to pyruvate and lactate. In fact, the lactate formation following xylitol administration was minimal, whereas fructose and sorbitol were nearly equally effective in this respect. 

In our group, a structural variety of N-Cbz-aminoaldehydes were used as acceptor substrates of DHAP-dependent aldolases, namely D-fructose-l,6-phosphate aldolase from rabbit muscle aldolase (RAMA), L-rhamnulose-l-phosphate aldolase (RhuA), and t-fuculose-l-phosphate aldolase (FucA) from Escheridtia coli, for the preparation of structurally diverse pyrrolidine-type iminocyclitols (Scheme 16.2) [16]. 

Fig. 15.2. Pathways of fructose metabolism. 15.4, Fructose-1-phosphate aldolase 15.5, fructose-1,6-diphosphatase 15.7, D-glycerate kinase. F-l-P, Fructose-1-phosphate F-6-P, fructose-6-phosphate F-l,6-DiP, fructose-1,6-diphosphate Glc-6-F, glucose-6-phosphate ATP, adenosine triphosphate ADP, adenosine diphosphate...

Meyerhof, O., Lohmann, K., and Schuster, P., Biochem. Z., 286, 301, 319 (1936). It has recently been reported that the classical crystalline muscle aldolase has no action on fructose-l-phosphate. The reaction described in Fig. 1 is stated to be catalyzed by a 1-phosphofructaldosase found in liver. (Leuthardt, F., Testa, E., and Wolf, H. P., Heh. Chim. Acta 36, 227 (1953).)... 

Pickl, A., Johnsen, U., and Schonheit, P. (2012) Fructose degradation in the haloarchaeon Haloferax volcanii involves a bacterial type phosphoenolpyruvate-dependent phosphotransferase system, fructose-l-phosphate kinase, and class 11 fructose-1,6-bisphosphate aldolase. J Bacteriol 194, 3088-3097. 

A.L Concia, C. Lozano, J.A. Castillo, T. Patella, J. Joglar, P. Qapes, D-Fructose-6-phosphate aldolase in oiganic synthesis cascade chemical-enzymatic preparation of sugar-related poly-hydroxylated compounds, Chem. Eur. J. 15 (2009) 3808-3816. 

Concia, A. L., Lozano, C., Castillo, J. A., Parella, T., Joglar, J., and Clapes, R, D-Fructose-6-phosphate aldolase in organic synthesis Cascade chemical-enzymatic preparation of sugar-related polyhydroxylated compounds. Ghent. Eur. J. 2009,15 (15), 3808-3816. 

Four DHAP converting aldolases are known, these can synthesize different diastereomers with complementary configurations D-fructose (FruA EC 4.1.2.13) and D-tagatose 1,6-bisphos-phate (TagA, F.C 4.1.2.-), L-fuculose (FucA EC 4.1.2.17) and L-rhamnulose 1-phosphate aldolase (RhuA EC 4.1.2.19)3. The synthetic application of the first (class 1 or 2) and the latter two types (class 2) has been examined. 

Franke, D., Machajewski, T., Hsu, C.-C. and Wong, C.-H. (2003) One-pot synthesis of L-fructose using coupled multienzyme systems based on rhamnulose-1-phosphate aldolase. The Journal of Organic Chemistry, 68 (17), 6828-6831. 

Dihydroxyacetone phosphate reacts with D-glycerose in the presence of aldolases of muscle and liver to give D-fructose 1-phosphate (XII) exclusively, whilst DL-glycerose forms equimolar proportions of D-fructose 1-phosphate (XII) and L-sorbose 1-phosphate (XIII).65 Specificity of the enzyme is interesting in the light of Fischer and Baer s observations66 in... 

In this article, the name aldolase is applied to any enzyme preparation that is thought to catalyze an aldol reaction, although it may well be that aldolases differ from one source to another and that many preparations may contain more than one type of aldolase. Thus, the aldolase which splits D-fructose 1-phosphate possibly differs from that which splits D-fructose l,6-diphosphate1M (see Reference 77). 

---