Fructose-l-phosphate

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 intolerance is a condition showing a number of close similarities to galactosemia (F3, W5). It has been shown that, in fructose intolerance, fructose-l-phosphate accumulates and inhibits a number of enzymes. Marked hypoglucosemia follows ingestion of fructose, but insulin is almost certainly not involved (FI, P10). 

Table 4.6.7 Pathological values of fructose-l-phosphate and fructose-1,6-bisphosphate in patients with hereditary fructose intolerance (HFI) [36]...

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. 

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. 

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)... 

H3. Hers, H. G., and Kusacka, T., Le metabolisme du fructose-l-phosphate dans le foie. Biochem. et Biophys. Acta 11, 427 (1953). 

Fructose is acted on by the enzyme fructokinase to produce fructose-l-phosphate. 

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

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

Fig. 46.7. Regulation of glucokinase by regulatory protein (RP). RP is localized to the nucleus, and in the absence of glucose or presence of fructose 6-phosphate, most glucokinase is translocated to the nucleus and binds RP. This leads to the formation of the inactive form of glucokinase. When glucose or fructose-l-phosphate levels rise, glucokinase is released from RP. It then translocates to the cytoplasm and actively converts glucose to glucose 6-phosphate.

Sorbitol is metabolized by the liver (Fig. 1) and oxidized to fructose by the enzyme sorbitol dehydrogenase in the course of which reaction NAD is reduced (Fig. 1), Fructose is then phos-phorylated to form fructose-l-phosphate by hepatic phosphofructo-kinase in a reaction requiring ATP. Through the action of hepatic 1-phosphofructoaldolase, the fructose-l-phosphate yields dihydrox-yacetonephosphate and glyceraldehyde. While dihydroxyacetonephos-... 

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. 

Fructose-l-phosphate Metabolism. A kinase in mammalian liver has been found to phosphorylate fructose on carbon l. This is in contrast to... 

Hexokinase transfers a phosphate group from ATP to glucose with the formation of glucose-6-phosphate, and fructohexokinase performs the same transfer to fructose forming fructose-l-phosphate. The transphosphorylases can be divided into several types according to the magnitude of JF for the transfer reaction. 

During a sojourn in St. Louis of about a year and a half, Ochoa extended previous studies on carboxylase and worked on the relation between glycolysis and phosphorylation. Also, in collaboration with the Coris, he isolated and characterized fructose-l-phosphate and inorganic pyrophosphate in liver dispersions. In St. Louis he was imbued with the importance and the techniques of isolating and characterizing enzymes. 

The disaccharide sucrose is imported by a specific phosphotransferase system PTSjuc responsible for uptake and phosphorylation of sucrose [125], yielding sucrose-6-phosphate. Sucrose-6-phosphate hydrolase then yields glucose-6-phosphate and free fructose [107, 127]. Fructose is exported out of the C. glutamicum cell and re-imported by PTSf, with concomitant phosphorylation to fructose-l-phosphate [128]. Overexpression of the fructose bisphosphatase genefbp improved L-lysine product yields on sucrose [46]. 

Rat liver extracts also contain two highly specific kinases, namely, glucokinase and fructokinase. Glucokinase, in the presence of ATP and Mg++, forms glucose-6-phosphate fructokinase catalyzes the formation of fructose-l-phosphate. Beef Uver fructokinase, like rat fiver fructokinase, is strongly activated by potassium chloride. Sodium and ammonium ions are relatively inert. The affinity of the enzyme for fructose is very high, the Km being lower than 5 X 10 moles per liter. This is in contrast to muscle fructokinase, which has a very weak aflfinity for its subtrate. 

In rat liver, the phosphorylation of fructose by means of ATP occurs at a greater rate than that of glucose. It is inferred that fructokinase predominates in this tissue, and this is supported by the observation that the anaerobic degradation of glucose by rat liver slices is relatively slow. An active fructokinase has been isolated from this tissue, and in contrast to yeast hexokinase, phosphorylates at Ci. The product, fructose-1-phosphate, had previously been isolated after autolysis of liver, during fructose utilization in liver or intestine, or after enzymatic hydrolysis of fructose 1,6-diphosphate by bone phosphatase. It may be noted that both fructose-l-phosphate and fructose-6-phosphate are formed in the latter procedure. The phosphate linkage at Ci is far more labile to acid than is that at Ce. 

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).)... 

In the phosphorylation of fructose by inorganic phosphate and alkaline phosphatase, the major ester formed is stated to be fructose-l-phosphate. Meyerhof and Green have concluded that the 1-phosphate bond possesses less energy than the 6-phosphate bond. Alkaline phosphatase also trans-phosphorylates from creatine phosphate to form the fructose phosphates. ... 

It has been demonstrated that muscle extracts contain a specific phosphofructokinase which catalyzes the formation of fructose-1,6-diphosphate from fructose-l-phosphate (reaction 2). 

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