Fructose defect

Defects in Fructose Metabolism Cause Disease (Figure 20-5)... 

Glucose-6-phosphatase defect Fructose-1,6-biphosphatase defect Phosphoenol pyruvate carboxykinase defect... 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

Relationship between Fructose 1,6-Bisphosphatase and Blood Lactate Levels A congenital defect in the liver enzyme fructose 1,6-bisphosphatase results in abnormally high levels of lactate in the blood plasma. Explain. 

Carbohydrate abnormalities, such as renal glycosuria (a transport defect), pentosuria (enzyme deficiency, xylitol dehydrogenase I. lactase deficiencies, fructose intolerance, galactosemia, galacloki-nase deficiency, oxalosis, and several glycogenoses (von Gierke s, Forbes . Andersen s, Hers s. and Tarui s diseases). 

Answer In the liver, lactate is converted to pyruvate and then to glucose by gluconeogenesis (see Figs 14-15, 14-16). This pathway includes the glycolytic bypass step catalyzed by fructose 1,6-bisphosphatase (FBPase-1). A defect in this enzyme would prevent the entry of lactate into the gluconeogenic pathway in hepatocytes, causing lactate to accumulate in the blood. 

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. 

At the present time, commercial isomerization processes based on enzymic catalysis are predominant, so only brief mention will be made of some of the nonenzymic processes that have been considered for commercialization in the past. Probably the major reasons for the current commercial use of enzymic rather than nonenzymic systems are that the nonenzymic systems so far developed result in products having one or more of the following defects too much ash, color, acid, off-flavor, a content of D-mannose or D-psicose, and high ratios of D-glucose to D-fructose. Probably, further advances in our understanding of the isomerization reaction and the mechanisms of the catalysis will lead to more efficient, nonenzymic processes that could replace the enzymic-isomerization systems now used commercially. 

Some strains of L. brevis cause mannitol taint by enzymatic reduction of fructose to mannitol. Mannitol is a polyol produced in heterofermentative metabolism. Its perception is often complicated as it generally exists in wine alongside other defects, but it is usually described as viscous and ester-like, combined with a sweet and irritating finish (Du Toit and Pretorius 2000). Mannitol is usually produced in wines that undergo MLF with a high level of residual sugars still present. 

Wilson s disease, haemochromatosis, galactosaemia, glycogenosis type IV, ai-antitrypsin deficiency, tyrosin-aemia, idiopathic neonatal hepatitis, Niemann-Pick disease, Gaucher s disease, fructose intolerance, defective urea cycle, etc. 

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)... 

This rare and harmless defect is due to a lack of fructokinase. Hereditary Fructose Intolerance... 

Biochemical basis of disorder Because of a genetic disorder, the hepatic aldolase B enzyme is defective, and functions normally in glycolysis but not in fructose metabolism. Glucose production is inhibited by elevated fructose 1-phosphate. When fructose is ingested, severe hypoglycemia results. 

Besides hypoglycemia, D-fructose-induced renal acidification in the HFI defect involves a lowered hydrogen-ion secretory capacity of the proximal nephron, as evidenced by a 20 to 30% diminution in renal-tubular (T) reabsorption of bicarbonate (THCO3) and simultaneous occurrence, and persistence throughout D-fructose administration, of impaired tubular reabsorption of phosphate, cc-amino nitrogen, and uric acid. This abnormality of renal metabolism affects the renal cortex, which contains aldolase B, but does not affect the renal medulla. Thus, the abnormality may result from accumulation of D-fructose 1-phosphate in the renal cortex. The intimate, biochemical mechanism for renal, tubular acidosis is still unknown.164... 

Important disaccharides include lactose and sucrose. Lactose is a disaccharide of p-D-galactose bonded p(l 4) with D-glucose. In galactosemia, defective metabolism of galactose leads to accumulation of a toxic by-product. The ill effects of galactosemia are avoided by exclusion of milk and milk products from the diet of affected infants. Sucrose is a dimer composed of a-D-glucose bonded (al —> p2) with p-D-fructose. 

Lactic acidosis can also result from inhibition of lactate utilization in gluconeoge-nesis (e.g., hereditary fructose intolerance, which is due to a defective aldolase gene). If other pathways that use glucose-6-P are blocked, glucose-6-P can be shunted into glycolysis and lactate production (e.g., glucose 6-phosphatase deficiency). 

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