Glycolysis enzyme deficiencies

Deficiencies of enzymes involved in glycolysis, the hexose monophosphate pathway, the closely related glutathione metabolism and synthesis, and nucleotide metabolism have emerged as causes of hereditary nonspherocytic hemolytic anemias (Table 1) (F10, Fll, M27). Some enzyme deficiencies, such as diphospho-glycerate mutase deficiency, lactate dehydrogenase deficiency, and NADH cy-... 

H. G. Holzhtitter, G. Jacobasch, and A. Bisdorff, Mathematical modeling of metabolic pathways affected by an enzyme deficiency. A mathematical model of glycolysis in normal and pyruvate kinase deficient red blood cells. Eur. J. Biochem. 149(1), 101 111 (1985). 

Phosphofructokinase is the enzyme deficient in glycolysis leading to glycogenosis type VII (GSD VII, M. Tarui, MIM 232 800). The enzyme in its active form is a tetra-mer, composed of three different subunits M (muscle), L (liver), and P or F (platelets, fibroblasts). The enzyme is found in different compositions in different tissues, as shown in Table 4.6.16. In glycogenosis type VII the enzyme deficiency can only be determined in muscle, because only the deficiency of the M form leads to GSD VII. 

A different problem results from deficiency of enzymes of glycolysis such as phosphofructokinase (see Box 20-D), phosphoglycerate rnutase, and pyruvate kinase. Lack of one isoenzyme of phosphoglycerate rnutase in muscle leads to intolerance to strenuous exercise/ A deficiency in pyruvate kinase is one of the most common defects of glycolysis in erythrocytes and leads to a shortened erythrocyte lifetime and hereditary hemolytic anemia.s... 

Case B (c) Galactose 1-phosphate uridylyltransferase is an enzyme involved in conversion of galactose to glucose, which then can enter glycolysis. Absence of this enzyme leads to accumulation of galactose in the blood and excretion in the urine. A patient with this deficiency should be on a low-lactose diet (treatment 3). 

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. 

Phosphoglycerate mutase deficiency, the eighth enzyme step of glycolysis, is inherited autosomal recessive. Onset occurs in childhood to early adulthood. Symptoms include exercise intolerance, cramps, muscle pain and sometimes myoglobinuria. 

MetabolicaUy, biotin is of central importance in lipogenesis, gluconeogen-esis, and the catabolism of branched-chain (and other) amino acids. There are two well-characterized biotin-responsive inborn errors of metabolism, which are fatal if untreated holocarboxylase synthetase deficiency and biotinidase deficiency. In addition, biotin induces a number of enzymes, including glu-cokinase and other key enzymes of glycolysis. Biotinylation of histones may be important in regulation of the cell cycle. 

Biotin acts to induce glucokinase, phosphofructokinase, and pyruvate kinase (key enzymes of glycolysis), phosphoenolpyruvate carboxykinase (a key enzyme of gluconeogenesis), and holocarboxylase synthetase, acting via a cell-surface receptor linked to formation of cGMP and increased activity of RNA polymerase. The activity of holocarboxylase synthetase (Section 11.2.2) falls in experimental biotin deficiency and increases with a parallel increase in... 

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