Glycolytic enzymes liver

The pathway for gluconeogenesis is shown in Figures 6.23 and 6.24. Some of the reactions are catalysed by the glycolytic enzymes i.e. they are the near-equilibrium. The non-equilibrium reactions of glycolysis are those catalysed by hexokinase (or glucokinase, in the liver), phosphofructokinase and pyruvate kinase and, in order to reverse these steps, separate and distinct non-equilibrium reactions are required in the gluconeogenic pathway. These reactions are ... 

Glucose is converted to triose phosphate via the enzyme glucokinase and other glycolytic enzymes in the liver. Amino acids are converted to oxoacids by pathways described in Chapter 8. 

Brune and Lapetina (1989) reported that NO could activate a platelet ADP-ribosyltransferase that resulted in the ribosylation of a 39 kDa protein. Subsequent work revealed that the protein was glyceraldehyde phosphate dehydrogenase (GAP-DH), and that ribosylation was associated with reduced GAP-DH activity (Dimmeler et al., 1992). In our collaboration with Molina et al., (1992), we have shown that GAP-DH activity is dramatically inhibited in C. parvum treated rats and that this action is associated with both a ribosylation and nitro-sylation of the enzyme. Such a marked inhibition of a glycolytic enzyme could explain some of the metabolic changes observed in the liver in sepsis. 

Seven of the reactions of glycolysis are reversible and are used for gluconeogenesis in the liver and kidneys. Three reactions are physiologically irreversible and must be circum vented. These reactions are catalyzed by the glycolytic enzymes pyruvate kinase, phos phofructokinase, and hexokinase. 

Gregus, Z. and Nemeti, B. (2005) The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase works as an arsenate reductase in human red blood cells and rat liver cytosol. Toxicological Sciences, 85(2), 859-69. 

HIF 1 REGULATION OF GENES FOR LIVER-SPECIFIC GLYCOLYTIC ENZYMES... 

Diphosphofructoaldolase is a soluble glycolytic enzyme especially abundant in skeletal muscle, occurring also in the myocardium and to a lesser extent in liver and erythrocytes, so that hemolysis of blood specimens elevates the serum aldolase activity and must therefore be avoided. The molecular weight of muscle aldolase is 147,000-180,000 (DIO), Its function is specifically the reversible splitting of D-fructose-1,6-diphosphate (FDP) into equimolecular amounts of the trioses D-glyceralde-hyde-3-phosphate (G-3-P) and dihydroxyacetone phosphate (DAP). 

Adenylate kinase, which is abundant in muscle as in many other tissues, decreases in dystrophic mouse and human muscle (H6, P7). This enzyme, by interconverting adenine nucleotides, probably functions in the control of glycolysis it seems reasonable to suppose, therefore, that its activity may be governed by the same factors which influence glycolytic enzymes, as discussed above. A severe decline in the activity of AMP deaminase occurs in muscular dystrophy (P6, P7) and also in denervated muscle (M12) and in some cases of muscle affected by hypokalemic periodic paralysis (E6). Skeletal muscle normally contains a higher concentration of this enzyme than other tissues in fact, it is almost absent from some, such as liver. Its physiological function, and hence the significance of the sharp decline in its activity in diseased muscle, is still a matter of speculation. 

Another effect of glucagon binding to liver cells is the inactivation of the glycolytic enzyme pyruvate kinase. (Protein kinase C, an enzyme activated by cAMP, converts pyruvate kinase to its inactive phosphorylated conformation.) Hormones also influence gluconeogenesis by altering enzyme synthesis. For example, the synthesis of gluconeogenic enzymes is stimulated by cortisol (a steroid hormone... 

The liver is the major site of biosynthetic reactions in the body. In addition to those pathways mentioned previously, the liver synthesizes fatty acids from the pymvate generated by glycolysis. It also synthesizes glucose from lactate, glycerol 3-phosphate, and amino acids in the gluconeogenic pathway, which is principally a reversal of glycolysis. Consequently, in liver, many of the glycolytic enzymes exist as isoenzymes with properties suited for these functions. 

In addition to stimulating the synthesis and release of LPL, insulin stimulates glucose metabolism in adipose cells. Insulin leads to the activation of the glycolytic enzyme phosphofructokinase-1 by an activation of PFK-2, which increases fructose 2,6-bisphosphate levels. Insulin also stimulates the dephosphorylation of pyruvate dehydrogenase, so that the pyruvate produced by glycolysis can be oxidized in the TCA cycle. Furthermore, insulin stimulates the conversion of glucose to fatty acids in adipose cells, although the liver is the major site of fatty acid synthesis in humans. 

All glycolytic enzymes are increased in amount during carcinogenesis (37, 346). Glucokinase is increased to 570% of its control value in the liver of animals exposed to the carcinogen 3 -methyl-4-dimethylaminoazobenzene (12). 

Some cellular biochemical constituents, such as DNA and the glycolytic enzymes, are found in every cell, while others (pepsin) are limited to a few. The particular mosaic formed is an expression of differentiation. Among cellular components, those common to all cells have been most extensively investigated. The biochemical cytology of only liver tissue has been studied on a large scale, and much of our knowledge of cellular components is based on information gathered from it. 

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