Fructose 1-phosphate accumulation

The aldolase that cleaves fructose phosphates is deficient. Fructose 1-phosphate accumulates and inhibits glucose production, causing severe hypoglycemia if fructose is ingested. 

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). 

The toxic effect of fluoroacetate was studied in an experiment using intact isolated rat heart. After the heart was perfused with 0.22 mM fluoroacetate, the measured rate of glucose uptake and glycolysis decreased, and glucose 6-phosphate and fructose 6-phosphate accumulated. Examination of the citric acid cycle intermediates revealed that their concentrations were below normal, except for citrate, with a concentration 10 times higher than normal. 

Fructose bisphosphate aldolase (isoenzyme B, M, 156,000) (EC 4.1.2.13). Fructosemia, fructosuria and hypoglucosemia after intake of fructose. Intracellular accumulation of fructose 1-phosphate, Hyperurate-mia. Hepatomegaly. Renal tubular dysfunction. Intraocular bleeding. Patients symptom-free and healthy if fructose avoided. Aldolase A (muscle and most other tissues) and aldolase C (brain and heart) present and fully active. 

Feed-forward control is more likely to be focused on a reaction occurring at or near the end of a pathway. Compounds produced early in the pathway act to enhance the activity of the control enzyme and so prevent a back log of accumulated intermediates just before the control point. An example of feed-forward control is the action of glucose-6-phosphate, fructose-1,6-bisphosphate (F-l,6bisP) and phosphoenol pyruvate (PEP), all of which activate the enzyme pyruvate kinase in glycolysis in the liver. 

Genetic deficiency of fructokinase is benign and often detected incidentally when the urine is checked for glucose with a dipstick. Fructose 1-phosphate aldolase deficiency is a severe disease because of accumulation of fructose 1-phosphate in the liver and renal proximal tubules. Table 1-12-4 compares the two conditions. Symptoms are reversed after removing fructose and sucrose from the diet. 

If at any time only a little ribose 5-phosphate is required for nucleic acid synthesis and other synthetic reactions, it will tend to accumulate and is then converted to fructose 6-phosphate and glyceraldehyde 3-phosphate by the enzymes transketolase and transaldolase. These two products are intermediates of glycolysis. Therefore, these reactions provide a link between the pentose phosphate pathway and glycolysis. The outline reactions are shown below. 

Endogenous hepatosis comprises endogenous metabolic disorders of the liver cell as a rule, the terminology used in this context refers to the accumulated substances (e. g. glycogenosis), the harmful substrate (e.g. fructose-1 phosphate) or the enzyme defect (e.g. apantitrypsin deficiency). 

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)... 

C. Fructose derived from the table sugar (sucrose) would not be converted to fructose 1-phosphate, so it accumulates in the blood and is excreted in the urine, producing a benign fructosuria. 

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