Glycolytic enzyme deficiencies erythrocytes

Other pitfalls in correct diagnosis of glycolytic enzyme deficiencies include the red cell age dependency of enzymes such as PK, HK, and G6PD. The measurement of these enzymes simultaneously can give an idea about red cell age and relative deficiencies. Many patients suffering from severe hemolysis have already received blood transfusions. When this occurs, interpreting results from red cell enzyme aissays must be done with great care, since the. presence of donor erythrocytes wdl obscme any deficiencies. In addition, some mutant enzymes display a normal activity in vitro, while in vivo severe hemolysis can occur. More sophisticated assays to measure, for example, heat instability and kinetics have to be used in those cases. 

Effect of pyruvate kinase deficiency Pyruvate kinase deficiency accounts for 95 percent of all inherited defects in glycolytic enzymes. It is restricted to erythrocytes, and causes mild to severe chronic hemolytic anemia. Altered kinetics (for example, increased Km, decreased Vmax, etc.) most often account for the enzyme deficiency. 

The classic function of TPI is to adjust the rapid equilibrium between the two triosephosphates, glycerinealdehyde-3-phosphate and DH AP. Patients with TPI deficiency have unimpressive alterations in glucose utilization, ATP and lactate production. Modeling studies and experimental data suggested that the physiological ATP level was maintained due to the activation of enzymes involved in the pen-tosephosphate and glycolytic pathways (Fig. 8.2) [80, 81]. The interconnection of the two pathways with increased activities can compensate for the reduced TPI activity of deficient cells in TPI-deficient erythrocytes [80, 81]. 

The only pathway that provides ATP in mature erythrocytes is glycolysis. Because these cells lack mitochondria, a nucleus, and other organelles required for protein synthesis, deficiency of glycolytic enzymes may... 

An inborn error of metabolism in which there is a deficiency of pyruvate kinase the glycolytic enzyme which converts phos-phoenolpyruvate to ATP and pyruvate. This deficiency results in a reduced synthesis of ATP and a diminished capacity to cycle NAD in erythrocytes. This results in a haemolytic anaemia. The condition can be diagnosed by measuring the level of the enzyme in erythrocytes. It is inherited as an autosomal recessive. 

In 1965 Japanese workers [128] identified a deficiency in muscle of phosphofructokinase, another glycolytic enzyme the symptoms were quite similar to those of muscle phosphorylase deficiency. The enzyme was also low in erythrocytes. Inheritance is probably autosomal recessive and a small number of other cases have since been reported. A late-onset muscle disorder in two brothers associated with a low activity of phosphohexoseisomerase in the muscle has been reported in another Japanese family [129]. 

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