Aldolase enzyme

Following Its formation D fructose 6 phosphate is converted to its corresponding 1 6 phosphate diester which is then cleaved to two 3 carbon fragments under the mflu ence of the enzyme aldolase... 

This cleavage is a retro aldol reaction It is the reverse of the process by which d fruc tose 1 6 diphosphate would be formed by aldol addition of the enolate of dihydroxy acetone phosphate to d glyceraldehyde 3 phosphate The enzyme aldolase catalyzes both the aldol addition of the two components and m glycolysis the retro aldol cleavage of D fructose 1 6 diphosphate... 

Enzyme Catalyzed. The enzyme aldolases are the most important catalysts for catalyzing carbon-carbon bond formations in nature.248 A multienzyme system has also been developed for forming C-C bonds.249 Recently, an antibody was developed by Schultz and co-workers that can catalyze the retro-aldol reaction and Henry-type reactions.250 These results demonstrate that antibodies can stabilize the aldol transition state but point to the need for improved strategies for enolate formation under aqueous conditions. 

This is interconverted to form glyceraldehyde 3-phosphate and both combine, via the enzyme aldolase, to produce fructose bisphosphate, en route to form glucose or glycogen. 

In Box 10.4 we saw that an aldol-like reaction could be used to rationalize the biochemical conversion of dihydroxyacetone phosphate (nucleophile) and glyceraldehyde 3-phosphate (electrophile) into fructose 1,6-diphosphate by the enzyme aldolase during carbohydrate biosynthesis. The reverse reaction, used in the glycolytic pathway for carbohydrate metabolism, was formulated as a reverse aldol reaction. 

Enzymes are very sophisticated systems that apply sound chemical principles. The side-chains of various amino acids are used to supply the necessary bases and acids to help catalyse the reaction (see Section 13.4). Thus, the enzyme aldolase binds the dihydroxyacetone phosphate substrate by reacting the ketone group with an amine, part of a lysine amino acid residue. This forms an imine that becomes protonated under normal physiological conditions. 

Nature builds up carbohydrate, amino acids, a-hydroxy acids and other molecules by the use of the aldol reaction. The enzyme aldolases are among the most important biocatalysts for C—C bond formation in nature [3]. 

Rose, I. (1981) Chemistry of proton abstraction by glycolytic enzymes (aldolase, isomerases, and pyruvate kinase). Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 293, 131-144. 

At this stage the enzyme aldolase catalyzes the aldol cleavage of fructose 1,6-diphosphate. One product is glyceraldehyde 3-phosphate and the other is... 

On the basis of a catalytic system previously developed by the same group, Nicholls and collaborators [51] reported the preparation of an imprinted polymer for enantioselective formation of a C-C bond with properties of a metallo-enzyme aldolase type II. Polymers were imprinted using the two enantiomers of a 1,3-diketone, the (l.S, 35,45)-(75), and the corresponding (l/ ,3/ ,4/ )-(75), together with two 4-vinyl-pyridine held in place by a Co(II). The cross-aldol condensation... 

Over a decade ago, work on the enzyme aldolase reductase elegantly demonstrated this point. The noncovalent inhibitor alrestatin was modified to contain various electrophiles a-chloroacetamide, a-bromoacetamide or a-iodoacetamide. Noncovalent interactions between inhibitors and protein would not have changed, but molecules behaved differently based on the electrophile the weakest showed reversible inhibition, whereas the iodoacetamide displayed almost complete irreversible inhibition.1401 These results are an important warning if a reaction is too facile, irreversible reactions can obscure true binding affinities. 

Enzymes Aldolases Transketolases Pyrophospho -rylases Glycosyl -transferases Glycosidases... 

The enzyme aldolase catalyzes the addition of a ketone enolate to an aldehyde. 

In the limited sense that this reaction may be viewed as an attack by a nucleophilic species on an aldehyde, it resembles the chemical aldol condensation and the enzymic aldolase condensation. Recent studies of the latter reaction have demonstrated the formation of a l,3-dihydroxy-2-propanone phosphate-aldolase complex, capable of exchanging a carbon-... 

In the following stage, fructose-6-phosphate is phosphorylated again by the action of phosphofructokinase to form fructose-1,6-diphosphate. This reaction also consumes ATP. Later, the enzyme aldolase cleaves to fructose-6-phosphate. As a result of this reaction two triose phosphates are formed dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. This reaction produces a much greater proportion of dihydroxyacetone phosphate (96%), which is rapidly transformed into glycer-aldehyde-3-phosphateby triose phosphate isomerase (Heinisch and Rodicio 1996). 

Standard conditions versus real life. The enzyme aldolase catalyzes the following reaction in the glycolytic pathway ... 

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)... 

STEP 4 Fructose 1,6-bisphosphate is cleaved into two three-carbon pieces by the enzyme aldolase. 

A further example are Laser Raman spectroscopy resonance studies of the enzyme aldolase catalyzing a key reaction in the muscle cells. Zerbi et al.71) investigated resonance Raman spectra of labelled aldolase with argon ion and krypton ion lasers. 

Table 1.7. shows that the proportion of the carbonyl form, in this case ketonic, is much greater with D-fructose and its diphosphate 1.21. In the acyclic form both have a characteristic difunctional group, the hydroxy carbonyl (aldol or ketol). One of the features of this group is its cleavage by a reversible reaction in the presence of purely chemical catalysts. The reaction of the diphosphate 1.21, written according to equation (1.8), is catalysed by the enzyme aldolase, and this is a major pathway to creating carbon-carbon bonds in cells. 

Fructose intolerance A genetic deficiency in the liver enzyme aldolase B. The absence of this enzyme leads to a build up of fructose 1-phosphate and depletion of liver ATP and phosphate stores. 

Fructose 1-phosphate is further metabolized to dihydroxyacetone phosphate (DHAP) and glyceraldehyde by the hepatic isoform of the enzyme aldolase, which catalyzes a reversible aldol condensation reaction. Aldolase is present in three different isoforms. Aldolase A is present in greatest concentrations in the skeletal muscle, whereas the B isoform predominates in the liver, kidney, and intestine. Aldolase C is the brain isoform. Aldolase B has similar activity for either fructose 1,6-bisphosphate (F16BP) or FIP however, the A or C isoforms are only slightly active when FIP is the substrate. 

In the fourth reaction, the fructose i, 6, dispnosphate is split into two 3-carbon fragments by the enzyme aldolase ... 

Boven and Gauch (1966) attribute the fungicidal action of boron compounds to the inhibition of the glycolytic enzyme aldolase. It is conceivable that this inhibition also has a role in the herbicidal activity. On the other hand, the decreased water... 

The speed and specificity of this reaction are ensured by the enzyme aldolase. The product is the sugar fructose-l,6-bisphosphate, which is converted by another enzyme into glucose-l,6-bisphosphate. Removal of the two phosphoryl groups results in a new molecule of glucose for use by the body as an energy source. 

Fructose-l,6-bisphosphate is split into two three-carbon intermediates in a reaction catalyzed by the enzyme aldolase. The products are glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate. 

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